COMPOSITIONS AND METHODS FOR MODULATING CGRP SIGNALING TO REGULATE INTESTINAL INNATE LYMPHOID CELLS

REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

The contents of the electronic sequence listing (BROD_4040_ST25.txt”; Size is 9,000 Kilobytes and it was created on Mar. 13, 2020) is herein incorporated by reference in its entirety.

TECHNICAL FIELD

The subject matter disclosed herein is generally directed to compositions and methods for modulating intestinal ILC2 cells and responses by targeting CGRP signaling.

BACKGROUND

The immune system in the small intestine is comprised of a complex network of innate and adaptive components that sense and respond antigens from the diet, commensal microbiota and pathogens. Dysregulated immune reactions often lead to chronic inflammatory responses, including type 2 inflammation (Gieseck et al., 2018; Hammad and Lambrecht, 2015; Pulendran and Artis, 2012), which in turn plays a key underlying role in several unrelenting inflammatory diseases, including food allergy (Locksley, 2010; Tordesillas et al., 2017).

Type 2 inflammation is characterized by the production of the cytokines interleukin-4 (IL-4), IL-5, IL-13 and IgE antibody, and tightly regulated and coordinated responses across cell types, including T helper 2 (Th2) cells, B cells, dendritic cells (DCs) and mast cells. In particular, ILC2s have emerged as key regulators of tissue homeostasis and type 2 inflammation (Artis and Spits, 2015; Kotas and Locksley, 2018), and form the prominent source of type 2 cytokines at its early stages (Molofsky et al., 2015; Neill et al., 2010; Price et al., 2010). While the core transcriptional program of ILCs maintains their cellular identity and homeostatic type 2 cytokine competency (Ricardo-Gonzalez et al., 2018), their activity in the intestines is shaped by tissue-specific signals, including activation by IL-25 produced by Tuft cells (von Moltke et al., 2016), and suppression by micronutrients (Spencer et al., 2014).

Despite these substantial advances, our understanding of cellular participants in type 2 inflammation, the mechanisms that maintain homeostasis and induce inflammation, and which additional cell types, besides immune cells, may participate in this cellular circuit in the small intestines is incomplete. Single-cell RNA-seq (scRNA-seq) can dissect cellular diversity on a large scale (Tanay and Regev, 2017; Wagner et al., 2016) and identify cell states of individual cell types in response to different stimuli (Bielecki et al., 2018; Haber et al., 2017). For example, scRNA-seq of lung ILCs recently revealed that neuronal-derived Neuromedin U (NMU) amplifies ILC2 activity in allergic inflammation (Wallrapp et al., 2017), and the same neuron-immune circuit was also shown to induce activation of ILC2s in the small intestine (Cardoso et al., 2017; Klose et al., 2017). Given the increased prevalence and epidemic rise in allergy and asthma in the last two decades, identifying the molecular pathways that regulate ILC2s during allergic responses is an important area of inquiry.

Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.

SUMMARY

In one aspect, the present invention provides for a method of maintaining or inducing homeostasis of intestinal ILC2 cells in a subject at risk for or having aberrant activation and expansion of the intestinal ILC2 cells comprising administering CGRP to the subject. In certain embodiments, the aberrant activation and expansion of the intestinal ILC2 cells is induced by IL-25. In certain embodiments, the CGRP is administered intravenously, intraperitoneally, intragastrically, or orally. In certain embodiments, the subject has an allergy or history of allergic symptoms. In certain embodiments, the allergy is a food allergy. In certain embodiments, the allergy is caused by an allergen that induces epithelial cells in the gut to release IL-25. In certain embodiments, CGRP is administered after the subject has contacted or ingested an allergen. In certain embodiments, the CGRP is administered before an inflammatory response. In certain embodiments, CGRP is administered upon detecting an inflammatory response. In certain embodiments, the subject does not have an infection, such as a helminth infection. In certain embodiments, the method further comprises administering to the gut of the subject one or more agents capable of modulating expression, activity or function of one or more genes selected from the group consisting of: Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5. In certain embodiments, CGRP induces expression of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5 to maintain homeostasis of intestinal ILC2 cells. Thus, in intestinal ILC2s, treatment with CGRP increases the expression of one or more of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5, and a combination treatment may provide for prevention of aberrant intestinal ILC2 inflammatory responses. In certain embodiments, the method comprises activating a cAMP response module, wherein the cAMP module comprises one or more genes selected from the group consisting of Adrb2, Adora2a, Pde4b, Akap12, Areg, Crem and Il5. In certain embodiments, the one or more agents comprises an adenylate cyclase activator. In certain embodiments, the agent is forskolin. In certain embodiments, the one or more agents comprises an agonist of PD-1. In certain embodiments, the one or more agents comprises an agonist of GPR65.

In another aspect, the present invention provides for a method of maintaining or inducing homeostasis of intestinal ILC2 cells in a subject at risk for or having aberrant activation and expansion of the intestinal ILC2 cells comprising administering to the gut of the subject one or more agents capable of modulating expression, activity or function of one or more genes selected from the group consisting of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5. In certain embodiments, CGRP induces expression of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5 to maintain homeostasis of intestinal ILC2 cells. Thus, in intestinal ILC2s, increasing the expression, activity or function of one or more of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5 may provide for prevention of aberrant intestinal ILC2 inflammatory responses. In certain embodiments, the method comprises activating a cAMP response module, wherein the cAMP module comprises one or more genes selected from the group consisting of Adrb2, Adora2a, Pde4b, Akap12, Areg, Crem and Il5. In certain embodiments, the one or more agents comprises an adenylate cyclase activator. In certain embodiments, the agent is forskolin. In certain embodiments, the one or more agents comprises an agonist of PD-1. In certain embodiments, the one or more agents comprises an agonist of GPR65. In certain embodiments, the subject has an allergy or history of allergic symptoms. In certain embodiments, the allergy is a food allergy. In certain embodiments, the allergy is caused by an allergen that induces epithelial cells in the gut to release IL-25. In certain embodiments, the subject does not have an infection, such as a helminth infection.

In another aspect, the present invention provides for a method of modulating an ILC2 inflammatory response comprising administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity or function of one or more biological programs characterized by ILC Topic 2, myeloid cell Topic 1, T cell Topic 5 or stromal cell Topic 4, wherein ILC Topic 2 comprises one or more genes or polypeptides selected from the group consisting of Calca, Hs3st1, Areg, Il13, Il4, Ccl1, Hes1, Il17rb, Lgals7, Homer2, Il5, Gata3, Deptor, Ptpn13, Ly6a, Hba-a1, Kcnn4, Ccr4, Rxrg, Sub1, 1700061F12Rik, Cntnap2, AA467197, Ptgir, Il10, Nfkb1, Lmo4, Pparg, Plaur, Il9r, Serpine1, Scel, Bmp7, Neb, Sox8, Lpcat2, Samsn1, Alox5, Gpr65, Abhd17c, Gm20186, Gm973, Epas1, Ccr8, D430036J16Rik, Cd6, Stxbp6, 9230102O04Rik, Furin and Klf5, wherein myeloid cell Topic 1 comprises one or more genes or polypeptides selected from the group consisting of Cpa3, Cma1, Mcpt4, Tpsb2, Fcer1a, Hs3st1, Gata2, Cited4, Cyp11a1, Tph1, Furin, Rab27b, Slc45a3, Ccl1, Il13, Il1rl1, Itga2b, Cited2, Fam110c, Creb3l1, Rgs13, Tpsab1, Cyp26a1, Serpinb1a, Slc18a2, Gmpr, Rprm, Ero1l, Il4, Cd200r3, Glul, Kit, Lat, Alox5, Gchfr, mt-Atp6, Lat2, Prss34, Poln, Klk8, 4932438H23Rik, Slc6a13, Avil, Socs2, Smco4, Ier3, Lxn, Gpr171, Adk and Gata1, wherein T cell Topic 5 comprises one or more genes or polypeptides selected from the group consisting of 1700061F12Rik, Il13, Scin, Lgmn, Hlf, Smco4, Npnt, Il17rb, Deptor, Gata3, Gm2a, Il6, Il17a, Ltb4r1, Fgl2, Areg, Fbxl21, AA467197, Il1rl1, Me1, Gm5544, Tmem159, Rasgrp4, 1700012B07Rik, 1700113H08Rik, St6galnac5, Il4, Chdh, Slco2b1, Ccr9, Epas1, Grp, Lztfl1, Gm10369, Kif19a, Tenm4, Serpinf1, Gnb2, Ubox5, Plcl1, Rab31, Ffar2, Slx1b, Asb2, Zfp85, Tmsb4x, Hdc, Pxdc1, Heatr1 and Lgals7, wherein stromal cell Topic 4 comprises one or more genes or polypeptides selected from the group consisting of Ccl21a, Cxcl13, Clu, Ccl19, Acta2, Mfge8, Apoe, Tagln, Cxcl1, Cilp, Ccl2, Il33, Cxcl12, Actg2, Serpina3n, Ccl7, Bst1, Serpina1a, Fmod, Grem1, Serpina1b, Slc36a2, Cnn1, Myh11, Art2b, Actc1, AI838599, Serpina1c, Cr2, Gxylt2, Crym, Dclk1, Serpina1d, Myl9, Parm1, Gm16685, Postn, Chrdl1, Colq, Csn2, Prss12, H2-M2, Trf, Sostdc1, Dsc3, Ctgf, Thbs4, Pcdh15, Rtn4r and A230065H16Rik. In certain embodiments, the one or more biological programs are suppressed, whereby an ILC2 inflammatory response is decreased. In certain embodiments, the one or more agents modulate the expression, activity or function of one or more genes or polypeptides in ILC Topic 2, myeloid cell Topic 1, T cell Topic 5 or stromal cell Topic 4. In certain embodiments, the population of cells is present in the gut of a subject in need thereof. In certain embodiments, the population of cells is an in vitro population of cells. In certain embodiments, the population of cells is an intestinal organoid.

In certain embodiments, the one or more agents comprise an antibody, small molecule, small molecule degrader, genetic modifying agent, antibody-like protein scaffold, aptamer, protein, or any combination thereof. In certain embodiments, the genetic modifying agent comprises a CRISPR system, RNAi system, a zinc finger nuclease system, a TALE, or a meganuclease. In certain embodiments, the CRISPR system is a Class I or Class II CRISPR system. In certain embodiments, the Class II system comprises a Class 2, Type II Cas polypeptide. In certain embodiments, the Type II Cas is a Cas9. In certain embodiments, the Class II system comprises a Class 2, Type V Cas polypeptide. In certain embodiments, the Type V Cas is Cas12a or Cas12b. In certain embodiments, the Class II system comprises a Class 2, Type VI Cas polypeptide. In certain embodiments, the Type VI Cas is Cas13a, Cas13b, Cas13c or Cas13d. In certain embodiments, the CRISPR system comprises a dCas fused or otherwise linked to a nucleotide deaminase. In certain embodiments, the nucleotide deaminase is a cytidine deaminase or an adenosine deaminase. In certain embodiments, the dCas is a dCas9, dCas12, or dCas13.

In another aspect, the present invention provides for a method of quantitating a type 2 immune response comprising determining the ILC2 frequency, wherein increased frequency of ILC2s as compared to a control frequency is associated with an increased type 2 immune response. In certain embodiments, the method further comprises determining the frequency of one or more cells selected from the group consisting of mast cells, macrophages, neutrophils, and CD11b+CD103+ dendritic cells, wherein increased frequency of mast cells, macrophages and/or neutrophils, and/or decreased frequency of CD11b+CD103+ dendritic cells as compared to a control frequency is associated with an increased type 2 immune response.

In another aspect, the present invention provides for a method of quantitating a type 2 immune response comprising determining the expression of one or more genes selected from Table 3 or determining the frequency of the cell types expressing the one or more genes selected from Table 3, wherein changes in expression or frequency according to Table 3 is associated with an increased type 2 immune response. In certain embodiments, the method comprises determining the expression of: one or more genes in ILC2s selected from the group consisting of: Hes1, Il13, Lif, Areg and Il4; one or more genes in mast cells selected from the group consisting of: Mcpt4, Tph1, Mcpt1, Cma1, and Furin; one or more genes in macrophages selected from the group consisting of: Irf7, Isg15, Irf8, Irf1, Ccl7, Ccl2, Cxcl12, Pf4 and Ccl24; and/or one or more genes in plasma cells selected from the group consisting of: Ifi27, Ifitm3, Ifnar1, Ighg1 and Ighe, wherein increased or decreased expression in the cell type according to FIG. 9B or 9C is associated with an increased type 2 immune response.

In another aspect, the present invention provides for a method of quantitating a type 2 immune response comprising determining the frequency of IL-33⁺PDPN⁺ fibroblasts in a subject having an allergy, wherein increased frequency of IL-33⁺PDPN⁺ fibroblasts is associated with an increased type 2 immune response.

In certain embodiments, CGRP is a polypeptide comprising the amino acid sequence of SEQ ID NO: 1. In certain embodiments, the CGRP sequence is modified to increase stability of the polypeptide. In certain embodiments, the intestinal ILCs are KLRG^HiST2⁻ ILCs.

In another aspect, the present invention provides for a method of quantitating a type 2 immune response, comprising detecting a type 2 immune response in a subject in need thereof, wherein when an increased type 2 immune response is detected, the subject is treated according to any embodiment herein.

In certain embodiments, the methods described herein are used to treat IBD. In certain embodiments, IBD comprises a disease selected from the group consisting of ulcerative colitis (UC), Crohn's Disease, collagenous colitis, lymphocytic colitis, ischemic colitis, diversion colitis, Behcet's syndrome, infective colitis, indeterminate colitis, and other disorders characterized by inflammation of the mucosal layer of the large intestine or colon.

In another aspect, the present invention provides for a method of screening for one or more agents capable of modulating an ILC2 immune response comprising administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents; and detecting expression, activity or function of one or more biological programs characterized by ILC Topic 2, myeloid cell Topic 1, T cell Topic 5 or stromal cell Topic 4, wherein ILC Topic 2 comprises one or more genes or polypeptides selected from the group consisting of Calca, Hs3st1, Areg, Il13, Il4, Ccl1, Hes1, Il17rb, Lgals7, Homer2, Il5, Gata3, Deptor, Ptpn13, Ly6a, Hba-a1, Kcnn4, Ccr4, Rxrg, Sub1, 1700061F12Rik, Cntnap2, AA467197, Ptgir, Il10, Nfkb1, Lmo4, Pparg, Plaur, Il9r, Serpine1, Scel, Bmp7, Neb, Sox8, Lpcat2, Samsn1, Alox5, Gpr65, Abhd17c, Gm20186, Gm973, Epas1, Ccr8, D430036J16Rik, Cd6, Stxbp6, 9230102O04Rik, Furin and Klf5, wherein myeloid cell Topic 1 comprises one or more genes or polypeptides selected from the group consisting of Cpa3, Cma1, Mcpt4, Tpsb2, Fcer1a, Hs3st1, Gata2, Cited4, Cyp11a1, Tph1, Furin, Rab27b, Slc45a3, Ccl1, Il13, Il1rl1, Itga2b, Cited2, Fam110c, Creb3l1, Rgs13, Tpsab1, Cyp26a1, Serpinb1a, Slc18a2, Gmpr, Rprm, Ero1l, Il4, Cd200r3, Glul, Kit, Lat, Alox5, Gchfr, mt-Atp6, Lat2, Prss34, Poln, Klk8, 4932438H23Rik, Slc6a13, Avil, Socs2, Smco4, Ier3, Lxn, Gpr171, Adk and Gata1, wherein T cell Topic 5 comprises one or more genes or polypeptides selected from the group consisting of: 1700061F12Rik, Il13, Scin, Lgmn, Hlf, Smco4, Npnt, Il17rb, Deptor, Gata3, Gm2a, Il6, Il17a, Ltb4r1, Fgl2, Areg, Fbxl21, AA467197, 1r11, Me1, Gm5544, Tmem159, Rasgrp4, 1700012B07Rik, 1700113H08Rik, St6galnac5, Il4, Chdh, Slco2b1, Ccr9, Epas1, Grp, Lztfl1, Gm10369, Kif19a, Tenm4, Serpinf1, Gnb2, Ubox5, Plcl1, Rab31, Ffar2, Slx1b, Asb2, Zfp85, Tmsb4x, Hdc, Pxdc1, Heatr1 and Lgals7, wherein stromal cell Topic 4 comprises one or more genes or polypeptides selected from the group consisting of Ccl21a, Cxcl13, Clu, Ccl19, Acta2, Mfge8, Apoe, Tagln, Cxcl1, Cilp, Ccl2, Il33, Cxcl12, Actg2, Serpina3n, Ccl7, Bst1, Serpina1a, Fmod, Grem1, Serpina1b, Slc36a2, Cnn1, Myh11, Art2b, Actc1, AI838599, Serpina1c, Cr2, Gxylt2, Crym, Dclk1, Serpina1d, Myl9, Parm1, Gm16685, Postn, Chrdl1, Colq, Csn2, Prss12, H2-M2, Trf, Sostdc1, Dsc3, Ctgf, Thbs4, Pcdh15, Rtn4r and A230065H16Rik.

These and other aspects, objects, features, and advantages of the example embodiments will become apparent to those having ordinary skill in the art upon consideration of the following detailed description of illustrated example embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

An understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention may be utilized, and the accompanying drawings of which:

FIG. 1—A single-cell expression atlas of intestinal immune cells. (A) Overview. The lamina propria (LP) and Peyer's patch (PP) regions of the small intestine were harvested from mice in homeostasis (“healthy”) or after induction of a type 2 inflammatory reaction to ovalbumin (OVA) (“inflamed”) (left). After enzymatic tissue dissociation, immune cells were captured by fluorescence-activated cell sorting (FACS) (middle) and analyzed by droplet-based 3′scRNA-seq (right). (B) Cell subsets in the intestinal immune cell atlas. scvis learned two-dimensional (2D) representation of 58,067 cell profiles (dots) from both PP and LP regions, shaded and numbered by cluster membership. Clustered are rank ordered by size (from the largest of 7194, cluster 1, to the smallest of 17, cluster 46). DZ, dark zone; LZ, light zone; DN, double negative; C1, cluster 1; C2, cluster 2. (C) Differentially expressed genes. For representative differentially expressed genes (rows) across clusters (columns), shown is the fraction of cells in the cluster that express a gene (dot size) and the z-score of the mean expression of that gene in the cluster (shading; z-score of average log²(TPM+1)). (D) Tissue distribution of non-T and non-B immune cells in homeostasis. Proportion (y axis) of each cell type in LP (triangle) and PP (black circle) regions. Points: independent experiments; Box and-whisker plots show the median, quartiles, and range. *p<4.8×10⁻³, **p<3.8×10⁻⁶, ***p<4.3×10⁻⁷, Wald test. (E) LTi cells are enriched in PP regions. Shown is flow cytometry analysis gated on CD45⁺Lin⁻ CD90.2⁺IL7R⁺RORγt⁺ cells. Left: Numbers adjacent to outlined areas indicate percent ILC3 (left) or LTi cells (right). Right: Summary of results. n=3 mice, mean and SEM; ***p<0.001, Fisher's exact test.

FIG. 2—Increased ILC2 proportions and changes in ILC2 programs are key features in OVA-induced type 2 inflammation. (A-D) Increased ILC2 and mast cell frequencies are prominent features in type 2 inflammation. (A) A 2D embedding as in FIG. 1B, where each cell profile (dot) is shaded by whether it was obtained in homeostatic or OVA-induced inflammatory conditions. (B) Distribution of cell type proportions (y axis) for each non-T and non-B cell subset (x axis) in homeostatic (left bar) or inflammatory (right bar) conditions. Points: independent experiments. Box and-whisker plots show the median, quartiles, and range. *p<1.3×10⁻², **p<4.5×10⁻⁴, ***p<6.1×10⁻⁸, Wald test. (C and D) Flow cytometry analysis of frequencies of mast cells (C, gated on CD45⁺Lin⁻) and ILC2s (D, gated on CD45⁺Lin⁻ CD90.2⁺IL7R⁺) in mice treated with PBS (black) or OVA (grey). Left: representative FACS plots; Right: summary of results. Points: individual mice; data are from two independent experiments. mean and SEM; **p<0.01, Student's t test. (E) ILC2s and mast cells show the most prominent changes in expression programs in type 2 inflammation. Number of genes significantly induced (black) or inhibited (grey) (|fold change|≥2, FDR<0.05, expressed at least in 25% of cells at the up-regulation side; shaded bar) by OVA-induced type 2 inflammation in each cell subset (column) from the LP or PP regions (label on left).

FIG. 3—Topic modeling of cell type-specific programs in response to intestinal type 2. inflammation predicts Calca as a top gene in ILC2s (A-E) Inflammation associated programs in specific cell subsets. Shown are some of the topics that have differential scores between steady state (PBS) and inflammatory conditions (OVA) for myeloid cells (A), ILCs (B), T cells (C, D) or stromal cells (E). Left: Bar plot shows the score (x axis) of top ranked genes for this topic (y axis). Top right: a portion of the 2D embedding in FIG. 1B, showing only cells from the noted subset cells, shaded by the topic's weight in the cell (top right). Bottom right: empirical cumulative density function (y axis) of topic weights (x axis) for cells from mice treated with PBS (black curve) or OVA (grey curve). p values: Mann-Whitney U test. (F) Increased number of IL-33⁺PDPN⁺ fibroblasts in inflammation. Left: Representative IF images of small intestines from mice at steady state (PBS) or inflammatory (OVA) conditions. Arrow, IL-33⁺PDPN⁺ fibroblasts; Scale bars, 50 Right: Quantified cell densities. Points: individual mice; data are from two independent experiments. mean and SEM, **p<0.01, Student's t test.

FIG. 4—α-CGRP suppresses IL-25-induced activation and expansion of intestinal KLRG1⁺ ILC2s in vitro. (A) Cells expressing Calca gene. 2D embedding as in FIG. 1B where cells (dots) are colored by relative expression of Calca (log²(TPM+1)). (B) α-CGRP exon specifically induced in inflammation. Expression level (y axis, Quantitative PCR normalized to Gapdh) of α-CGRP exon of Calca gene, Calcrl, and Ramp1 in intestinal KLRG1⁺ ILC2s isolated from control (black) or OVA-treated (grey) mice. Points: individual experiment; mean and SEM, *p<0.01, **p<0.01, Student's t test. (C and D) α-CGRP co-treatment abrogates most of the IL-25 induced response in ILC2s in vitro. (C) Expression (shaded bar, Z score) of genes (rows) significantly induced in ILC2s (Fold change≥2, FDR<0.05) by IL-25 compared to control, across different conditions (columns). (D) Box and whisker (min to max) plot of the average Z scores (y axis) of the IL-25-induced genes in (C). ***false discovery rate [FDR]<0.001, Student's t test. (E) α-CGRP suppresses IL-25-induced proliferation of ILC2s. Left: Distribution of number of cell divisions (y axis, % of maximum observed number) monitored by flow cytometry in KLRG1⁺ILC2s labeled with CellTrace Violet and stimulated with IL-25 or IL-25 plus α-CGRP for 60 hours. Right: Percent of dividing cells (y axis) in each treatment (x axis). Points: individual experiments. mean and SEM, *p<0.05, Student's t test.

FIG. 5—α-CGRP antagonizes expansion of intestinal KLRG1⁺ ILC2s in vivo. (A) Experimental design. Mice were intraperitoneally injected with vehicle, IL-25 or IL-25 and α-CGRP daily for two days. (B) α-CGRP co-treatment antagonizes CD3⁻KLRG1⁺ ILC2 expansion in vivo. Representative IF images of CD3⁻KLRG1⁺ ILC2 (arrows) in small intestines of mice treated as in A. Scale bars, 100 Data are representative of three mice in each condition. (C-E) α-CGRP antagonizes the expansion of ST2⁻KLRG1⁺ ILC2s specifically. (C) Flow cytometry analysis of ILC2s in mLNs cells gated on CD45⁺Lin⁻CD90.2⁺IL7R⁺ from mice treated as in (A). (D) Frequency (y axis) of ST2⁻KLRG1⁺ ILC2s in total CD45⁺ cells in mLNs of mice treated as in A. Points: individual mice. Data from three independent experiments. mean and SEM, *FDR<0.05, ***FDR<0.001, Student's t test. (E) Frequency (y axis) of ST2⁺ ILC2s in total CD45⁺ cells in mLNs of mice treated as in A. Point: individual mice. Data are from three independent experiments. mean and SEM, ns: FDR>0.05, *FDR<0.05, **FDR<0.01, Student's t test. (F and G) α-CGRP treatment antagonizes intestinal ILC2 expansion following OVA intraperitoneal sensitization experiment. (F) Experimental overview. (G) Percent of GATA3⁺ ILC2 (y axis) in total CD45⁺ cells in the small intestine of mice treated as in F. Point: individual mice. Data are from three independent experiments. mean and SEM, *p<0.05, Student's t test.

FIG. 6—α-CGRP is produced by ChAT⁺ enteric neurons in steady state and maintains KLRG1⁺ ILC2 homeostasis in vivo. (A and B) ChAT⁺ enteric neurons express α-CGRP. (A) t-SNE plot of 1105 enteric neuron profiles from Wnt1-Cre:R26Tomato mice (Zeisel et al., 2018), where each neuron (dot) is numbered by cluster assignment. (B) Distribution of expression levels (y axis, log₂(TPM+1)) of Nmu, Calca, Calcb and Calcrl gene in the enteric neurons in each cluster in A (x axis). (C) co-localization of ChAT and CGRP in the small intestines. Representative IF images of the small intestines of wild type mice. Scale bar, 50 Data are representative of three mice. (D) Expression program induced by α-CGRP in ILC2s in vitro. Relative expression (rowwise Z score of log₂(FPKM+1)) of genes (rows) significantly induced or suppressed by α-CGRP stimulation (|Fold change|≥2, FDR<0.05), across conditions (columns). Key genes are highlighted. (E) α-CGRP in ILC2s in vitro reprograms chromatin accessibility especially at loci of a cAMP response module. Left: Chromatin accessibility (log₂(#cuts+1), Methods) of loci (rows) with differential accessibility in ILC2s treated by α-CGRP vs. control in vitro. Right: Statistical significance (x axis, −log₁₀(q-value)) of molecular functions (y axis) whose associated genes are enriched in proximity to these differentially accessible ATAC-Seq peaks. Dashed line: qvalue=0.01. (F and G) Foskolin suppresses ILC2 proliferation but does not impact cell viability. (F) Left: Distribution of number of cell divisions (y axis, % of maximum observed number) monitored by flow cytometry in KLRG1⁺ ILC2s labeled with CellTrace Violet and stimulated with IL-25 and DMSO or forskolin for 40 hours. Right: Percent of divided cells (y axis) in each treatment (x axis). Points: individual experiments. mean and SEM, ***p<0.001, Student's t test. (G) Left: Cell viability monitored by flow cytometry in cells in F stained with 7AAD. Right: Percent of live (7AAD⁻) cells (y axis) in each treatment (x axis). Points: individual experiments. mean and SEM, NS: p>0.05, Student's t test. (H) Adenylate cyclase inhibitor (SQ22, 536) treatment partially rescues α-CGRP inhibition of ILC2 proliferation. Percent of divided cells (y axis) assayed as in F, in ILC2s treated in vivo with IL-25 and DMSO alone (black) or with α-CGRP (grey) or α-CGRP+Forskolin (dark grey). Points: individual experiments. mean and SEM, **p<0.01,*** p<0.001, Student's t test. (I and J) α-CGRP KO affects ILC2 expansion in vivo. (I) Left: Flow cytometry analysis of intestinal KLRG1⁺ cells among cells gated on CD45⁺Lin⁻ CD90.2⁺IL7R⁺ in α-CGRP WT and KO mice in homeostasis. Right: Percentage of KLRG1⁺ILC2s (y axis) in α-CGRP WT and KO mice. Points: individual mice. Data from three independent experiments. mean and SEM, **p<0.01, Student's t test. (J) Left: Representative IF images of tuft cells (arrows) in the small intestine of α-CGRP WT or KO mice. Scale bars, 50 Right: Density of tuft cells (y axis, number per mm²) in WT and KO. Points: individual mice. Data are from the independent experiments. mean and SEM, *p<0.05, Student's t test.

FIG. 7—A model of neuronal signals orchestrating ILC2 responses. Intestinal ILC2s sense different neuropeptides, including NMU, epinephrine (EPI) and CGRP from enteric neurons via expressing corresponding GPCRs. The amplifier NMUR1 signals through Gα_q/11and inhibits cAMP level, whereas the negative regulators CRLR and β₂AR are coupled with Gα_sprotein that results in cAMP accumulation. cAMP suppresses expansion of ILC2s but increases IL-5 expression. Thus, selective activation of different subgroups of a subunits of G proteins coupled with variable concentration of cAMP might be utilized by ILC2s to fine-turn the response to neuronal signaling.

FIG. 8—FACS, single-cell expression and IF staining analysis of intestinal immune cells, related to FIG. 1. (A) Experimental overview. (B) Depletion of common cell types by FACS. Shown are representative FACS plots for sorting lgD^lowcells (left) or CD3⁻CD19⁻ cells (right) from PP and LP regions. CD45⁻ cells were not included in LP. (C) An LP and PP cell atlas. A 2D embedding as in FIG. 1B, but showing separately only the 36,797 cells from PP regions (left) or the 21,270 cells from LP (right). (D) Cluster quality measures. Top: Distribution of number of UMIs (y axis, log₁₀-transformed) in both LP and PP cells in each cluster from FIG. 1B (x axis). Bottom: distribution of doublet scores (y axis, Methods) of only PP cells in each cluster from FIG. 1B (x axis). (E) Clusters of specific cell types in the atlas. A 2D embedding as in FIG. 1B, but showing separately only the cells in each cell lineage or group as labeled. (F) Differentially expressed genes between ILC3 and LTi. Fraction of cells in the cluster that express a gene (dot size) and the z-score of the mean expression of that gene in those cells that express it in the cluster (shading; z-score of average log²(TPM+1)). (G) Tissue distribution of B (left) and T (right) cells between LP and PP in homeostasis. Proportion (y axis) of each cell type (x axis) in LP (triangle) and PP (black circle) regions. Points: independent experiments; Box-and-whisker plots show the median, quartiles, and range. *p<6×10⁻⁰⁵, **p<4×10⁻¹⁰, ***p<2.5×10⁻¹⁵³Wald test. (H) Differential distribution of plasma cells and GC B cells. Representative IF image of the small intestines of wild type mice. Dashed line: PP region; Small dashed region: GC area; arrow: CD138⁺ plasma cell; scale bar, 100 μm. Data are representative of three mice.

FIG. 9—Cell proportions in T and B cells, and gene expression in ILC2s, mast cells, macrophages and plasma cells in OVA-induced type 2 inflammation, related to FIG. 2. (A) Distribution of cell type proportions (y axis) in B cells (left) and T cells in homeostatic (black) or inflammatory (grey) conditions. Points: independent experiments. Box-and-whisker plots show the median, quartiles, and range. (B) Differentially expressed genes in ILC2s, mast cells, macrophages and plasma cells. Shown are genes repressed (left of zero) or induced (right of zero) (|fold change|≥2, FDR<0.05, likelihood ratio test, frequency of expressing cells ≥25% at the up-regulation side) by the inflammation in each labeled cell type. Dots: genes, with key ones labeled. (C) Distribution of expression levels (y axis, log²(TPM+1)) of Igh genes (labeled) in plasma cells in homeostatic (left) or inflammatory (right) conditions. *p<2.8×10⁻⁵, **p<2.9×10⁻¹³, ***p<1.5×10⁻¹⁰⁷, likelihood ratio test.

FIG. 10—Topic modeling on T cells, B cells, DCs, ILCs, myeloid cells and stromal cells, and co-expression of CCL21 and IL-33 in PDPN⁺ stromal cells in the small intestine, related to FIG. 3. (A-F) Biological programs in each cell subset revealed by topic modeling. Shown are topics in T cells (A), B cells (B), ILCs (C), myeloid cells (D), DCs (E) and stromal cells (F). Top (A-D) and left (E and F): a portion of the 2D embedding in FIG. 1B, showing only cells from the noted subset cells, shaded by the topic's weight in the cell. Bottom (A-D) and right (E and F): empirical cumulative density function (y axis) of topic weights (x axis) for cells from mice treated with PBS (black curve) or OVA (grey curve). p values: Mann-Whitney U test. (G) co-localization of CCL21 and IL-33 in subsets of PDPN⁺ stromal cells (arrow) in the small intestines. Representative IF images of the small intestines of wild type mice. Scale bars, 50 μm. Data are representative of three mice.

FIG. 11—Expression of Calca, Calcrl, Ramp1 and Il5 genes in intestinal KLRG1⁺ ILC2s in homeostatic and inflammatory conditions, related to FIG. 4. (A) Distribution of expression levels (y axis, log₂(TPM+1)) of Calca (top), Calcrl (middle), Ramp1 (bottom) in each cell types (x axis) in mice treated with PBS (black) or OVA (grey). ILC2s are highlighted. *P<0.05, **P<2.3×10⁻⁰⁶, likelihood ratio test. (B) Expression level (y axis, Quantitative PCR normalized to Gapdh) of CT exon of Calca gene in intestinal KLRG1⁺ ILC2s isolated from PBS or OVA-treated mice. Points: individual experiment; mean and SEM, NS: p>0.05, Student's t test. (C) α-CGRP promotes Il5 expression in intestinal ILC2s. Shown are Z scores of Il5 gene in FIG. 4C. Points: individual sample; mean and SEM, *FDR<0.05, **FDR<0.01, ***FDR<0.001, Student's t test.

FIG. 12—α-CGRP suppress expansion of intestinal KLRG1⁺ ILC2s in two in vivo models, related to FIG. 5. (A) α-CGRP co-treatment antagonizes CD3⁻KLRG1⁺ ILC2 expansion in vivo. Representative IF images of CD3⁻KLRG1⁺ ILC2 (arrows) in small intestines of mice treated as in FIG. 5A. Scale bars, 200 Data are representative of three mice in each condition. (B) α-CGRP suppresses the expansion of ST2⁻KLRG1⁺ ILC2s in mLNs. Quantification of frequency (y axis) of ST2⁻KLRG1⁺ ILC2s in FIG. 5C. Points: individual mice. Data from three independent experiments. mean and SEM, *FDR<0.05, ***FDR<0.001, Student's t test. (C, D) α-CGRP treatment antagonizes intestinal ILC2 expansion in OVA-induced inflammation model. (C) Flow cytometry analysis of ILC2s (gated on CD45⁺Lin⁻ CD90.2⁺IL7R⁺) in the small intestines in mice treated as in FIG. 5F. (D) Percent of GATA3⁺ ILC2 (y axis) in all ILCs in the small intestine of mice in (C). Points: individual mice. Data from three independent experiments. mean and SEM, **p<0.01, Student's t test.

FIG. 13—scRNA-seq analysis of intestinal epithelium and enteric neurons, and ATAC-seq analysis of intestinal ILC2s, related to FIG. 6. (A) Undetectable expression of Calca and Calcrl in epithelium of wild type mice (Haber et al, 2017). Distribution of expression levels (y axis, log₂(TPM+1)) of Calca (top), Ramp1 (middle), Calcrl (bottom) in each epithelial cell type as labeled. (B) Marker genes of each enteric neuron clusters. Heatmap showing relative expression (Z score of log₂(TPM+1)) of top 5 marker genes (row) of each cluster (column) in FIG. 6A. (C) Distribution of expression levels (y axis, log₂(TPM+1)) of Chat, Gal, Il13ra1, Il4ra and Tslp gene in each cluster (x axis) in FIG. 6A. (D) Interaction between ChAT-expressing neuron fibers and CD3⁻KLRG1⁺ ILC2s (arrow) in the small intestines. Representative IF images of the small intestines of wild type mice. Scale bar, 25 Data are representative of three mice.

The figures herein are for illustrative purposes only and are not necessarily drawn to scale.

DETAILED DESCRIPTION OF THE EXAMPLE EMBODIMENTS
General Definitions

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Definitions of common terms and techniques in molecular biology may be found in Molecular Cloning: A Laboratory Manual, 2nd edition (1989) (Sambrook, Fritsch, and Maniatis); Molecular Cloning: A Laboratory Manual, 4th edition (2012) (Green and Sambrook); Current Protocols in Molecular Biology (1987) (F. M. Ausubel et al. eds.); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (1995) (M. J. MacPherson, B. D. Hames, and G. R. Taylor eds.): Antibodies, A Laboratory Manual (1988) (Harlow and Lane, eds.): Antibodies A Laboraotry Manual, 2^ndedition 2013 (E. A. Greenfield ed.); Animal Cell Culture (1987) (R. I. Freshney, ed.); Benjamin Lewin, Genes IX, published by Jones and Bartlet, 2008 (ISBN 0763752223); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0632021829); Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 9780471185710); Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992); and Marten H. Hofker and Jan van Deursen, Transgenic Mouse Methods and Protocols, 2^ndedition (2011).

As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.

The term “optional” or “optionally” means that the subsequent described event, circumstance or substituent may or may not occur and that the description includes instances where the event or circumstance occurs and instances where it does not.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.

The terms “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of +/−10% or less, +/−5% or less, +/−1% or less, and +/−0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed.

As used herein, a “biological sample” may contain whole cells and/or live cells and/or cell debris. The biological sample may contain (or be derived from) a “bodily fluid”. The present invention encompasses embodiments wherein the bodily fluid is selected from amniotic fluid, aqueous humour, vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen (earwax), chyle, chyme, endolymph, perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus (including nasal drainage and phlegm), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum (skin oil), semen, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, vomit and mixtures of one or more thereof. Biological samples include cell cultures, bodily fluids, cell cultures from bodily fluids. Bodily fluids may be obtained from a mammal organism, for example by puncture, or other collecting or sampling procedures.

The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed.

Various embodiments are described hereinafter. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader aspects discussed herein. One aspect described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced with any other embodiment(s). Reference throughout this specification to “one embodiment”, “an embodiment,” “an example embodiment,” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” or “an example embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention. For example, in the appended claims, any of the claimed embodiments can be used in any combination.

Reference is made to International Application Nos. PCT/US2018/024082, published as WO 2018/175924A1 on Sep. 27, 2018, and PCT/US2019/030911, published as WO2019/213660A2 on Nov. 7, 2019. Reference is also made to Xu et al., Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses. Immunity. 2019 Oct. 15; 51(4):696-708.e9.

All publications, published patent documents, and patent applications cited herein are hereby incorporated by reference to the same extent as though each individual publication, published patent document, or patent application was specifically and individually indicated as being incorporated by reference.

Overview

Embodiments disclosed herein provide methods and compositions for modulating an innate immune response, in particular an innate lymphoid cell class 2 innate immune response by modulating activity of CGRP signaling. Embodiments disclosed herein also provide for methods of monitoring an innate lymphoid cell class 2 innate immune response in response to disease or treatment.

It is an objective of the present invention to identify molecular cues that modulate ILC2 responses to alarmins (e.g., for therapeutic applications). It is an objective of the present invention to modulate ILC2 immune responses and cell states using CGRP either alone or in combination with other treatments. It is another objective to modulate ILC2 immune responses using CGRP in combination with agents currently in use for the modulation of immune responses or associated with regulation of immune responses.

Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation, involving interaction of multiple immune cell types. Here, Applicants combine scRNA-seq with physiological and genetic perturbations to dissect the cellular circuit of type 2 intestinal inflammation. To systematically characterize this response, Applicants analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA-seq (scRNA-seq) at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA). Specifically, to uncover key responding cellular components, Applicants profiled individual immune cells in the lamina propria (LP) and Peyer's patches (PPs), regions of the small intestine enriched for immune cells, in homeostasis and in an intestinal type 2 inflammatory model. Analysis revealed broad shifts in both cell type composition and cell programs in response to the inflammation, especially in ILC2s. Among the key transcripts associated with an inflammation-induced program in intestinal KLRG1⁺ ILC2s was exon 5 of Calca, which encodes the alpha-calcitonin gene-related peptide (α-CGRP). Specifically, computational analysis showed that both cell compositions and cell programs shifted in response to inflammation, in particular the prominent induction of α-CGRP transcription in ILC2s. α-CGRP antagonized IL-25-induced activation of intestinal KLRG1⁺ILC2s and reduced ILC2 frequency in an OVA reaction model. In inflammatory conditions, α-CGRP suppressed activation of ILC2s, but induced IL-5 expression. In vivo stimulation with α-CGRP alone induced the expression of a cyclic AMP (cAMP) response gene module and suppressed cell proliferation. In homeostasis in vivo, α-CGRP was predominantly expressed by two subsets of ChAT⁺ enteric neurons, and genetic perturbation of α-CGRP increased the proportion of intestinal KLRG1⁺ ILC2s and the number of Tuft cells. Embodiments disclosed herein provide methods for targeting α-CGRP-mediated neuronal signaling for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery.

The discovery presented herein highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces. Moreover, Applicants have discovered novel regulatory mechanisms for modulating the balance between tissue protective ILCs and tissue inflammatory cells. In certain embodiments, the methods and compositions described herein may be used to shift the balance of ILC2 responses in order to treat inflammatory allergic diseases and cancer.

Expression Signatures

In certain example embodiments, the therapeutic, diagnostic, and screening methods disclosed herein target, detect, or otherwise make use of one or more biomarkers of an expression signature. As used herein, the term “biomarker” can refer to a gene, an mRNA, cDNA, an antisense transcript, a miRNA, a polypeptide, a protein, a protein fragment, or any other nucleic acid sequence or polypeptide sequence that indicates either gene expression levels or protein production levels. Accordingly, it should be understood that reference to a “signature” in the context of those embodiments may encompass any biomarker or biomarkers whose expression profile or whose occurrence is associated with a specific cell type, subtype, or cell state of a specific cell type or subtype within a population of cells (e.g., inflammatory or homeostatic ILC2 cells) or a specific biological program. As used herein the term “module” or “biological program” can be used interchangeably with “expression program” and refers to a set of biomarkers that share a role in a biological function (e.g., an activation program, cell differentiation program, proliferation program). Biological programs can include a pattern of biomarker expression that result in a corresponding physiological event or phenotypic trait. Biological programs can include up to several hundred biomarkers that are expressed in a spatially and temporally controlled fashion. Expression of individual biomarkers can be shared between biological programs. Expression of individual biomarkers can be shared among different single cell types; however, expression of a biological program may be cell type specific or temporally specific (e.g., the biological program is expressed in a cell type at a specific time). Expression of a biological program may be regulated by a master switch, such as a nuclear receptor or transcription factor. As used herein, the term “topic” refers to a biological program as determined by topic modeling. Topics are described further herein. The biological program (topic) can be modeled as a distribution over expressed biomarkers.

In certain embodiments, the expression of the signatures disclosed herein (e.g., inflammatory, homeostatic or CGRP signature) is dependent on epigenetic modification of the biomarkers or regulatory elements associated with the signatures (e.g., chromatin modifications or chromatin accessibility). Thus, in certain embodiments, use of signature biomarkers includes epigenetic modifications of the biomarkers that may be detected or modulated. As used herein, the terms “signature”, “expression profile”, or “expression program” may be used interchangeably (e.g., expression of genes, expression of gene products or polypeptides). It is to be understood that also when referring to proteins (e.g. differentially expressed proteins), such may fall within the definition of “gene” signature. Levels of expression or activity may be compared between different cells in order to characterize or identify, for instance, signatures specific for cell (sub)populations. Increased or decreased expression or activity or prevalence of signature biomarkers may be compared between different cells in order to characterize or identify for instance specific cell (sub)populations. The detection of a signature in single cells may be used to identify and quantitate for instance specific cell (sub)populations. A signature may include a biomarker whose expression or occurrence is specific to a cell (sub)population, such that expression or occurrence is exclusive to the cell (sub)population. An expression signature as used herein, may thus refer to any set of up- and/or down-regulated biomarkers that are representative of a cell type or subtype. An expression signature as used herein, may also refer to any set of up- and/or down-regulated biomarkers between different cells or cell (sub)populations derived from a gene-expression profile. For example, an expression signature may comprise a list of biomarkers differentially expressed in a distinction of interest.

The signature according to certain embodiments of the present invention may comprise or consist of one or more biomarkers, such as for instance 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of two or more biomarkers, such as for instance 2, 3, 4, 5, 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of three or more biomarkers, such as for instance 3, 4, 5, 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of four or more biomarkers, such as for instance 4, 5, 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of five or more biomarkers, such as for instance 5, 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of six or more biomarkers for instance 6, 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of seven or more biomarkers, such as for instance 7, 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of eight or more biomarkers, such as for instance 8, 9, 10 or more. In certain embodiments, the signature may comprise or consist of nine or more biomarkers, such as for instance 9, 10 or more. In certain embodiments, the signature may comprise or consist of ten or more biomarkers, such as for instance 10, 11, 12, 13, 14, 15, or more. It is to be understood that a signature according to the invention may for instance also include different types of biomarkers combined (e.g. genes and proteins).

In certain embodiments, a signature is characterized as being specific for a particular cell or cell (sub)population if it is upregulated or only present, detected or detectable in that particular cell or cell (sub)population, or alternatively is downregulated or only absent, or undetectable in that particular cell or cell (sub)population. In this context, a signature consists of one or more differentially expressed genes/proteins or differential epigenetic elements when comparing different cells or cell (sub)populations, including comparing different immune cells or immune cell (sub)populations (e.g., ILC2 cells), as well as comparing immune cells or immune cell (sub)populations with other immune cells or immune cell (sub)populations. It is to be understood that “differentially expressed” biomarkers include biomarkers which are up- or down-regulated as well as biomarkers which are turned on or off. When referring to up- or down-regulation, in certain embodiments, such up- or down-regulation is preferably at least two-fold, such as two-fold, three-fold, four-fold, five-fold, or more, such as for instance at least ten-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, or more. Alternatively, or in addition, differential expression may be determined based on common statistical tests, as is known in the art. Differential expression of biomarkers may also be determined by comparing expression of biomarkers in a population of cells or in a single cell. In certain embodiments, expression of one or more biomarkers is mutually exclusive in cells having a different cell state or subtype (e.g., two genes are not expressed at the same time). In certain embodiments, a specific signature may have one or more biomarkers upregulated or downregulated as compared to other biomarkers in the signature within a single cell (see, e.g., FIG. 6D). Thus a cell type or subtype can be determined by determining the pattern of expression in a single cell.

As discussed herein, differentially expressed biomarkers may be differentially expressed on a single cell level, or may be differentially expressed on a cell population level. Preferably, the differentially expressed biomarkers as discussed herein, such as constituting the expression signatures as discussed herein, when as to the cell population level, refer to biomarkers that are differentially expressed in all or substantially all cells of the population (such as at least 80%, preferably at least 90%, such as at least 95% of the individual cells). This allows one to define a particular subpopulation of cells. As referred to herein, a “subpopulation” of cells preferably refers to a particular subset of cells of a particular cell type (e.g., ILC2) which can be distinguished or are uniquely identifiable and set apart from other cells of this cell type. The cell subpopulation may be phenotypically characterized, and is preferably characterized by the signature as discussed herein. A cell (sub)population as referred to herein may constitute of a (sub)population of cells of a particular cell type characterized by a specific cell state.

When referring to induction, or alternatively suppression of a particular signature, preferable is meant induction or alternatively suppression (or upregulation or downregulation) of at least one biomarker of the signature, such as for instance at least two, at least three, at least four, at least five, at least six, or all biomarkers of the signature.

Example gene signatures and topics are further described below.

IL-25 Inflammatory ILC2 Gene Signature

In certain embodiments, an IL-25 inflammatory ILC2 gene signature (e.g., IL-25 induced genes; or signature of differentially expressed genes between ILC2s treated with IL-25 and IL-25+CGRP; or IL-25 induced genes that can be modulated by CGRP) comprises one or more biomarkers selected from Table A.

TABLE A

I15
Furin
Gem

Nr4a1
Ptgs2
Il9

Irf4
Nfkbiz
Tph1

Ccr4
Thbd
Gadd45g

Egr2
Ntn1
Prelp

Il6
Flt4
Pecam1

Myc
Fxyd6
Pcl13

Timp3
Csf2
Reln

Pim2
Gpr97
Aqp1

Cntf
Mmrn1
Ptger2

Mras
Prss23
Emcn

Cldn5
Adam8
Lyve1

Il13
Sdpr
Gstm1

Lcn2
Gm1987

In one example embodiment, the IL-25 inflammatory ICL2 signature consists of the biomarkers Il5, Furin, Gem, Nr4a1, Ptgs2, Il9, Irf4, Nfkbiz, Tph1, Ccr4, Thbd, Gadd45g, Egr2, Ntn1, Prelp, Il6, Flt4, Pecam1, Myc, Fxyd6, Bcl3, Timp3, Csf2, Reln, Pim2, Gpr97, Aqp1, Cntf, Mmrn1, Ptger2, Mras, Prss23, Emcn, Cldn5, Adam8, Lyve1, Il13, Sdpr, Gstm1, Lcn2 and Gm1987 (see, FIG. 4C). In certain embodiments, IL-25 induces an inflammatory gene signature and this signature can be modulated (e.g., reversed or partially reversed) by treatment with CGRP.

In one example embodiment the IL-25 Inflammatory ILC2 signature comprises Il5 and at least N additional biomarker from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Furin and at least one of N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Gem and at least one of N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Nr4a1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Ptgs2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises 119 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Irf4 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Nfkbiz and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Tph1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Ccr4 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Thbd and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Gadd45g and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Egr2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Ntn1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Prelp and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Il6 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Flt4 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Pecam1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Myc and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Fxyd6 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Pcl13 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Timp3 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Csf2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Reln and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Pim2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Gpr97 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Aqp1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Cntf and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Mmrn1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Ptger2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Mras and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Prss23 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Emcn and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Cldn5 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Adam8 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Lyve1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Il13 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Sdpr and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Gstm1 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Lcn2 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

In another example embodiment the IL-25 Inflammatory ILC2 signature comprises Gm1987 and at least N additional biomarkers from Table A, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 51.

ILC2 Signature (Topic 2)

In certain embodiments, an ILC2 expression signature (Topic 2) comprises one or more biomarkers selected from Table B.

TABLE B

Calca
Hs3st1
Areg

Il13
Il4
Ccl1

Hes1
Il17rb
Lgals7

Homer2
Il5
Gata3

Deptor
Ptpn13
Ly6a

Hba-a1
Kcnn4
Ccr4

Rxrg
Sub1
1700061F12Rik

Cntnap2
AA467197
Ptgir

Il10
Nfkb1
Lmo4

Pparg
Plaur
Il9r

Serpine1
Scel
Bmp7

Neb
Sox8
Lpcat2

Samsn1
Alox5
Gpr65

Abhd17c
Gm20186
Gm973

Epas1
Ccr8
D430036J16Rik

Cd6
Stxbp6
9230102O04Rik

Furin
Klf5.

In one example embodiment, the ILC2 signature consists of Calca, Hs3st1, Areg, Il13, Il4, Ccl1, Hes1, Il17rb, Lgals7, Homer2, Il5, Gata3, Deptor, Ptpn13, Ly6a, Hba-a1, Kcnn4, Ccr4, Rxrg, Sub1, 1700061F12Rik, Cntnap2, AA467197, Ptgir, Il10, Nfkb1, Lmo4, Pparg, Plaur, Il9r, Serpine1, Scel, Bmp7, Neb, Sox8, Lpcat2, Samsn1, Alox5, Gpr65, Abhd17c, Gm20186, Gm973, Epas1, Ccr8, D430036J16Rik, Cd6, Stxbp6, 9230102O04Rik.

In another example embodiment, the ILC2 signature comprises one gene from Table B and at least N additional biomarkers selected from Table B (e.g., Calca and one or more additional genes from Table B), wherein N is equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

Myeloid Cell Signature (Topic 1)

In certain embodiments, myeloid cell signature (Topic 1) comprises one or more genes or polypeptides selected from the group consisting of: Cpa3, Cma1, Mcpt4, Tpsb2, Fcer1a, Hs3st1, Gata2, Cited4, Cyp11a1, Tph1, Furin, Rab27b, Slc45a3, Ccl1, Il13, Il1rl1, Itga2b, Cited2, Fam110c, Creb3l1, Rgs13, Tpsab1, Cyp26a1, Serpinb1a, Slc18a2, Gmpr, Rprm, Ero1l, Il4, Cd200r3, Glul, Kit, Lat, Alox5, Gchfr, mt-Atp6, Lat2, Prss34 Poln, Klk8, 4932438H23Rik, Slc6a13, Avil, Socs2, Smco4, Ier3, Lxn, Gpr171, Adk and Gata1.

In another example embodiment, the myeloid cell signature comprises one gene from topic 1 and at least N additional biomarkers selected from topic 1 (e.g., Cpa3 and one or more additional genes), wherein N is equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

T Cell Signature (Topic 5)

In one example embodiment, T cell signature (Topic 5) comprises one or more genes or polypeptides selected from the group consisting of: 1700061F12Rik, Il13, Scin, Lgmn, Hlf, Smco4, Npnt, Il17rb, Deptor, Gata3, Gm2a, Il6, Il17a, Ltb4r1, Fgl2, Areg, Fbxl21, AA467197, Il1rl1, Me1, Gm5544, Tmem159, Rasgrp4, 1700012B07Rik, 1700113H08Rik, St6galnac5, Il4, Chdh, Slco2b1, Ccr9, Epas1, Grp, Lztfl1, Gm10369, Kif19a, Tenm4, Serpinf1, Gnb2, Ubox5, Plcl1, Rab31, Ffar2, Slx1b, Asb2, Zfp85, Tmsb4x, Hdc, Pxdc1, Heatr1 and Lgals7.

In another example embodiment, the T cell signature comprises one gene from topic 5 and at least N additional biomarkers selected from topic 5 (e.g., 1700061F12Rik and one or more additional genes), wherein N is equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

Stromal Cell Signature (Topic 4)

In one example embodiment, a stromal cell signature (Topic 4) comprises one or more genes or polypeptides selected from the group consisting of: Ccl21a, Cxcl13, Clu, Ccl19, Acta2, Mfge8, Apoe, Tagln, Cxcl1, Cilp, Ccl2, Il33, Cxcl12, Actg2, Serpina3n, Ccl7, Bst1, Serpina1a, Fmod, Grem1, Serpina1b, Slc36a2, Cnn1, Myh11, Art2b, Actc1, AI838599, Serpina1c, Cr2, Gxylt2, Crym, Dclk1, Serpina1d, Myl9, Parm1, Gm16685, Postn, Chrdl1, Colq, Csn2, Prss12, H2-M2, Trf, Sostdc1, Dsc3, Ctgf, Thbs4, Pcdh15, Rtn4r and A230065H16Rik.

In another example embodiment, the stromal cell signature comprises one gene from topic 4 and at least N additional biomarkers selected from topic 4 (e.g., Ccl21a and one or more additional genes), wherein N is equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

CGRP Signature

In certain embodiments, treatment of ILC2s with CGRP alone provides for a CGRP gene signature comprising one or more genes selected from the group consisting of: Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5 (see, FIG. 6D showing all genes differentially expressed upon CGRP treatment). In certain embodiments, this signature can be used to monitor an immune response or monitor a response to a treatment (e.g., CGRP). In certain embodiments, a shift to higher expression of the signature indicates that the treatment is reducing an inflammatory response or maintaining homeostasis.

In another example embodiment the CGRP signature comprises Gpr65 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Pdcd1 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Crem and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Egln3 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Adora2a and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Rgs2 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Gna15 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Adrb2 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Gadd45a and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Areg and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Hif1a and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Dusp1 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Pde4b and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Cdkn1a and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Akap12 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

In another example embodiment the CGRP signature comprises Il5 and at least N additional biomarkers from FIG. 6D, wherein N equals 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or up to 150 genes shown in FIG. 6D.

Methods of Maintaining or Inducing Homeostasis of Intestinal ILC2 Cells

The following section provides multiple example embodiments for maintaining or inducing homeostasis of intestinal ILC2 cells. The methods may be administered to subjects at risk for having aberrant activation and or expansion of intestinal ILC2 cells. Thus, the embodiments may be used to prevent and/or treat diseases and disorders characterized by aberrant activation or expansion of intestinal ILC 2 cells.

Modulations of CGRP

In one aspect, methods of maintaining or inducing homeostasis of intestinal ILC2 cells may comprise administering a CGRP, or functional domain thereof, to a subject in need thereof. In certain example embodiments, a subject in need thereof may be a subject at risk for or having aberrant activation and expansion of intestinal ICL2 cells. Examples of diseases or disorders characterized by aberrant activation and expansion of intestinal ILC2 cells include, but are not limited to allergies (e.g., food allergies). As used herein “maintaining” means that if ILC2s are at homeostasis they are maintained in that current state and do not become inflammatory. As used herein “inducing homeostasis” means increasing the amount of homeostatic ILC2s or switching inflammatory ILC2s to homeostatic ILC2s.

The CGRP protein (also known as: Calcitonin Related Polypeptide Alpha, Calcitonin, Calcitonin Gene-Related Peptide 1, Calcitonin Gene-Related Peptide I, Alpha-Type CGRP, Calcitonin 1, CGRP-I, CALC1, Calcitonin/Calcitonin-Related Polypeptide, Alpha, Katacalcin, CGRP1, CGRP, PCT, CT and KC) (HUGO Gene Nomenclature Committee ID NO. HGNC:10489) may be any α-CGRP or β-CGRP, their functional variants, functional fragments or any mammalian orthologues thereof. In certain example embodiments, CGRP also includes peptides having undergone post-translational modifications, such as peptides having covalent attachment of glycosyl groups, acetyl groups, phosphate groups, lipid groups, and the like.

The human peptide α-CGRP (UniProtKB/Swiss-Prot ref: P06881.3) is encoded by the human gene CALCA (NCBI ref: NG_015960.1, NP_001029125.1) and has the sequence: Ala-Cys-Asp-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser- Lys-Ala-Phe-NH2 (SEQ ID NO: 1). In certain example embodiments, the CGRP to be administered is human α-CGRP. In certain example embodiments, the human α-CGRP to be administered is SEQ ID NO: 1 or a functional variant or fragment thereof.

The human peptide β-CGRP (UniProtKB/Swiss-Protref.: P10092.1) is encoded by the human gene CALCB (NCBI ref: NM_000728.4, NP_000719.1), and has the sequence: Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg-Ser-Gly-Gly-Met-Val-Lys-Ser-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Lys- Ala-Phe-NH2 (SEQ ID NO: 2). In certain example embodiments, the CGRP to be administered is human β-CGRP. In certain example embodiments, the human α-CGRP to be administered is SEQ ID NO: 2 or a functional variant or fragment thereof.

The gene name Areg or AREG may refer to the Amphiregulin gene or polypeptide according to NCBI Reference Sequence accession numbers NM_009704.4 or NM_001657.3. The gene name Calca or CALCA may refer to the Calcitonin/calcitonin-related polypeptide, alpha gene or polypeptide according to NCBI Reference Sequence accession numbers NM_001033954.3, NM_007587.2, NM_001033952.2, NM_001033953.2 or NM_001741.2. The gene name Ramp1 or RAMP1 may refer to the Receptor (calcitonin) activity modifying protein 1 gene or polypeptide according to NCBI Reference Sequence accession numbers NM_016894.3, NM_001168392.1, or NM_005855.3.

By functional variant or fragment of CGRP, it is herein referred to peptides which peptide sequence differ from the amino acid sequence of wild type CGRP, but that generally retains all the biological activity of CGRP. In certain embodiments, functional variants of CGRP are ligands binding to and activating the CGRP receptor. Functional variants may also include modified peptides, fusion proteins (e.g., fused to another protein, polypeptide or the like, such as an immunoglobulin or a fragment thereof), or peptides having non-natural amino acids. Functional variants may have an extended residence time in body fluids. In certain embodiments, a variant of CGRP has at least 80, 85, 90, 95, 99% of the biological activity of CGRP. In certain embodiments, a variant of α-CGRP has at least 80, 85, 90, 95, 99% of the biological activity of α-CGRP. In certain embodiments, a variant of β-CGRP has at least 80, 85, 90, 95, 99% of the biological activity of β-CGRP. Preferably, a functional variant of α-CGRP has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity with α-CGRP. Preferably, a functional variant of β-CGRP has at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity with β-CGRP.

As used herein, the term “functional fragments” refers to a specific peptide that has a biological activity of interest, which peptide sequence is a part of the peptide sequence of the reference peptide, and that can be of any length, provided the biological activity of peptide of reference is retained by said fragment.

Modulation Using a CGRP Receptor Agonist

In another aspect, methods of maintaining or inducing homeostasis of intestinal ILC2 cells may comprise administering a CGRP receptor agonist, or functional domain thereof, to a subject in need thereof. In certain example embodiments, a subject in need thereof may be a subject at risk for or having aberrant activation and expansion of intestinal ICL2 cells.

CGRP receptors have been described as heterodimeric molecules formed of the calcitonin receptor-like receptor (CRLR), linked to RAMP1 (CALCRL). RAMP1 is a transmembrane domain protein of the RAMP family, which further comprises RAMP2 and RAMP3. Several types of receptors are known that can be activated by CGRP: CGRP receptor (formed of CRLR and of RAMP1), AM₂receptor (formed of CRLR and of RAMP3), and AMY₁and AMY₃receptors (formed of the calcitonin receptor and of RAMP1 and RAMP3, respectively). The CGRP receptors can therefore be distinguished from the AM₂, AMY₁and AMY₃receptors by the nature of the transmembrane domain of the RAMP family interacting with CRLR.

As used herein, “CGRP receptor”, refers to a protein receptor comprising the CRLR protein Ref NCBI: NP_005786.1), bound to the protein Receptor Activity Modifying Protein 1 (RAMP1) (Ref NCBI: NP_005846.1). Thus, CGRP receptors do not comprise the CRLR protein bound to RAMP2 or RAMP3.

Modulation of One or More Biomarkers of an ILC2 Expression Signature

In certain embodiments, a method of maintaining or inducing homeostasis of intestinal ILC2 cells comprises administering or more agents capable of modulating expression, activity, or function of one or more biomarkers of the IL-25 inflammatory ILC2 gene signature defined in Table A. In another example embodiment, a method of maintaining or inducing homeostasis of intestinal ILC2 cells comprises administering or more agents capable of modulating expression, activity, or function of one or more biomarkers of the IL-25 inflammatory ILC2 gene signature defined at any one of [0058] to [0098].

Modulation of a CGRP Signature

In certain embodiments, a method of maintaining of inducing homeostasis of intestinal ILC2 cells comprises administering one or more agents capable of modulating expression, activity, or function of one or more biomarkers of the CGRP signature defined at any one of [0109] to [0124].

Modulation of Cell-Type Specific Biological Programs

In another aspect, embodiments disclosed herein provide a method of modulating an ILC2 inflammatory response comprising administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity of one or more signatures as defined in in any one of [0099] to [0107].

In one example embodiment, the method comprises administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity of one or more biological programs characterized by ILC Topic 2, wherein ILC Topic 2 comprises one or more genes or polypeptides selected from the group consisting of: Calca, Hs3st1, Areg, Il13, Il4, Ccl1, Hes1, Il17rb, Lgals7, Homer2, Il5, Gata3, Deptor, Ptpn13, Ly6a, Hba-a1, Kcnn4, Ccr4, Rxrg, Sub1, 1700061F12Rik, Cntnap2, AA467197, Ptgir, Il10, Nfkb1, Lmo4, Pparg, Plaur, Il9r, Serpine1, Scel, Bmp7, Neb, Sox8, Lpcat2, Samsn1, Alox5, Gpr65, Abhd17c, Gm20186, Gm973, Epas1, Ccr8, D430036J16Rik, Cd6, Stxbp6, 9230102O04Rik, Furin and Klf5.

In one example embodiment, the method comprises administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity of one or more biological programs characterized by myeloid cell Topic 1, wherein myeloid cell Topic 1 comprises one or more genes or polypeptides selected from the group consisting of: Cpa3, Cma1, Mcpt4, Tpsb2, Fcer1a, Hs3st1, Gata2, Cited4, Cyp11a1, Tph1, Furin, Rab27b, Slc45a3, Ccl1, Il13, Il1rl1, Itga2b, Cited2, Fam110c, Creb3l1, Rgs13, Tpsab1, Cyp26a1, Serpinb1a, Slc18a2, Gmpr, Rprm, Ero1l, Il4, Cd200r3, Glul, Kit, Lat, Alox5, Gchfr, mt-Atp6, Lat2, Prss34, Poln, Klk8, 4932438H23Rik, Slc6a13, Avil, Socs2, Smco4, Ier3, Lxn, Gpr171, Adk and Gata1.

In one example embodiment, the method comprises administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity of one or more biological programs characterized by T Cell Topic 5, wherein T cell Topic 5 comprises one or more genes or polypeptides selected from the group consisting of: 1700061F12Rik, Il13, Scin, Lgmn, Hlf, Smco4, Npnt, Il17rb, Deptor, Gata3, Gm2a, Il6, Il17a, Ltb4r1, Fgl2, Areg, Fbxl21, AA467197, Il1rl1, Me1, Gm5544, Tmem159, Rasgrp4, 1700012B07Rik, 1700113H08Rik, St6galnac5, Il4, Chdh, Slco2b1, Ccr9, Epas1, Grp, Lztfl1, Gm10369, Kif19a, Tenm4, Serpinf1, Gnb2, Ubox5, Plcl1, Rab31, Ffar2, Slx1b, Asb2, Zfp85, Tmsb4x, Hdc, Pxdc1, Heatr1 and Lgals7.

In one example embodiment, the method comprises administering to a population of cells comprising ILC2s, mast cells, Th2 cells and/or fibroblasts one or more agents capable of modulating expression, activity of one or more biological programs characterized by stromal cell Topic 4, wherein stromal cell Topic 4 comprises one or more genes or polypeptides selected from the group consisting of: Ccl21a, Cxcl13, Clu, Ccl19, Acta2, Mfge8, Apoe, Tagln, Cxcl1, Cilp, Ccl2, Il33, Cxcl12, Actg2, Serpina3n, Ccl7, Bst1, Serpina1a, Fmod, Grem1, Serpina1b, Slc36a2, Cnn1, Myh11, Art2b, Actc1, AI838599, Serpina1c, Cr2, Gxylt2, Crym, Dclk1, Serpina1d, Myl9, Parm1, Gm16685, Postn, Chrdl1, Colq, Csn2, Prss12, H2-M2, Trf, Sostdc1, Dsc3, Ctgf, Thbs4, Pcdh15, Rtn4r and A230065H16Rik.

In certain example embodiments, the agent suppresses one of the above biological programs, whereby an ILC2 inflammatory response is decreased. The one or more agents may comprise agent(s) that modulate the expression, activity or function of one or more genes of or polypeptides in ILC Topic 2, myeloid cell Topic 1, T cell Topic 5 or stromal cell Topic 4.

In certain example embodiments, the population of cells is in vivo. In certain embodiments, the in vivo population is present in the gut of a subject. In other example embodiments, the population of cell is an in vitro or ex vivo population of cells. In certain other example embodiments, the population of cells is an intestinal organoid.

Modulation and Modulating Agents

As used herein, “modulating” or “to modulate” generally means either reducing or inhibiting the expression or activity of, or alternatively increasing the expression or activity of a target or antigen (e.g., CGRP). In particular, “modulating” or “to modulate” can mean either reducing or inhibiting the activity of, or alternatively increasing a (relevant or intended) biological activity of, a target or antigen as measured using a suitable in vitro, cellular or in vivo assay (which will usually depend on the target involved), by at least 5%, at least 10%, at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or more, compared to activity of the target in the same assay under the same conditions but without the presence of an agent. An “increase” or “decrease” refers to a statistically significant increase or decrease respectively. For the avoidance of doubt, an increase or decrease will be at least 10% relative to a reference, such as at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 97%, at least 98%, or more, up to and including at least 100% or more, in the case of an increase, for example, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 50-fold, at least 100-fold, or more. “Modulating” can also involve effecting a change (which can either be an increase or a decrease) in affinity, avidity, specificity and/or selectivity of a target or antigen, such as CGRP. “Modulating” can also mean effecting a change with respect to one or more biological or physiological mechanisms, effects, responses, functions, pathways or activities in which the target or antigen (or in which its substrate(s), ligand(s) or pathway(s) are involved, such as its signaling pathway or metabolic pathway and their associated biological or physiological effects) is involved. Again, as will be clear to the skilled person, such an action as an agonist or an antagonist can be determined in any suitable manner and/or using any suitable assay known or described herein (e.g., in vitro or cellular assay), depending on the target or antigen involved.

Modulating can, for example, also involve allosteric modulation of the target and/or reducing or inhibiting the binding of the target to one of its substrates or ligands and/or competing with a natural ligand, substrate for binding to the target. Modulating can also involve activating the target or the mechanism or pathway in which it is involved. Modulating can for example also involve effecting a change in respect of the folding or conformation of the target, or in respect of the ability of the target to fold, to change its conformation (for example, upon binding of a ligand), to associate with other (sub)units, or to disassociate. Modulating can for example also involve effecting a change in the ability of the target to signal, phosphorylate, dephosphorylate, and the like.

As used herein, an “agent” can refer to a protein-binding agent that permits modulation of activity of proteins or disrupts interactions of proteins and other biomolecules, such as but not limited to disrupting protein-protein interaction, ligand-receptor interaction, or protein-nucleic acid interaction. Agents can also refer to DNA targeting or RNA targeting agents. Agents can also refer to a protein, such as CGRP. Agents may include a fragment, derivative and analog of an active agent. The terms “fragment,” “derivative” and “analog” when referring to polypeptides as used herein refers to polypeptides which either retain substantially the same biological function or activity as such polypeptides. An analog includes a proprotein which can be activated by cleavage of the proprotein portion to produce an active mature polypeptide. Such agents include, but are not limited to, antibodies (“antibodies” includes antigen-binding portions of antibodies such as epitope- or antigen-binding peptides, paratopes, functional CDRs; recombinant antibodies; chimeric antibodies; humanized antibodies; nanobodies; tribodies; midibodies; or antigen-binding derivatives, analogs, variants, portions, or fragments thereof), protein-binding agents, nucleic acid molecules, small molecules, recombinant protein, peptides, aptamers, avimers and protein-binding derivatives, portions or fragments thereof. An “agent” as used herein, may also refer to an agent that inhibits expression of a gene, such as but not limited to a DNA targeting agent (e.g., CRISPR system, TALE, Zinc finger protein) or RNA targeting agent (e.g., inhibitory nucleic acid molecules such as RNAi, miRNA, ribozyme).

In certain embodiments, the agent modulates CGRP signaling. In certain embodiments, the agent is an agonist or antagonist of CGRP receptor activity. The term “agonist of the CGRP receptor” may refer to a compound that binds to a CGRP receptor and activates said CGRP receptor (see, e.g., US Patent Publication No. 2016-0106813A1).

In certain embodiments, administration of CGRP provokes migraine attacks due to its vasodilation properties, which are associated with dilation of both the middle meningeal artery (MMA), a major artery that supplies blood to a membrane (dura) that envelops the brain, and the middle cerebral artery (MCA) (see, e.g., Silberstein et al., Fremanezumab for the Preventive Treatment of Chronic Migraine, N Engl J Med 2017; 377:2113-22). Several approaches are possible to diminish the potential side-effects of the compounds of the invention. These side-effects can be diminished by following a specific treatment scheme, more precisely by making sure that the consecutive administrations are separated by enough time without CGRP and/or agonist of the CGRP receptor treatment. In a particular embodiment, the consecutive administrations of CGRP and/or agonist of the CGRP receptor are separated by at least 1 day, preferably 2 days, yet preferably 5 days.

The composition of the invention can also advantageously be formulated in order to release CGRP and/or agonist of the CGRP receptor in the subject in a timely controlled fashion. In a particular embodiment, the composition of the invention is formulated for controlled release of CGRP and/or agonist of the CGRP receptor.

In certain embodiments, the agent is capable of inhibiting the CGRP receptor or blocking CGRP receptor interaction with CGRP. Such agents may also be referred to as CGRP receptor antagonists. In certain embodiments, CGRP receptor or CGRP expression is inhibited, e.g., by a DNA targeting agent (e.g., CRISPR system, TALE, Zinc finger protein) or an RNA targeting agent (e.g., inhibitory nucleic acid molecules). In some embodiments, CGRP receptor activity is inhibited. Such inhibition includes, e.g., reducing the expression of its ligand, CGRP, or by blocking the interaction of CGRP receptor with CGRP. In certain embodiments, the antagonist is an antibody or fragment thereof. In certain embodiments, the antibody is specific for CGRP or CGRP receptor.

The agents of the present invention may be modified, such that they acquire advantageous properties for therapeutic use (e.g., stability and specificity), but maintain their biological activity (see, also administration).

It is well known that the properties of certain proteins can be modulated by attachment of polyethylene glycol (PEG) polymers, which increases the hydrodynamic volume of the protein and thereby slows its clearance by kidney filtration. (See, e.g., Clark et al., J. Biol. Chem. 271: 21969-21977 (1996)). Therefore, it is envisioned that certain agents can be PEGylated (e.g., on peptide residues) to provide enhanced therapeutic benefits such as, for example, increased efficacy by extending half-life in vivo. In certain embodiments, PEGylation of the agents may be used to extend the serum half-life of the agents (e.g., CGRP) and allow for particular agents to be capable of crossing the blood-brain barrier. Thus, in one embodiment, PEGylating CGRP or the CGRP receptor agonists or antagonists improve the pharmacokinetics and pharmacodynamics of the CGRP receptor agonists or antagonists.

In regards to peptide PEGylation methods, reference is made to Lu et al., Int. J. Pept. Protein Res. 43: 127-38 (1994); Lu et al., Pept. Res. 6: 140-6 (1993); Felix et al., Int. J. Pept. Protein Res. 46: 253-64 (1995); Gaertner et al., Bioconjug. Chem. 7: 38-44 (1996); Tsutsumi et al., Thromb. Haemost. 77: 168-73 (1997); Francis et al., hit. J. Hematol. 68: 1-18 (1998); Roberts et al., J. Pharm. Sci. 87: 1440-45 (1998); and Tan et al., Protein Expr. Purif. 12: 45-52 (1998). Polyethylene glycol or PEG is meant to encompass any of the forms of PEG that have been used to derivatize other proteins, including, but not limited to, mono-(C1-10) alkoxy or aryloxy-polyethylene glycol. Suitable PEG moieties include, for example, 40 kDa methoxy poly(ethylene glycol) propionaldehyde (Dow, Midland, Mich.); 60 kDa methoxy poly(ethylene glycol) propionaldehyde (Dow, Midland, Mich.); 40 kDa methoxy poly(ethylene glycol) maleimido-propionamide (Dow, Midland, Mich.); 31 kDa alpha-methyl-w-(3-oxopropoxy), polyoxyethylene (NOF Corporation, Tokyo); mPEG2-NHS-40k (Nektar); mPEG2-MAL-40k (Nektar), SUNBRIGHT GL2-400MA ((PEG)240 kDa) (NOF Corporation, Tokyo), SUNBRIGHT ME-200MA (PEG20 kDa) (NOF Corporation, Tokyo). The PEG groups are generally attached to the peptide (e.g., CGRP) via acylation or alkylation through a reactive group on the PEG moiety (for example, a maleimide, an aldehyde, amino, thiol, or ester group) to a reactive group on the peptide (for example, an aldehyde, amino, thiol, a maleimide, or ester group).

The PEG molecule(s) may be covalently attached to any Lys, Cys, or K(CO(CH2)₂SH) residues at any position in a peptide. In certain embodiments, the CGRP receptor agonists described herein can be PEGylated directly to any amino acid at the N-terminus by way of the N-terminal amino group. A “linker arm” may be added to a peptide to facilitate PEGylation. PEGylation at the thiol side-chain of cysteine has been widely reported (see, e.g., Caliceti & Veronese, Adv. Drug Deliv. Rev. 55: 1261-77 (2003)). If there is no cysteine residue in the peptide, a cysteine residue can be introduced through substitution or by adding a cysteine to the N-terminal amino acid. In certain embodiments, CGRP receptor agonists are PEGylated through the side chains of a cysteine residue added to the N-terminal amino acid.

In exemplary embodiments, the PEG molecule(s) may be covalently attached to an amide group in the C-terminus of a peptide, such as in the CGRP receptor agonist. In preferred embodiments, there is at least one PEG molecule covalently attached to the CGRP receptor agonist. In certain embodiments, the PEG molecule used in modifying an agent of the present invention is branched while in other embodiments, the PEG molecule may be linear. In particular aspects, the PEG molecule is between 1 kDa and 100 kDa in molecular weight. In further aspects, the PEG molecule is selected from 10, 20, 30, 40, 50, 60, and 80 kDa. In further still aspects, it is selected from 20, 40, or 60 kDa. Where there are two PEG molecules covalently attached to the agent of the present invention, each is 1 to 40 kDa and in particular aspects, they have molecular weights of 20 and 20 kDa, 10 and 30 kDa, 30 and 30 kDa, 20 and 40 kDa, or 40 and 40 kDa. In particular aspects, the agent (e.g., CGRP receptor agonists or antagonists) contain mPEG-cysteine. The mPEG in mPEG-cysteine can have various molecular weights. The range of the molecular weight is preferably 5 kDa to 200 kDa, more preferably 5 kDa to 100 kDa, and further preferably 20 kDa to 60 kDA. The mPEG can be linear or branched.

In particular embodiments, the agents (e.g., CGRP, or CGRP agonist or antagonists) include a protecting group covalently joined to the N-terminal amino group. In exemplary embodiments, a protecting group covalently joined to the N-terminal amino group of the CGRP receptor agonists reduces the reactivity of the amino terminus under in vivo conditions. Amino protecting groups include —C1-10 alkyl, —C1-10 substituted alkyl, —C2-10 alkenyl, —C2-10 substituted alkenyl, aryl, —C1-6 alkyl aryl, —C(O)—(CH2)1-6-COOH, —C(O)—C1-6 alkyl, —C(O)-aryl, —C(O)—O—C1-6 alkyl, or —C(O)—O-aryl. In particular embodiments, the amino terminus protecting group is selected from the group consisting of acetyl, propyl, succinyl, benzyl, benzyloxycarbonyl, and t-butyloxycarbonyl. In other embodiments, deamination of the N-terminal amino acid is another modification that may be used for reducing the reactivity of the amino terminus under in vivo conditions.

Chemically modified compositions of the agents (e.g., CGRP, or CGRP receptor agonists or antagonists) wherein the agent is linked to a polymer are also included within the scope of the present invention. The polymer selected is usually modified to have a single reactive group, such as an active ester for acylation or an aldehyde for alkylation, so that the degree of polymerization may be controlled. Included within the scope of polymers is a mixture of polymers. Preferably, for therapeutic use of the end-product preparation, the polymer will be pharmaceutically acceptable. The polymer or mixture thereof may include but is not limited to polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, or other carbohydrate-based polymers, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, a polypropylene oxide/ethylene oxide co-polymer, polyoxyethylated polyols (for example, glycerol), and polyvinyl alcohol.

In other embodiments, the agents (e.g., CGRP receptor agonists or antagonists) are modified by PEGylation, cholesterylation, or palmitoylation. The modification can be to any amino acid residue. In preferred embodiments, the modification is to the N-terminal amino acid of the agent (e.g., CGRP receptor agonist or antagonists), either directly to the N-terminal amino acid or by way coupling to the thiol group of a cysteine residue added to the N-terminus or a linker added to the N-terminus such as trimesoyl tris(3,5-dibromosalicylate (Ttds). In certain embodiments, the N-terminus of the agent (e.g., CGRP receptor agonist or antagonist) comprises a cysteine residue to which a protecting group is coupled to the N-terminal amino group of the cysteine residue and the cysteine thiolate group is derivatized with N-ethylmaleimide, PEG group, cholesterol group, or palmitoyl group. In other embodiments, an acetylated cysteine residue is added to the N-terminus of the agents, and the thiol group of the cysteine is derivatized with N-ethylmaleimide, PEG group, cholesterol group, or palmitoyl group. In certain embodiments, the agent of the present invention is a conjugate. In certain embodiments, the agent of the present invention (e.g., CGRP receptor agonists or antagonists) is a polypeptide consisting of an amino acid sequence which is bound with a methoxypolyethylene glycol(s) via a linker.

Substitutions of amino acids may be used to modify an agent of the present invention. The phrase “substitution of amino acids” as used herein encompasses substitution of amino acids that are the result of both conservative and non-conservative substitutions. Conservative substitutions are the replacement of an amino acid residue by another similar residue in a polypeptide. Typical but not limiting conservative substitutions are the replacements, for one another, among the aliphatic amino acids Ala, Val, Leu and Ile; interchange of Ser and Thr containing hydroxy residues, interchange of the acidic residues Asp and Glu, interchange between the amide-containing residues Asn and Gln, interchange of the basic residues Lys and Arg, interchange of the aromatic residues Phe and Tyr, and interchange of the small-sized amino acids Ala, Ser, Thr, Met, and Gly. Non-conservative substitutions are the replacement, in a polypeptide, of an amino acid residue by another residue which is not biologically similar. For example, the replacement of an amino acid residue with another residue that has a substantially different charge, a substantially different hydrophobicity, or a substantially different spatial configuration.

In certain embodiments, the present invention provides for one or more therapeutic agents. In certain embodiments, the one or more agents comprises a small molecule inhibitor, small molecule degrader (e.g., PROTAC), genetic modifying agent, antibody, antibody fragment, antibody-like protein scaffold, aptamer, protein, or any combination thereof.

The terms “therapeutic agent”, “therapeutic capable agent” or “treatment agent” are used interchangeably and refer to a molecule or compound that confers some beneficial effect upon administration to a subject. The beneficial effect includes enablement of diagnostic determinations; amelioration of a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder or condition; and generally counteracting a disease, symptom, disorder or pathological condition.

As used herein, “treatment” or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to a therapeutic benefit and/or a prophylactic benefit. By therapeutic benefit is meant any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment. For prophylactic benefit, the compositions may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more of the physiological symptoms of a disease, even though the disease, condition, or symptom may not have yet been manifested. As used herein “treating” includes ameliorating, curing, preventing it from becoming worse, slowing the rate of progression, or preventing the disorder from re-occurring (i.e., to prevent a relapse). In certain embodiments, the present invention provides for one or more therapeutic agents against combinations of targets identified. Targeting the identified combinations may provide for enhanced or otherwise previously unknown activity in the treatment of disease.

Small Molecules

In certain embodiments, the one or more agents is a small molecule. The term “small molecule” refers to compounds, preferably organic compounds, with a size comparable to those organic molecules generally used in pharmaceuticals. The term excludes biological macromolecules (e.g., proteins, peptides, nucleic acids, etc.). Preferred small organic molecules range in size up to about 5000 Da, e.g., up to about 4000, preferably up to 3000 Da, more preferably up to 2000 Da, even more preferably up to about 1000 Da, e.g., up to about 900, 800, 700, 600 or up to about 500 Da. In certain embodiments, the small molecule may act as an antagonist or agonist (e.g., blocking a binding site or activating a receptor by binding to a ligand binding site).

One type of small molecule applicable to the present invention is a degrader molecule. Proteolysis Targeting Chimera (PROTAC) technology is a rapidly emerging alternative therapeutic strategy with the potential to address many of the challenges currently faced in modern drug development programs. PROTAC technology employs small molecules that recruit target proteins for ubiquitination and removal by the proteasome (see, e.g., Zhou et al., Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J. Med. Chem. 2018, 61, 462-481; Bondeson and Crews, Targeted Protein Degradation by Small Molecules, Annu Rev Pharmacol Toxicol. 2017 Jan. 6; 57: 107-123; and Lai et al., Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL Angew Chem Int Ed Engl. 2016 Jan. 11; 55(2): 807-810).

In certain embodiments, combinations of targets are modulated (e.g., CGRP and one or more targets related to a gene signature gene). In certain embodiments, an agent against one of the targets in a combination may already be known or used clinically. In certain embodiments, targeting the combination may require less of the agent as compared to the current standard of care and provide for less toxicity and improved treatment.

GPR65

In certain example embodiments, the agent is an agent that modulates GPR65, also known as T cell death-associated gene 8 (TDAG8) is a G protein-coupled receptor (GPCR) protein that in humans is encoded by the GPR65 gene. GPR65 senses extracellular pH. It was found that cAMP levels increased when GPR65 was stimulated by pH values less than pH 7.2. Recent studies disclose that TDAG8 (GPR65) inhibits intestinal inflammation in the dss-induced experimental colitis mouse model (Sanderlin, et al., 2018, TDAG8 (GPR65) Inhibits Intestinal Inflammation in the DSS-Induced Experimental Colitis Mouse Model, bioRxiv 496315; doi.org/10.1101/496315). TDAG8-null mice showed exacerbation of intestinal inflammation and fibrosis. id. Aberrant TDAG8 function is associated with IBD development and progression (Jostins, et al., Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119-124, 2012; and Lassen, et al., Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk. Immunity, 2016). Applicants have shown for the first time that CGRP induces expression of GPR65 in ILC2s and suppresses type 2 inflammation-induced activation and expansion of intestinal ILC2s through activation of a cAMP response module. In certain embodiments, combination treatment with GPR65 agonists and agonists of CGRP signaling (e.g., CGRP) can be used in the treatment of or prevention of ILC2 inflammatory responses.

A GPR65 agonist, BTB09089 ((3-[(2,4-dichlorobenzyl)thio]-1,6-dimethyl-5,6-dihydro-1H-pyridazino[4,5-e][1,3,4]thiadiazin-5-one), has been developed and recently investigated for anti-inflammatory properties. In one study, BTB09089 was shown to activate TDAG8 in vitro (Onozawa, et al., Activation of T cell death associated gene 8 regulates the cytokine production of T cells and macrophages in vitro. Eur J Pharmacol 683: 325-331, 2012). An additional study has shown in vivo efficacy of BTB09089 using an ischemic stroke murine disease model (Ma et al., TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats. Exp Neurol 293: 115-123, 2017). In certain embodiments, CGRP is administered in combination with BTB09089 or similar molecules (see, e.g., pubchem.ncbi.nlm.nih.gov/compound/2801217). Additionally, allosteric agonists and negative allosteric modulators (NAMs) for GPR65 applicable to the present invention have been identified (ZINC62678696) (see, e.g., Huang, et al., Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65, Nature. 2015 Nov. 26; 527(7579): 477-483).

PDCD1

PDCD1 is the human gene encoding the immune checkpoint protein PD-1. Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. Modulating immune checkpoint activity in response to upregulation by CGRP may reduce an ILC2 inflammatory response or maintain homeostasis. In certain embodiments, a combination treatment may include CGRP and a checkpoint agonist. Checkpoint proteins may include TIM3, CTLA4, or PD-1. Immune checkpoint agonists may activate checkpoint signaling, for example, by binding to the checkpoint protein. The agonists may include a ligand (e.g., PD-L1). PD-1 agonist antibodies that mimic PD-1 ligand (PD-L1) have been described (see, e.g., US20170088618A1; WO2018053405A1). Such agonist antibodies against any receptor described herein are applicable to the present invention.

Adenylate Cyclase Activators

In certain embodiments, the one or more modulating agents comprises an adenylate cyclase activator. The adenylate cyclase activator may be forskolin, Other non-limiting examples of adenylate cyclase activators applicable to present invention include forskolin derivatives, an extract of Coleus forskohlii having adenylate cyclase activator activity, carbacyclin, isoproterenol, prostaglandin D₂, prostaglandin Ei and prostaglandin I₂(prostacyclin). As used herein, “Forskolin” refers to a labdane diterpene that is produced by the Indian Coleus plant (Coleus forskohlii, aka Plectranthus barbatus). Forskolin is commonly used to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology. A number of structural variants of forskolin are known in the art and may be referred to herein as forskolin derivatives, for example those described in Kokic, Curr Med Chem Cardiovasc Hematol Agents. 2005 October; 3(4):333-9; Gao et al, Mini Rev Med Chem. 2005 June; 5(6):545-53; Head, Altern Med Rev. 2001 April; 6(2): 141-66; Zidek, Eur Cytokine Netw. 2001 March; 12(1):22-32; Ong et al., Acta Pharmacol Sin. 2000 February; 21(2):111-23; Chen et al., Lab Invest. 1998 February; 78(2):165-74; Milligan et al., Receptors Channels. 1997; 5(3-4):209-13; Sulakhe et al. Mol Cell Biochem. 1995 August-September; 149-150:103-26; Ehlert et al., Life Sci. 1995; 56(11-12):965-71; and Farah et al., Annu Rev Pharmacol Toxicol. 1984; 24:275-328. Preparation, including solubilization, and use of forskolin and related compounds including forskolin derivatives, are described in, e.g., U.S. Pat. No. 6,960,300 and in Chen et al., 2009 J. Nat. Prod. 72:769. Adenylate cyclase activators may also include those disclosed in U.S. Pat. No. 6,333,354.

Antibodies

The term “antibody” (e.g., anti-CGRP or anti-CGRP receptor antibody) is used interchangeably with the term “immunoglobulin” herein, and includes intact antibodies, fragments of antibodies, e.g., Fab, F(ab′)2 fragments, and intact antibodies and fragments that have been mutated either in their constant and/or variable region (e.g., mutations to produce chimeric, partially humanized, or fully humanized antibodies, as well as to produce antibodies with a desired trait, e.g., enhanced binding and/or reduced FcR binding). The term “fragment” refers to a part or portion of an antibody or antibody chain comprising fewer amino acid residues than an intact or complete antibody or antibody chain. Fragments can be obtained via chemical or enzymatic treatment of an intact or complete antibody or antibody chain. Fragments can also be obtained by recombinant means. Exemplary fragments include Fab, Fab′, F(ab′)2, Fabc, Fd, dAb, V_HHand scFv and/or Fv fragments.

As used herein, a preparation of antibody protein having less than about 50% of non-antibody protein (also referred to herein as a “contaminating protein”), or of chemical precursors, is considered to be “substantially free.” 40%, 30%, 20%, 10% and more preferably 5% (by dry weight), of non-antibody protein, or of chemical precursors is considered to be substantially free. When the antibody protein or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 30%, preferably less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume or mass of the protein preparation.

The term “antigen-binding fragment” refers to a polypeptide fragment of an immunoglobulin or antibody that binds antigen or competes with intact antibody (i.e., with the intact antibody from which they were derived) for antigen binding (i.e., specific binding). As such these antibodies or fragments thereof are included in the scope of the invention, provided that the antibody or fragment binds specifically to a target molecule.

It is intended that the term “antibody” encompass any Ig class or any Ig subclass (e.g. the IgG1, IgG2, IgG3, and IgG4 subclassess of IgG) obtained from any source (e.g., humans and non-human primates, and in rodents, lagomorphs, caprines, bovines, equines, ovines, etc.).

The term “Ig class” or “immunoglobulin class”, as used herein, refers to the five classes of immunoglobulin that have been identified in humans and higher mammals, IgG, IgM, IgA, IgD, and IgE. The term “Ig subclass” refers to the two subclasses of IgM (H and L), three subclasses of IgA (IgA1, IgA2, and secretory IgA), and four subclasses of IgG (IgG1, IgG2, IgG3, and IgG4) that have been identified in humans and higher mammals. The antibodies can exist in monomeric or polymeric form; for example, lgM antibodies exist in pentameric form, and IgA antibodies exist in monomeric, dimeric or multimeric form.

The term “IgG subclass” refers to the four subclasses of immunoglobulin class IgG-IgG1, IgG2, IgG3, and IgG4 that have been identified in humans and higher mammals by the heavy chains of the immunoglobulins, V1-γ4, respectively. The term “single-chain immunoglobulin” or “single-chain antibody” (used interchangeably herein) refers to a protein having a two-polypeptide chain structure consisting of a heavy and a light chain, said chains being stabilized, for example, by interchain peptide linkers, which has the ability to specifically bind antigen. The term “domain” refers to a globular region of a heavy or light chain polypeptide comprising peptide loops (e.g., comprising 3 to 4 peptide loops) stabilized, for example, by β pleated sheet and/or intrachain disulfide bond. Domains are further referred to herein as “constant” or “variable”, based on the relative lack of sequence variation within the domains of various class members in the case of a “constant” domain, or the significant variation within the domains of various class members in the case of a “variable” domain. Antibody or polypeptide “domains” are often referred to interchangeably in the art as antibody or polypeptide “regions”. The “constant” domains of an antibody light chain are referred to interchangeably as “light chain constant regions”, “light chain constant domains”, “CL” regions or “CL” domains. The “constant” domains of an antibody heavy chain are referred to interchangeably as “heavy chain constant regions”, “heavy chain constant domains”, “CH” regions or “CH” domains). The “variable” domains of an antibody light chain are referred to interchangeably as “light chain variable regions”, “light chain variable domains”, “VL” regions or “VL” domains). The “variable” domains of an antibody heavy chain are referred to interchangeably as “heavy chain constant regions”, “heavy chain constant domains”, “VH” regions or “VH” domains).

The term “region” can also refer to a part or portion of an antibody chain or antibody chain domain (e.g., a part or portion of a heavy or light chain or a part or portion of a constant or variable domain, as defined herein), as well as more discrete parts or portions of said chains or domains. For example, light and heavy chains or light and heavy chain variable domains include “complementarity determining regions” or “CDRs” interspersed among “framework regions” or “FRs”, as defined herein.

The term “conformation” refers to the tertiary structure of a protein or polypeptide (e.g., an antibody, antibody chain, domain or region thereof). For example, the phrase “light (or heavy) chain conformation” refers to the tertiary structure of a light (or heavy) chain variable region, and the phrase “antibody conformation” or “antibody fragment conformation” refers to the tertiary structure of an antibody or fragment thereof.

The term “antibody-like protein scaffolds” or “engineered protein scaffolds” broadly encompasses proteinaceous non-immunoglobulin specific-binding agents, typically obtained by combinatorial engineering (such as site-directed random mutagenesis in combination with phage display or other molecular selection techniques). Usually, such scaffolds are derived from robust and small soluble monomeric proteins (such as Kunitz inhibitors or lipocalins) or from a stably folded extra-membrane domain of a cell surface receptor (such as protein A, fibronectin or the ankyrin repeat).

Such scaffolds have been extensively reviewed in Binz et al. (Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol 2005, 23:1257-1268), Gebauer and Skerra (Engineered protein scaffolds as next-generation antibody therapeutics. Curr Opin Chem Biol. 2009, 13:245-55), Gill and Damle (Biopharmaceutical drug discovery using novel protein scaffolds. Curr Opin Biotechnol 2006, 17:653-658), Skerra (Engineered protein scaffolds for molecular recognition. J Mol Recognit 2000, 13:167-187), and Skerra (Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol 2007, 18:295-304), and include without limitation affibodies, based on the Z-domain of staphylococcal protein A, a three-helix bundle of 58 residues providing an interface on two of its alpha-helices (Nygren, Alternative binding proteins: Affibody binding proteins developed from a small three-helix bundle scaffold. FEBS J 2008, 275:2668-2676); engineered Kunitz domains based on a small (ca. 58 residues) and robust, disulphide-crosslinked serine protease inhibitor, typically of human origin (e.g. LACI-D1), which can be engineered for different protease specificities (Nixon and Wood, Engineered protein inhibitors of proteases. Curr Opin Drug Discov Dev 2006, 9:261-268); monobodies or adnectins based on the 10th extracellular domain of human fibronectin III (10Fn3), which adopts an Ig-like beta-sandwich fold (94 residues) with 2-3 exposed loops, but lacks the central disulphide bridge (Koide and Koide, Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain. Methods Mol Biol 2007, 352:95-109); anticalins derived from the lipocalins, a diverse family of eight-stranded beta-barrel proteins (ca. 180 residues) that naturally form binding sites for small ligands by means of four structurally variable loops at the open end, which are abundant in humans, insects, and many other organisms (Skerra, Alternative binding proteins: Anticalins-harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities. FEBS J 2008, 275:2677-2683); DARPins, designed ankyrin repeat domains (166 residues), which provide a rigid interface arising from typically three repeated beta-turns (Stumpp et al., DARPins: a new generation of protein therapeutics. Drug Discov Today 2008, 13:695-701); avimers (multimerized LDLR-A module) (Silverman et al., Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains. Nat Biotechnol 2005, 23:1556-1561); and cysteine-rich knottin peptides (Kolmar, Alternative binding proteins: biological activity and therapeutic potential of cystine-knot miniproteins. FEBS J 2008, 275:2684-2690).

“Specific binding” of an antibody means that the antibody exhibits appreciable affinity for a particular antigen or epitope and, generally, does not exhibit significant cross reactivity. “Appreciable” binding includes binding with an affinity of at least 25 μM. Antibodies with affinities greater than 1×10⁷M⁻¹(or a dissociation coefficient of 1 μM or less or a dissociation coefficient of 1 nm or less) typically bind with correspondingly greater specificity. Values intermediate of those set forth herein are also intended to be within the scope of the present invention and antibodies of the invention bind with a range of affinities, for example, 100 nM or less, 75 nM or less, 50 nM or less, 25 nM or less, for example 10 nM or less, 5 nM or less, 1 nM or less, or in embodiments 500 pM or less, 100 pM or less, 50 pM or less or 25 pM or less. An antibody that “does not exhibit significant crossreactivity” is one that will not appreciably bind to an entity other than its target (e.g., a different epitope or a different molecule). For example, an antibody that specifically binds to a target molecule will appreciably bind the target molecule but will not significantly react with non-target molecules or peptides. An antibody specific for a particular epitope will, for example, not significantly crossreact with remote epitopes on the same protein or peptide. Specific binding can be determined according to any art-recognized means for determining such binding. Preferably, specific binding is determined according to Scatchard analysis and/or competitive binding assays.

As used herein, the term “affinity” refers to the strength of the binding of a single antigen-combining site with an antigenic determinant. Affinity depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, on the distribution of charged and hydrophobic groups, etc. Antibody affinity can be measured by equilibrium dialysis or by the kinetic BIACORE™ method. The dissociation constant, Kd, and the association constant, Ka, are quantitative measures of affinity.

As used herein, the term “monoclonal antibody” refers to an antibody derived from a clonal population of antibody-producing cells (e.g., B lymphocytes or B cells) which is homogeneous in structure and antigen specificity. The term “polyclonal antibody” refers to a plurality of antibodies originating from different clonal populations of antibody-producing cells which are heterogeneous in their structure and epitope specificity but which recognize a common antigen. Monoclonal and polyclonal antibodies may exist within bodily fluids, as crude preparations, or may be purified, as described herein.

The term “binding portion” of an antibody (or “antibody portion”) includes one or more complete domains, e.g., a pair of complete domains, as well as fragments of an antibody that retain the ability to specifically bind to a target molecule. It has been shown that the binding function of an antibody can be performed by fragments of a full-length antibody. Binding fragments are produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins. Binding fragments include Fab, Fab′, F(ab′)2, Fabc, Fd, dAb, Fv, single chains, single-chain antibodies, e.g., scFv, and single domain antibodies.

“Humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity. In some instances, FR residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.

Examples of portions of antibodies or epitope-binding proteins encompassed by the present definition include: (i) the Fab fragment, having V_L, C_L, V_Hand CH1 domains; (ii) the Fab′ fragment, which is a Fab fragment having one or more cysteine residues at the C-terminus of the C_H1 domain; (iii) the Fd fragment having VH and CH1 domains; (iv) the Fd′ fragment having V_Hand CH1 domains and one or more cysteine residues at the C-terminus of the CHI domain; (v) the Fv fragment having the V_Land V_Hdomains of a single arm of an antibody; (vi) the dAb fragment (Ward et al., 341 Nature 544 (1989)) which consists of a V_Hdomain or a V_Ldomain that binds antigen; (vii) isolated CDR regions or isolated CDR regions presented in a functional framework; (viii) F(ab′)₂fragments which are bivalent fragments including two Fab′ fragments linked by a disulphide bridge at the hinge region; (ix) single chain antibody molecules (e.g., single chain Fv; scFv) (Bird et al., 242 Science 423 (1988); and Huston et al., 85 PNAS 5879 (1988)); (x) “diabodies” with two antigen binding sites, comprising a heavy chain variable domain (V_H) connected to a light chain variable domain (V_L) in the same polypeptide chain (see, e.g., EP 404,097; International Patent Publication No. WO 93/11161; Hollinger et al., 90 PNAS 6444 (1993)); (xi) “linear antibodies” comprising a pair of tandem Fd segments (V_H-C_h1-V_H-C_h1) which, together with complementary light chain polypeptides, form a pair of antigen binding regions (Zapata et al., Protein Eng. 8(10):1057-62 (1995); and U.S. Pat. No. 5,641,870).

As used herein, a “blocking” antibody or an antibody “antagonist” is one which inhibits or reduces biological activity of the antigen(s) it binds. For example, an antagonist antibody may bind CGRP receptor or CGRP and inhibit the ability to suppress an ILC class 2 inflammatory response. In certain embodiments, the blocking antibodies or antagonist antibodies or portions thereof described herein completely inhibit the biological activity of the antigen(s).

Antibodies may act as agonists or antagonists of the recognized polypeptides. For example, the present invention includes antibodies which disrupt receptor/ligand interactions either partially or fully. The invention features both receptor-specific antibodies and ligand-specific antibodies. The invention also features receptor-specific antibodies which do not prevent ligand binding but prevent receptor activation. Receptor activation (i.e., signaling) may be determined by techniques described herein or otherwise known in the art. For example, receptor activation can be determined by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or of one of its down-stream substrates by immunoprecipitation followed by western blot analysis. In specific embodiments, antibodies are provided that inhibit ligand activity or receptor activity by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 60%, or at least 50% of the activity in absence of the antibody.

The invention also features receptor-specific antibodies which both prevent ligand binding and receptor activation as well as antibodies that recognize the receptor-ligand complex. Likewise, encompassed by the invention are neutralizing antibodies which bind the ligand and prevent binding of the ligand to the receptor, as well as antibodies which bind the ligand, thereby preventing receptor activation, but do not prevent the ligand from binding the receptor. Further included in the invention are antibodies which activate the receptor. These antibodies may act as receptor agonists, i.e., potentiate or activate either all or a subset of the biological activities of the ligand-mediated receptor activation, for example, by inducing dimerization of the receptor. The antibodies may be specified as agonists, antagonists or inverse agonists for biological activities comprising the specific biological activities of the peptides disclosed herein. The antibody agonists and antagonists can be made using methods known in the art. See, e.g., International Patent Publication No. WO 96/40281; U.S. Pat. No. 5,811,097; Deng et al., Blood 92(6):1981-1988 (1998); Chen et al., Cancer Res. 58(16):3668-3678 (1998); Harrop et al., J. Immunol. 161(4):1786-1794 (1998); Zhu et al., Cancer Res. 58(15):3209-3214 (1998); Yoon et al., J. Immunol. 160(7):3170-3179 (1998); Prat et al., J. Cell. Sci. III (Pt2):237-247 (1998); Pitard et al., J. Immunol. Methods 205(2):177-190 (1997); Liautard et al., Cytokine 9(4):233-241 (1997); Carlson et al., J. Biol. Chem. 272(17):11295-11301 (1997); Taryman et al., Neuron 14(4):755-762 (1995); Muller et al., Structure 6(9):1153-1167 (1998); Bartunek et al., Cytokine 8(1):14-20 (1996).

The antibodies as defined for the present invention include derivatives that are modified, i.e., by the covalent attachment of any type of molecule to the antibody such that covalent attachment does not prevent the antibody from generating an anti-idiotypic response. For example, but not by way of limitation, the antibody derivatives include antibodies that have been modified, e.g., by glycosylation, acetylation, pegylation, phosphylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. Any of numerous chemical modifications may be carried out by known techniques, including, but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of tunicamycin, etc. Additionally, the derivative may contain one or more non-classical amino acids.

Simple binding assays can be used to screen for or detect agents that bind to a target protein, or disrupt the interaction between proteins (e.g., a receptor and a ligand). Because certain targets of the present invention are transmembrane proteins, assays that use the soluble forms of these proteins rather than full-length protein can be used, in some embodiments. Soluble forms include, for example, those lacking the transmembrane domain and/or those comprising the IgV domain or fragments thereof which retain their ability to bind their cognate binding partners. Further, agents that inhibit or enhance protein interactions for use in the compositions and methods described herein, can include recombinant peptido-mimetics.

Detection methods useful in screening assays include antibody-based methods, detection of a reporter moiety, detection of cytokines as described herein, and detection of a gene signature as described herein.

Another variation of assays to determine binding of a receptor protein to a ligand protein is through the use of affinity biosensor methods. Such methods may be based on the piezoelectric effect, electrochemistry, or optical methods, such as ellipsometry, optical wave guidance, and surface plasmon resonance (SPR).

The disclosure also encompasses nucleic acid molecules, in particular those that inhibit CGRP receptor or CGRP. Exemplary nucleic acid molecules include aptamers, siRNA, artificial microRNA, interfering RNA or RNAi, dsRNA, ribozymes, antisense oligonucleotides, and DNA expression cassettes encoding said nucleic acid molecules. Preferably, the nucleic acid molecule is an antisense oligonucleotide. Antisense oligonucleotides (ASO) generally inhibit their target by binding target mRNA and sterically blocking expression by obstructing the ribosome. ASOs can also inhibit their target by binding target mRNA thus forming a DNA-RNA hybrid that can be a substance for RNase H. Preferred ASOs include Locked Nucleic Acid (LNA), Peptide Nucleic Acid (PNA), and morpholinos Preferably, the nucleic acid molecule is an RNAi molecule, i.e., RNA interference molecule. Preferred RNAi molecules include siRNA, shRNA, and artificial miRNA. The design and production of siRNA molecules is well known to one of skill in the art (e.g., Hajeri P B, Singh S K. Drug Discov Today. 2009 14(17-18):851-8). The nucleic acid molecule inhibitors may be chemically synthesized and provided directly to cells of interest. The nucleic acid compound may be provided to a cell as part of a gene delivery vehicle. Such a vehicle is preferably a liposome or a viral gene delivery vehicle.

Genetic Modifying Agents

In certain embodiments, the one or more modulating agents may be a genetic modifying agent. The genetic modifying agent may comprise a CRISPR system, a zinc finger nuclease system, a TALEN, a meganuclease or RNAi system. The genetic modifying agent preferably modulates expression of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5, preferably, GPR65 and/or PD-1 (e.g., guide sequences designed to target the genes). In certain embodiments, CGRP induces expression of Gpr65, Pdcd1, Crem, Egln3, Adora2a, Rgs2, Gna15, Adrb2, Gadd45a, Areg, Hif1a, Dusp1, Pde4b, Cdkn1a, Akap12 and Il5 to maintain homeostasis of intestinal ILC2 cells. The genetic modifying agent also preferably modulates expression of a cAMP response module, wherein the cAMP module comprises one or more genes selected from the group consisting of: Adrb2, Adora2a, Pde4b, Akap12, Areg, Crem and Il5. The genetic modifying agent also preferably modulates expression of one or more genes in one or more biological programs characterized by ILC Topic 2, myeloid cell Topic 1, T cell Topic 5 or stromal cell Topic 4, wherein ILC Topic 2 comprises one or more genes or polypeptides selected from the group consisting of: Calca, Hs3st1, Areg, Il13, Il4, Ccl1, Hes1, Il17rb, Lgals7, Homer2, Il5, Gata3, Deptor, Ptpn13, Ly6a, Hba-a1, Kcnn4, Ccr4, Rxrg, Sub1, 1700061F12Rik, Cntnap2, AA467197, Ptgir, Il10, Nfkb1, Lmo4, Pparg, Plaur, Il9r, Serpine1, Scel, Bmp7, Neb, Sox8, Lpcat2, Samsn1, Alox5, Gpr65, Abhd17c, Gm20186, Gm973, Epas1, Ccr8, D430036J16Rik, Cd6, Stxbp6, 9230102O04Rik, Furin and Klf5, wherein myeloid cell Topic 1 comprises one or more genes or polypeptides selected from the group consisting of: Cpa3, Cma1, Mcpt4, Tpsb2, Fcer1a, Hs3st1, Gata2, Cited4, Cyp11a1, Tph1, Furin, Rab27b, Slc45a3, Ccl1, Il13, Il1rl1, Itga2b, Cited2, Fam110c, Creb3l1, Rgs13, Tpsab1, Cyp26a1, Serpinb1a, Slc18a2, Gmpr, Rprm, Ero1l, Il4, Cd200r3, Glul, Kit, Lat, Alox5, Gchfr, mt-Atp6, Lat2, Prss34, Poln, Klk8, 4932438H23Rik, Slc6a13, Avil, Socs2, Smco4, Ier3, Lxn, Gpr171, Adk and Gata1, wherein T cell Topic 5 comprises one or more genes or polypeptides selected from the group consisting of: 1700061F12Rik, Il13, Scin, Lgmn, Hlf, Smco4, Npnt, Il17rb, Deptor, Gata3, Gm2a, Il6, Il17a, Ltb4r1, Fgl2, Areg, Fbxl21, AA467197, Il1rl1, Me1, Gm5544, Tmem159, Rasgrp4, 1700012B07Rik, 1700113H08Rik, St6galnac5, Il4, Chdh, Slco2b1, Ccr9, Epas1, Grp, Lztfl1, Gm10369, Kif19a, Tenm4, Serpinf1, Gnb2, Ubox5, Plcl1, Rab31, Ffar2, Slx1b, Asb2, Zfp85, Tmsb4x, Hdc, Pxdc1, Heatr1 and Lgals7, wherein stromal cell Topic 4 comprises one or more genes or polypeptides selected from the group consisting of: Ccl21a, Cxcl13, Clu, Ccl19, Acta2, Mfge8, Apoe, Tagln, Cxcl1, Cilp, Ccl2, Il33, Cxcl12, Actg2, Serpina3n, Ccl7, Bst1, Serpina1a, Fmod, Grem1, Serpina1b, Slc36a2, Cnn1, Myh11, Art2b, Actc1, AI838599, Serpina1c, Cr2, Gxylt2, Crym, Dclk1, Serpina1d, Myl9, Parm1, Gm16685, Postn, Chrdl1, Colq, Csn2, Prss12, H2-M2, Trf, Sostdc1, Dsc3, Ctgf, Thbs4, Pcdh15, Rtn4r and A230065H16Rik. In certain embodiments, the one or more biological programs are suppressed, whereby an ILC2 inflammatory response is decreased.

CRISPR-Cas Modification

In some embodiments, a polynucleotide of the present invention described elsewhere herein can be modified using a CRISPR-Cas and/or Cas-based system.

In general, a CRISPR-Cas or CRISPR system as used in herein and in documents, such as International Patent Publication No. WO 2014/093622 (PCT/US2013/074667), refers collectively to transcripts and other elements involved in the expression of or directing the activity of CRISPR-associated (“Cas”) genes, including sequences encoding a Cas gene, a tracr (trans-activating CRISPR) sequence (e.g. tracrRNA or an active partial tracrRNA), a tracr-mate sequence (encompassing a “direct repeat” and a tracrRNA-processed partial direct repeat in the context of an endogenous CRISPR system), a guide sequence (also referred to as a “spacer” in the context of an endogenous CRISPR system), or “RNA(s)” as that term is herein used (e.g., RNA(s) to guide Cas, such as Cas9, e.g. CRISPR RNA and transactivating (tracr) RNA or a single guide RNA (sgRNA) (chimeric RNA)) or other sequences and transcripts from a CRISPR locus. In general, a CRISPR system is characterized by elements that promote the formation of a CRISPR complex at the site of a target sequence (also referred to as a protospacer in the context of an endogenous CRISPR system). See, e.g, Shmakov et al. (2015) “Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems”, Molecular Cell, DOI: dx.doi.org/10.1016/j.molcel.2015.10.008.

CRISPR-Cas systems can generally fall into two classes based on their architectures of their effector molecules, which are each further subdivided by type and subtype. The two class are Class 1 and Class 2. Class 1 CRISPR-Cas systems have effector modules composed of multiple Cas proteins, some of which form crRNA-binding complexes, while Class 2 CRISPR-Cas systems include a single, multi-domain crRNA-binding protein.

In some embodiments, the CRISPR-Cas system that can be used to modify a polynucleotide of the present invention described herein can be a Class 1 CRISPR-Cas system. In some embodiments, the CRISPR-Cas system that can be used to modify a polynucleotide of the present invention described herein can be a Class 2 CRISPR-Cas system.

Class 1 CRISPR-Cas Systems

In some embodiments, the CRISPR-Cas system that can be used to modify a polynucleotide of the present invention described herein can be a Class 1 CRISPR-Cas system. Class 1 CRISPR-Cas systems are divided into types I, II, and IV. Makarova et al. 2020. Nat. Rev. 18: 67-83., particularly as described in FIG. 1. Type I CRISPR-Cas systems are divided into 9 subtypes (I-A, I-B, I-C, I-D, I-E, I-F1, I-F2, I-F3, and IG). Makarova et al., 2020. Class 1, Type I CRISPR-Cas systems can contain a Cas3 protein that can have helicase activity. Type III CRISPR-Cas systems are divided into 6 subtypes (III-A, III-B, III-E, and III-F). Type III CRISPR-Cas systems can contain a Cas10 that can include an RNA recognition motif called Palm and a cyclase domain that can cleave polynucleotides. Makarova et al., 2020. Type IV CRISPR-Cas systems are divided into 3 subtypes. (IV-A, IV-B, and IV-C). Makarova et al., 2020. Class 1 systems also include CRISPR-Cas variants, including Type I-A, I-B, I-E, I-F and I-U variants, which can include variants carried by transposons and plasmids, including versions of subtype I-F encoded by a large family of Tn7-like transposon and smaller groups of Tn7-like transposons that encode similarly degraded subtype I-B systems. Peters et al., PNAS 114 (35) (2017); DOI: 10.1073/pnas.1709035114; see also, Makarova et al. 2018. The CRISPR Journal, v. 1, n5, FIG. 5.

The Class 1 systems typically use a multi-protein effector complex, which can, in some embodiments, include ancillary proteins, such as one or more proteins in a complex referred to as a CRISPR-associated complex for antiviral defense (Cascade), one or more adaptation proteins (e.g., Cas1, Cas2, RNA nuclease), and/or one or more accessory proteins (e.g., Cas 4, DNA nuclease), CRISPR associated Rossman fold (CARF) domain containing proteins, and/or RNA transcriptase.

The backbone of the Class 1 CRISPR-Cas system effector complexes can be formed by RNA recognition motif domain-containing protein(s) of the repeat-associated mysterious proteins (RAMPs) family subunits (e.g., Cas 5, Cas6, and/or Cas7). RAMP proteins are characterized by having one or more RNA recognition motif domains. In some embodiments, multiple copies of RAMPs can be present. In some embodiments, the Class I CRISPR-Cas system can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more Cas5, Cas6, and/or Cas 7 proteins. In some embodiments, the Cas6 protein is an RNAse, which can be responsible for pre-crRNA processing. When present in a Class 1 CRISPR-Cas system, Cas6 can be optionally physically associated with the effector complex.

Class 1 CRISPR-Cas system effector complexes can, in some embodiments, also include a large subunit. The large subunit can be composed of or include a Cas8 and/or Cas10 protein. See, e.g., FIGS. 1 and 2. Koonin E V, Makarova K S. 2019. Phil. Trans. R. Soc. B 374: 20180087, DOI: 10.1098/rstb.2018.0087 and Makarova et al. 2020.

Class 1 CRISPR-Cas system effector complexes can, in some embodiments, include a small subunit (for example, Cash 1). See, e.g., FIGS. 1 and 2. Koonin E V, Makarova K S. 2019 Origins and Evolution of CRISPR-Cas systems. Phil. Trans. R. Soc. B 374: 20180087, DOI: 10.1098/rstb.2018.0087.

In some embodiments, the Class 1 CRISPR-Cas system can be a Type I CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-A CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-B CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-C CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-D CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-E CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-F1 CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-F2 CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-F3 CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a subtype I-G CRISPR-Cas system. In some embodiments, the Type I CRISPR-Cas system can be a CRISPR Cas variant, such as a Type I-A, I-B, I-E, I-F and I-U variants, which can include variants carried by transposons and plasmids, including versions of subtype I-F encoded by a large family of Tn7-like transposon and smaller groups of Tn7-like transposons that encode similarly degraded subtype I-B systems as previously described.

In some embodiments, the Class 1 CRISPR-Cas system can be a Type III CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-A CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-B CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-C CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-D CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-E CRISPR-Cas system. In some embodiments, the Type III CRISPR-Cas system can be a subtype III-F CRISPR-Cas system.

In some embodiments, the Class 1 CRISPR-Cas system can be a Type IV CRISPR-Cas-system. In some embodiments, the Type IV CRISPR-Cas system can be a subtype IV-A CRISPR-Cas system. In some embodiments, the Type IV CRISPR-Cas system can be a subtype IV-B CRISPR-Cas system. In some embodiments, the Type IV CRISPR-Cas system can be a subtype IV-C CRISPR-Cas system.

The effector complex of a Class 1 CRISPR-Cas system can, in some embodiments, include a Cas3 protein that is optionally fused to a Cas2 protein, a Cas4, a Cas5, a Cash, a Cas7, a Cas8, a Cas10, a Cas11, or a combination thereof. In some embodiments, the effector complex of a Class 1 CRISPR-Cas system can have multiple copies, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14, of any one or more Cas proteins.

Class 2 CRISPR-Cas Systems

The compositions, systems, and methods described in greater detail elsewhere herein can be designed and adapted for use with Class 2 CRISPR-Cas systems. Thus, in some embodiments, the CRISPR-Cas system is a Class 2 CRISPR-Cas system. Class 2 systems are distinguished from Class 1 systems in that they have a single, large, multi-domain effector protein. In certain example embodiments, the Class 2 system can be a Type II, Type V, or Type VI system, which are described in Makarova et al. “Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants” Nature Reviews Microbiology, 18:67-81 (February 2020), incorporated herein by reference. Each type of Class 2 system is further divided into subtypes. See Markova et al. 2020, particularly at Figure. 2. Class 2, Type II systems can be divided into 4 subtypes: II-A, II-B, II-C1, and II-C2. Class 2, Type V systems can be divided into 17 subtypes: V-A, V-B1, V-B2, V-C, V-D, V-E, V-F1, V-F1(V-U3), V-F2, V-F3, V-G, V-H, V-I, V-K (V-U5), V-U1, V-U2, and V-U4. Class 2, Type IV systems can be divided into 5 subtypes: VI-A, VI-B1, VI-B2, VI-C, and VI-D.

The distinguishing feature of these types is that their effector complexes consist of a single, large, multi-domain protein. Type V systems differ from Type II effectors (e.g., Cas9), which contain two nuclear domains that are each responsible for the cleavage of one strand of the target DNA, with the HNH nuclease inserted inside the Ruv-C like nuclease domain sequence. The Type V systems (e.g., Cas12) only contain a RuvC-like nuclease domain that cleaves both strands. Type VI (Cas13) are unrelated to the effectors of Type II and V systems and contain two HEPN domains and target RNA. Cas13 proteins also display collateral activity that is triggered by target recognition. Some Type V systems have also been found to possess this collateral activity with two single-stranded DNA in in vitro contexts.

In some embodiments, the Class 2 system is a Type II system. In some embodiments, the Type II CRISPR-Cas system is a II-A CRISPR-Cas system. In some embodiments, the Type II CRISPR-Cas system is a II-B CRISPR-Cas system. In some embodiments, the Type II CRISPR-Cas system is a II-C1 CRISPR-Cas system. In some embodiments, the Type II CRISPR-Cas system is a II-C2 CRISPR-Cas system. In some embodiments, the Type II system is a Cas9 system. In some embodiments, the Type II system includes a Cas9.

In some embodiments, the Class 2 system is a Type V system. In some embodiments, the Type V CRISPR-Cas system is a V-A CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-B1 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-B2 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-C CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-D CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-E CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-F1 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-F1 (V-U3) CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-F2 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-F3 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-G CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-H CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-I CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-K (V-U5) CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-U1 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-U2 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system is a V-U4 CRISPR-Cas system. In some embodiments, the Type V CRISPR-Cas system includes a Cas12a (Cpf1), Cas12b (C2c1), Cas12c (C2c3), CasX, and/or Cas14.

In some embodiments the Class 2 system is a Type VI system. In some embodiments, the Type VI CRISPR-Cas system is a VI-A CRISPR-Cas system. In some embodiments, the Type VI CRISPR-Cas system is a VI-B1 CRISPR-Cas system. In some embodiments, the Type VI CRISPR-Cas system is a VI-B2 CRISPR-Cas system. In some embodiments, the Type VI CRISPR-Cas system is a VI-C CRISPR-Cas system. In some embodiments, the Type VI CRISPR-Cas system is a VI-D CRISPR-Cas system. In some embodiments, the Type VI CRISPR-Cas system includes a Cas13a (C2c2), Cas13b (Group 29/30), Cas13c, and/or Cas13d.

Specialized Cas-Based Systems

In some embodiments, the system is a Cas-based system that is capable of performing a specialized function or activity. For example, the Cas protein may be fused, operably coupled to, or otherwise associated with one or more functionals domains. In certain example embodiments, the Cas protein may be a catalytically dead Cas protein (“dCas”) and/or have nickase activity. A nickase is a Cas protein that cuts only one strand of a double stranded target. In such embodiments, the dCas or nickase provide a sequence specific targeting functionality that delivers the functional domain to or proximate a target sequence. Example functional domains that may be fused to, operably coupled to, or otherwise associated with a Cas protein can be or include, but are not limited to a nuclear localization signal (NLS) domain, a nuclear export signal (NES) domain, a translational activation domain, a transcriptional activation domain (e.g. VP64, p65, MyoD1, HSF1, RTA, and SETT/9), a translation initiation domain, a transcriptional repression domain (e.g., a KRAB domain, NuE domain, NcoR domain, and a SID domain such as a SID4X domain), a nuclease domain (e.g., Fold), a histone modification domain (e.g., a histone acetyltransferase), a light inducible/controllable domain, a chemically inducible/controllable domain, a transposase domain, a homologous recombination machinery domain, a recombinase domain, an integrase domain, and combinations thereof. Methods for generating catalytically dead Cas9 or a nickase Cas9 (WO 2014/204725, Ran et al. Cell. 2013 Sep. 12; 154(6):1380-1389), Cas12 (Liu et al. Nature Communications, 8, 2095 (2017), and Cas13 (WO 2019/005884, WO2019/060746) are known in the art and incorporated herein by reference.

In some embodiments, the functional domains can have one or more of the following activities: methylase activity, demethylase activity, translation activation activity, translation initiation activity, translation repression activity, transcription activation activity, transcription repression activity, transcription release factor activity, histone modification activity, nuclease activity, single-strand RNA cleavage activity, double-strand RNA cleavage activity, single-strand DNA cleavage activity, double-strand DNA cleavage activity, molecular switch activity, chemical inducibility, light inducibility, and nucleic acid binding activity. In some embodiments, the one or more functional domains may comprise epitope tags or reporters. Non-limiting examples of epitope tags include histidine (His) tags, V5 tags, FLAG tags, influenza hemagglutinin (HA) tags, Myc tags, VSV-G tags, and thioredoxin (Trx) tags. Examples of reporters include, but are not limited to, glutathione-S-transferase (GST), horseradish peroxidase (HRP), chloramphenicol acetyltransferase (CAT) beta-galactosidase, beta-glucuronidase, luciferase, green fluorescent protein (GFP), HcRed, DsRed, cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and auto-fluorescent proteins including blue fluorescent protein (BFP).

The one or more functional domain(s) may be positioned at, near, and/or in proximity to a terminus of the effector protein (e.g., a Cas protein). In embodiments having two or more functional domains, each of the two can be positioned at or near or in proximity to a terminus of the effector protein (e.g., a Cas protein). In some embodiments, such as those where the functional domain is operably coupled to the effector protein, the one or more functional domains can be tethered or linked via a suitable linker (including, but not limited to, GlySer linkers) to the effector protein (e.g., a Cas protein). When there is more than one functional domain, the functional domains can be same or different. In some embodiments, all the functional domains are the same. In some embodiments, all of the functional domains are different from each other. In some embodiments, at least two of the functional domains are different from each other. In some embodiments, at least two of the functional domains are the same as each other.

Other suitable functional domains can be found, for example, in International Application Publication No. WO 2019/018423.

Split CRISPR-Cas Systems

In some embodiments, the CRISPR-Cas system is a split CRISPR-Cas system. See e.g., Zetche et al., 2015. Nat. Biotechnol. 33(2): 139-142 and WO 2019/018423, the compositions and techniques of which can be used in and/or adapted for use with the present invention. Split CRISPR-Cas proteins are set forth herein and in documents incorporated herein by reference in further detail herein. In certain embodiments, each part of a split CRISPR protein are attached to a member of a specific binding pair, and when bound with each other, the members of the specific binding pair maintain the parts of the CRISPR protein in proximity. In certain embodiments, each part of a split CRISPR protein is associated with an inducible binding pair. An inducible binding pair is one which is capable of being switched “on” or “off” by a protein or small molecule that binds to both members of the inducible binding pair. In some embodiments, CRISPR proteins may preferably split between domains, leaving domains intact. In particular embodiments, said Cas split domains (e.g., RuvC and HNH domains in the case of Cas9) can be simultaneously or sequentially introduced into the cell such that said split Cas domain(s) process the target nucleic acid sequence in the algae cell. The reduced size of the split Cas compared to the wild type Cas allows other methods of delivery of the systems to the cells, such as the use of cell penetrating peptides as described herein.

DNA and RNA Base Editing

In some embodiments, a polynucleotide of the present invention described elsewhere herein can be modified using a base editing system. In some embodiments, a Cas protein is connected or fused to a nucleotide deaminase. Thus, in some embodiments the Cas-based system can be a base editing system. As used herein “base editing” refers generally to the process of polynucleotide modification via a CRISPR-Cas-based or Cas-based system that does not include excising nucleotides to make the modification. Base editing can convert base pairs at precise locations without generating excess undesired editing byproducts that can be made using traditional CRISPR-Cas systems.

In certain example embodiments, the nucleotide deaminase may be a DNA base editor used in combination with a DNA binding Cas protein such as, but not limited to, Class 2 Type II and Type V systems. Two classes of DNA base editors are generally known: cytosine base editors (CBEs) and adenine base editors (ABEs). CBEs convert a C•G base pair into a T•A base pair (Komor et al. 2016. Nature. 533:420-424; Nishida et al. 2016. Science. 353; and Li et al. Nat. Biotech. 36:324-327) and ABEs convert an A•T base pair to a G•C base pair. Collectively, CBEs and ABEs can mediate all four possible transition mutations (C to T, A to G, T to C, and G to A). Rees and Liu. 2018. Nat. Rev. Genet. 19(12): 770-788, particularly at FIGS. 1b, 2a-2c, 3a-3f, and Table 1. In some embodiments, the base editing system includes a CBE and/or an ABE. In some embodiments, a polynucleotide of the present invention described elsewhere herein can be modified using a base editing system. Rees and Liu. 2018. Nat. Rev. Gent. 19(12):770-788. Base editors also generally do not need a DNA donor template and/or rely on homology-directed repair. Komor et al. 2016. Nature. 533:420-424; Nishida et al. 2016. Science. 353; and Gaudeli et al. 2017. Nature. 551:464-471. Upon binding to a target locus in the DNA, base pairing between the guide RNA of the system and the target DNA strand leads to displacement of a small segment of ssDNA in an “R-loop”. Nishimasu et al. Cell. 156:935-949. DNA bases within the ssDNA bubble are modified by the enzyme component, such as a deaminase. In some systems, the catalytically disabled Cas protein can be a variant or modified Cas can have nickase functionality and can generate a nick in the non-edited DNA strand to induce cells to repair the non-edited strand using the edited strand as a template. Komor et al. 2016. Nature. 533:420-424; Nishida et al. 2016. Science. 353; and Gaudeli et al. 2017. Nature. 551:464-471.

Other Example Type V base editing systems are described in WO 2018/213708, WO 2018/213726, PCT/US2018/067207, PCT/US2018/067225, and PCT/US2018/067307 which are incorporated by referenced herein.

In certain example embodiments, the base editing system may be a RNA base editing system. As with DNA base editors, a nucleotide deaminase capable of converting nucleotide bases may be fused to a Cas protein. However, in these embodiments, the Cas protein will need to be capable of binding RNA. Example RNA binding Cas proteins include, but are not limited to, RNA-binding Cas9s such as Francisella novicida Cas9 (“FnCas9”), and Class 2 Type VI Cas systems. The nucleotide deaminase may be a cytidine deaminase or an adenosine deaminase, or an adenosine deaminase engineered to have cytidine deaminase activity. In certain example embodiments, the RNA based editor may be used to delete or introduce a post-translation modification site in the expressed mRNA. In contrast to DNA base editors, whose edits are permanent in the modified cell, RNA base editors can provide edits where finer temporal control may be needed, for example in modulating a particular immune response. Example Type VI RNA-base editing systems are described in Cox et al. 2017. Science 358: 1019-1027, WO 2019/005884, WO 2019/005886, WO 2019/071048, PCT/US20018/05179, PCT/US2018/067207, which are incorporated herein by reference. An example FnCas9 system that may be adapted for RNA base editing purposes is described in WO 2016/106236, which is incorporated herein by reference.

An example method for delivery of base-editing systems, including use of a split-intein approach to divide CBE and ABE into reconstituble halves, is described in Levy et al. Nature Biomedical Engineering doi.org/10.1038/s41441-019-0505-5 (2019), which is incorporated herein by reference.

Prime Editors

In some embodiments, a polynucleotide of the present invention described elsewhere herein can be modified using a prime editing system See e.g. Anzalone et al. 2019. Nature. 576: 149-157. Like base editing systems, prime editing systems can be capable of targeted modification of a polynucleotide without generating double stranded breaks and does not require donor templates. Further prime editing systems can be capable of all 12 possible combination swaps. Prime editing can operate via a “search-and-replace” methodology and can mediate targeted insertions, deletions, all 12 possible base-to-base conversion, and combinations thereof. Generally, a prime editing system, as exemplified by PE1, PE2, and PE3 (Id.), can include a reverse transcriptase fused or otherwise coupled or associated with an RNA-programmable nickase, and a prime-editing extended guide RNA (pegRNA) to facility direct copying of genetic information from the extension on the pegRNA into the target polynucleotide. Embodiments that can be used with the present invention include these and variants thereof. Prime editing can have the advantage of lower off-target activity than traditional CRIPSR-Cas systems along with few byproducts and greater or similar efficiency as compared to traditional CRISPR-Cas systems.

In some embodiments, the prime editing guide molecule can specify both the target polynucleotide information (e.g. sequence) and contain a new polynucleotide cargo that replaces target polynucleotides. To initiate transfer from the guide molecule to the target polynucleotide, the PE system can nick the target polynucleotide at a target side to expose a 3′hydroxyl group, which can prime reverse transcription of an edit-encoding extension region of the guide molecule (e.g. a prime editing guide molecule or peg guide molecule) directly into the target site in the target polynucleotide. See e.g. Anzalone et al. 2019. Nature. 576: 149-157, particularly at FIGS. 1b, 1c, related discussion, and Supplementary discussion.

In some embodiments, a prime editing system can be composed of a Cas polypeptide having nickase activity, a reverse transcriptase, and a guide molecule. The Cas polypeptide can lack nuclease activity. The guide molecule can include a target binding sequence as well as a primer binding sequence and a template containing the edited polynucleotide sequence. The guide molecule, Cas polypeptide, and/or reverse transcriptase can be coupled together or otherwise associate with each other to form an effector complex and edit a target sequence. In some embodiments, the Cas polypeptide is a Class 2, Type V Cas polypeptide. In some embodiments, the Cas polypeptide is a Cas9 polypeptide (e.g. is a Cas9 nickase). In some embodiments, the Cas polypeptide is fused to the reverse transcriptase. In some embodiments, the Cas polypeptide is linked to the reverse transcriptase.

In some embodiments, the prime editing system can be a PE1 system or variant thereof, a PE2 system or variant thereof, or a PE3 (e.g. PE3, PE3b) system. See e.g., Anzalone et al. 2019. Nature. 576: 149-157, particularly at pgs. 2-3, FIGS. 2a, 3a-3f, 4a-4b, Extended data FIGS. 3a-3b, 4,

The peg guide molecule can be about 10 to about 200 or more nucleotides in length, such as 10 to/or 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, or 200 or more nucleotides in length. Optimization of the peg guide molecule can be accomplished as described in Anzalone et al. 2019. Nature. 576: 149-157, particularly at pg. 3, FIG. 2a-2b, and Extended Data FIGS. 5a-c.

CRISPR Associated Transposase (CAST) Systems

In some embodiments, a polynucleotide of the present invention described elsewhere herein can be modified using a CRISPR Associated Transposase (“CAST”) system. CAST system can include a Cas protein that is catalytically inactive, or engineered to be catalytically active, and further comprises a transposase (or subunits thereof) that catalyze RNA-guided DNA transposition. Such systems are able to insert DNA sequences at a target site in a DNA molecule without relying on host cell repair machinery. CAST systems can be Class1 or Class 2 CAST systems. An example Class 1 system is described in Klompe et al. Nature, doi:10.1038/s41586-019-1323, which is in incorporated herein by reference. An example Class 2 system is described in Strecker et al. Science. 10/1126/science. aax9181 (2019), and PCT/US2019/066835 which are incorporated herein by reference.

Guide Molecules

The CRISPR-Cas or Cas-Based system described herein can, in some embodiments, include one or more guide molecules. The terms guide molecule, guide sequence and guide polynucleotide, refer to polynucleotides capable of guiding Cas to a target genomic locus and are used interchangeably as in foregoing cited documents such as WO 2014/093622 (PCT/US2013/074667). In general, a guide sequence is any polynucleotide sequence having sufficient complementarity with a target polynucleotide sequence to hybridize with the target sequence and direct sequence-specific binding of a CRISPR complex to the target sequence. The guide molecule can be a polynucleotide.

The ability of a guide sequence (within a nucleic acid-targeting guide RNA) to direct sequence-specific binding of a nucleic acid-targeting complex to a target nucleic acid sequence may be assessed by any suitable assay. For example, the components of a nucleic acid-targeting CRISPR system sufficient to form a nucleic acid-targeting complex, including the guide sequence to be tested, may be provided to a host cell having the corresponding target nucleic acid sequence, such as by transfection with vectors encoding the components of the nucleic acid-targeting complex, followed by an assessment of preferential targeting (e.g., cleavage) within the target nucleic acid sequence, such as by Surveyor assay (Qui et al. 2004. BioTechniques. 36(4)702-707). Similarly, cleavage of a target nucleic acid sequence may be evaluated in a test tube by providing the target nucleic acid sequence, components of a nucleic acid-targeting complex, including the guide sequence to be tested and a control guide sequence different from the test guide sequence, and comparing binding or rate of cleavage at the target sequence between the test and control guide sequence reactions. Other assays are possible and will occur to those skilled in the art.

In some embodiments, the guide molecule is an RNA. The guide molecule(s) (also referred to interchangeably herein as guide polynucleotide and guide sequence) that are included in the CRISPR-Cas or Cas based system can be any polynucleotide sequence having sufficient complementarity with a target nucleic acid sequence to hybridize with the target nucleic acid sequence and direct sequence-specific binding of a nucleic acid-targeting complex to the target nucleic acid sequence. In some embodiments, the degree of complementarity, when optimally aligned using a suitable alignment algorithm, can be about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, or more. Optimal alignment may be determined with the use of any suitable algorithm for aligning sequences, non-limiting examples of which include the Smith-Waterman algorithm, the Needleman-Wunsch algorithm, algorithms based on the Burrows-Wheeler Transform (e.g., the Burrows Wheeler Aligner), ClustalW, Clustal X, BLAT, Novoalign (Novocraft Technologies; available at www.novocraft.com), ELAND (Illumina, San Diego, Calif.), SOAP (available at soap.genomics.org.cn), and Maq (available at maq.sourceforge.net).

A guide sequence, and hence a nucleic acid-targeting guide may be selected to target any target nucleic acid sequence. The target sequence may be DNA. The target sequence may be any RNA sequence. In some embodiments, the target sequence may be a sequence within an RNA molecule selected from the group consisting of messenger RNA (mRNA), pre-mRNA, ribosomal RNA (rRNA), transfer RNA (tRNA), micro-RNA (miRNA), small interfering RNA (siRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), double stranded RNA (dsRNA), non-coding RNA (ncRNA), long non-coding RNA (lncRNA), and small cytoplasmatic RNA (scRNA). In some preferred embodiments, the target sequence may be a sequence within an RNA molecule selected from the group consisting of mRNA, pre-mRNA, and rRNA. In some preferred embodiments, the target sequence may be a sequence within an RNA molecule selected from the group consisting of ncRNA, and lncRNA. In some more preferred embodiments, the target sequence may be a sequence within an mRNA molecule or a pre-mRNA molecule.

In some embodiments, a nucleic acid-targeting guide is selected to reduce the degree secondary structure within the nucleic acid-targeting guide. In some embodiments, about or less than about 75%, 50%, 40%, 30%, 25%, 20%, 15%, 10%, 5%, 1%, or fewer of the nucleotides of the nucleic acid-targeting guide participate in self-complementary base pairing when optimally folded. Optimal folding may be determined by any suitable polynucleotide folding algorithm. Some programs are based on calculating the minimal Gibbs free energy. An example of one such algorithm is mFold, as described by Zuker and Stiegler (Nucleic Acids Res. 9 (1981), 133-148). Another example folding algorithm is the online webserver RNAfold, developed at Institute for Theoretical Chemistry at the University of Vienna, using the centroid structure prediction algorithm (see e.g., A. R. Gruber et al., 2008, Cell 106(1): 23-24; and P A Carr and G M Church, 2009, Nature Biotechnology 27(12): 1151-62).

In certain embodiments, a guide RNA or crRNA may comprise, consist essentially of, or consist of a direct repeat (DR) sequence and a guide sequence or spacer sequence. In certain embodiments, the guide RNA or crRNA may comprise, consist essentially of, or consist of a direct repeat sequence fused or linked to a guide sequence or spacer sequence. In certain embodiments, the direct repeat sequence may be located upstream (i.e., 5′) from the guide sequence or spacer sequence. In other embodiments, the direct repeat sequence may be located downstream (i.e., 3′) from the guide sequence or spacer sequence.

In certain embodiments, the crRNA comprises a stem loop, preferably a single stem loop. In certain embodiments, the direct repeat sequence forms a stem loop, preferably a single stem loop.

In certain embodiments, the spacer length of the guide RNA is from 15 to 35 nt. In certain embodiments, the spacer length of the guide RNA is at least 15 nucleotides. In certain embodiments, the spacer length is from 15 to 17 nt, e.g., 15, 16, or 17 nt, from 17 to 20 nt, e.g., 17, 18, 19, or 20 nt, from 20 to 24 nt, e.g., 20, 21, 22, 23, or 24 nt, from 23 to 25 nt, e.g., 23, 24, or 25 nt, from 24 to 27 nt, e.g., 24, 25, 26, or 27 nt, from 27 to 30 nt, e.g., 27, 28, 29, or 30 nt, from 30 to 35 nt, e.g., 30, 31, 32, 33, 34, or 35 nt, or 35 nt or longer.

The “tracrRNA” sequence or analogous terms includes any polynucleotide sequence that has sufficient complementarity with a crRNA sequence to hybridize. In some embodiments, the degree of complementarity between the tracrRNA sequence and crRNA sequence along the length of the shorter of the two when optimally aligned is about or more than about 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99%, or higher. In some embodiments, the tracr sequence is about or more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, 50, or more nucleotides in length. In some embodiments, the tracr sequence and crRNA sequence are contained within a single transcript, such that hybridization between the two produces a transcript having a secondary structure, such as a hairpin.

In general, degree of complementarity is with reference to the optimal alignment of the sca sequence and tracr sequence, along the length of the shorter of the two sequences. Optimal alignment may be determined by any suitable alignment algorithm, and may further account for secondary structures, such as self-complementarity within either the sca sequence or tracr sequence. In some embodiments, the degree of complementarity between the tracr sequence and sca sequence along the length of the shorter of the two when optimally aligned is about or more than about 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99%, or higher.

In some embodiments, the degree of complementarity between a guide sequence and its corresponding target sequence can be about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, or 100%; a guide or RNA or sgRNA can be about or more than about 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or more nucleotides in length; or guide or RNA or sgRNA can be less than about 75, 50, 45, 40, 35, 30, 25, 20, 15, 12, or fewer nucleotides in length; and tracr RNA can be 30 or 50 nucleotides in length. In some embodiments, the degree of complementarity between a guide sequence and its corresponding target sequence is greater than 94.5% or 95% or 95.5% or 96% or 96.5% or 97% or 97.5% or 98% or 98.5% or 99% or 99.5% or 99.9%, or 100%. Off target is less than 100% or 99.9% or 99.5% or 99% or 99% or 98.5% or 98% or 97.5% or 97% or 96.5% or 96% or 95.5% or 95% or 94.5% or 94% or 93% or 92% or 91% or 90% or 89% or 88% or 87% or 86% or 85% or 84% or 83% or 82% or 81% or 80% complementarity between the sequence and the guide, with it advantageous that off target is 100% or 99.9% or 99.5% or 99% or 99% or 98.5% or 98% or 97.5% or 97% or 96.5% or 96% or 95.5% or 95% or 94.5% complementarity between the sequence and the guide.

In some embodiments according to the invention, the guide RNA (capable of guiding Cas to a target locus) may comprise (1) a guide sequence capable of hybridizing to a genomic target locus in the eukaryotic cell; (2) a tracr sequence; and (3) a tracr mate sequence. All (1) to (3) may reside in a single RNA, i.e., an sgRNA (arranged in a 5′ to 3′ orientation), or the tracr RNA may be a different RNA than the RNA containing the guide and tracr sequence. The tracr hybridizes to the tracr mate sequence and directs the CRISPR/Cas complex to the target sequence. Where the tracr RNA is on a different RNA than the RNA containing the guide and tracr sequence, the length of each RNA may be optimized to be shortened from their respective native lengths, and each may be independently chemically modified to protect from degradation by cellular RNase or otherwise increase stability.

Many modifications to guide sequences are known in the art and are further contemplated within the context of this invention. Various modifications may be used to increase the specificity of binding to the target sequence and/or increase the activity of the Cas protein and/or reduce off-target effects. Example guide sequence modifications are described in PCT US2019/045582, specifically paragraphs [0178]-[0333]. which is incorporated herein by reference.

Target Sequences, PAMs, and PFSs
Target Sequences

In the context of formation of a CRISPR complex, “target sequence” refers to a sequence to which a guide sequence is designed to have complementarity, where hybridization between a target sequence and a guide sequence promotes the formation of a CRISPR complex. A target sequence may comprise RNA polynucleotides. The term “target RNA” refers to an RNA polynucleotide being or comprising the target sequence. In other words, the target polynucleotide can be a polynucleotide or a part of a polynucleotide to which a part of the guide sequence is designed to have complementarity with and to which the effector function mediated by the complex comprising the CRISPR effector protein and a guide molecule is to be directed. In some embodiments, a target sequence is located in the nucleus or cytoplasm of a cell.

The guide sequence can specifically bind a target sequence in a target polynucleotide. The target polynucleotide may be DNA. The target polynucleotide may be RNA. The target polynucleotide can have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. or more) target sequences. The target polynucleotide can be on a vector. The target polynucleotide can be genomic DNA. The target polynucleotide can be episomal. Other forms of the target polynucleotide are described elsewhere herein.

The target sequence may be DNA. The target sequence may be any RNA sequence. In some embodiments, the target sequence may be a sequence within an RNA molecule selected from the group consisting of messenger RNA (mRNA), pre-mRNA, ribosomal RNA (rRNA), transfer RNA (tRNA), micro-RNA (miRNA), small interfering RNA (siRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), double stranded RNA (dsRNA), non-coding RNA (ncRNA), long non-coding RNA (lncRNA), and small cytoplasmatic RNA (scRNA). In some preferred embodiments, the target sequence (also referred to herein as a target polynucleotide) may be a sequence within an RNA molecule selected from the group consisting of mRNA, pre-mRNA, and rRNA. In some preferred embodiments, the target sequence may be a sequence within an RNA molecule selected from the group consisting of ncRNA, and lncRNA. In some more preferred embodiments, the target sequence may be a sequence within an mRNA molecule or a pre-mRNA molecule.

PAM and PFS Elements

PAM elements are sequences that can be recognized and bound by Cas proteins. Cas proteins/effector complexes can then unwind the dsDNA at a position adjacent to the PAM element. It will be appreciated that Cas proteins and systems that include them that target RNA do not require PAM sequences (Marraffini et al. 2010. Nature. 463:568-571). Instead, many rely on PFSs, which are discussed elsewhere herein. In certain embodiments, the target sequence should be associated with a PAM (protospacer adjacent motif) or PFS (protospacer flanking sequence or site), that is, a short sequence recognized by the CRISPR complex. Depending on the nature of the CRISPR-Cas protein, the target sequence should be selected, such that its complementary sequence in the DNA duplex (also referred to herein as the non-target sequence) is upstream or downstream of the PAM. In the embodiments, the complementary sequence of the target sequence is downstream or 3′ of the PAM or upstream or 5′ of the PAM. The precise sequence and length requirements for the PAM differ depending on the Cas protein used, but PAMs are typically 2-5 base pair sequences adjacent the protospacer (that is, the target sequence). Examples of the natural PAM sequences for different Cas proteins are provided herein below and the skilled person will be able to identify further PAM sequences for use with a given Cas protein.

The ability to recognize different PAM sequences depends on the Cas polypeptide(s) included in the system. See e.g., Gleditzsch et al. 2019. RNA Biology. 16(4):504-517. Table 3 below (from Gleditzsch et al.) shows several Cas polypeptides and the PAM sequence they recognize.

TABLE 3

Example PAM Sequences

Cas Protein
PAM Sequence

SpCas9
NGG/NRG

SaCas9
NGRRT or NGRRN

NmeCas9
NNNNGATT

CjCas9
NNNNRYAC

StCas9
NNAGAAW

Cas12a (Cpf1) (including LbCpf1
TTTV

and AsCpf1)

Cas12b (C2c1)
TTT, TTA, and TTC

Cas12c (C2c3)
TA

Cas12d (CasY)
TA

Cas12e (CasX)
5′-TTCN-3′

In a preferred embodiment, the CRISPR effector protein may recognize a 3′ PAM. In certain embodiments, the CRISPR effector protein may recognize a 3′ PAM which is 5′H, wherein H is A, C or U.

Further, engineering of the PAM Interacting (PI) domain on the Cas protein may allow programing of PAM specificity, improve target site recognition fidelity, and increase the versatility of the CRISPR-Cas protein, for example as described for Cas9 in Kleinstiver B P et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015 Jul. 23; 523(7561):481-5. doi: 10.1038/nature14592. As further detailed herein, the skilled person will understand that Cas13 proteins may be modified analogously. Gao et al, “Engineered Cpf1 Enzymes with Altered PAM Specificities,” bioRxiv 091611; doi: http://dx.doi.org/10.1101/091611 (Dec. 4, 2016). Doench et al. created a pool of sgRNAs, tiling across all possible target sites of a panel of six endogenous mouse and three endogenous human genes and quantitatively assessed their ability to produce null alleles of their target gene by antibody staining and flow cytometry. The authors showed that optimization of the PAM improved activity and also provided an on-line tool for designing sgRNAs.

PAM sequences can be identified in a polynucleotide using an appropriate design tool, which are commercially available as well as online. Such freely available tools include, but are not limited to, CRISPRFinder and CRISPRTarget. Mojica et al. 2009. Microbiol. 155(Pt. 3):733-740; Atschul et al. 1990. J. Mol. Biol. 215:403-410; Biswass et al. 2013 RNA Biol. 10:817-827; and Grissa et al. 2007. Nucleic Acid Res. 35:W52-57. Experimental approaches to PAM identification can include, but are not limited to, plasmid depletion assays (Jiang et al. 2013. Nat. Biotechnol. 31:233-239; Esvelt et al. 2013. Nat. Methods. 10:1116-1121; Kleinstiver et al. 2015. Nature. 523:481-485), screened by a high-throughput in vivo model called PAM-SCNAR (Pattanayak et al. 2013. Nat. Biotechnol. 31:839-843 and Leenay et al. 2016. Mol. Cell. 16:253), and negative screening (Zetsche et al. 2015. Cell. 163:759-771).

As previously mentioned, CRISPR-Cas systems that target RNA do not typically rely on PAM sequences. Instead such systems typically recognize protospacer flanking sites (PFSs) instead of PAMs Thus, Type VI CRISPR-Cas systems typically recognize protospacer flanking sites (PFSs) instead of PAMs. PFSs represents an analogue to PAMs for RNA targets. Type VI CRISPR-Cas systems employ a Cas13. Some Cas13 proteins analyzed to date, such as Cas13a (C2c2) identified from Leptotrichia shahii (LShCAs13a) have a specific discrimination against G at the 3′ end of the target RNA. The presence of a C at the corresponding crRNA repeat site can indicate that nucleotide pairing at this position is rejected. However, some Cas13 proteins (e.g., LwaCAs13a and PspCas13b) do not seem to have a PFS preference. See e.g., Gleditzsch et al. 2019. RNA Biology. 16(4):504-517.

Some Type VI proteins, such as subtype B, have 5′-recognition of D (G, T, A) and a 3′-motif requirement of NAN or NNA. One example is the Cas13b protein identified in Bergeyella zoohelcum (BzCas13b). See e.g., Gleditzsch et al. 2019. RNA Biology. 16(4):504-517.

Overall Type VI CRISPR-Cas systems appear to have less restrictive rules for substrate (e.g., target sequence) recognition than those that target DNA (e.g., Type V and type II).

Zinc Finger Nucleases

In some embodiments, the target polynucleotide is modified using a Zinc Finger nuclease or system thereof. One type of programmable DNA-binding domain is provided by artificial zinc-finger (ZF) technology, which involves arrays of ZF modules to target new DNA-binding sites in the genome. Each finger module in a ZF array targets three DNA bases. A customized array of individual zinc finger domains is assembled into a ZF protein (ZFP). ZFPs can comprise a functional domain. The first synthetic zinc finger nucleases (ZFNs) were developed by fusing a ZF protein to the catalytic domain of the Type IIS restriction enzyme FokI. (Kim, Y. G. et al., 1994, Chimeric restriction endonuclease, Proc. Natl. Acad. Sci. U.S.A. 91, 883-887; Kim, Y. G. et al., 1996, Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc. Natl. Acad. Sci. U.S.A. 93, 1156-1160). Increased cleavage specificity can be attained with decreased off target activity by use of paired ZFN heterodimers, each targeting different nucleotide sequences separated by a short spacer. (Doyon, Y. et al., 2011, Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat. Methods 8, 74-79). ZFPs can also be designed as transcription activators and repressors and have been used to target many genes in a wide variety of organisms. Exemplary methods of genome editing using ZFNs can be found for example in U.S. Pat. Nos. 6,534,261, 6,607,882, 6,746,838, 6,794,136, 6,824,978, 6,866,997, 6,933,113, 6,979,539, 7,013,219, 7,030,215, 7,220,719, 7,241,573, 7,241,574, 7,585,849, 7,595,376, 6,903,185, and 6,479,626, all of which are specifically incorporated by reference.

Sequences Related to Nucleus Targeting and Transportation

In some embodiments, one or more components (e.g., the Cas protein and/or deaminase) in the composition for engineering cells may comprise one or more sequences related to nucleus targeting and transportation. Such sequence may facilitate the one or more components in the composition for targeting a sequence within a cell. In order to improve targeting of the CRISPR-Cas protein and/or the nucleotide deaminase protein or catalytic domain thereof used in the methods of the present disclosure to the nucleus, it may be advantageous to provide one or both of these components with one or more nuclear localization sequences (NLSs).

In some embodiments, the NLSs used in the context of the present disclosure are heterologous to the proteins. Non-limiting examples of NLSs include an NLS sequence derived from: the NLS of the SV40 virus large T-antigen, having the amino acid sequence PKKKRKV (SEQ ID No. 3) or PKKKRKVEAS (SEQ ID No. 4); the NLS from nucleoplasmin (e.g., the nucleoplasmin bipartite NLS with the sequence KRPAATKKAGQAKKKK (SEQ ID No. 5)); the c-myc NLS having the amino acid sequence PAAKRVKLD (SEQ ID No. 6) or RQRRNELKRSP (SEQ ID No. 7); the hRNPA1 M9 NLS having the sequence NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY (SEQ ID No. 8); the sequence RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV (SEQ ID No. 9) of the IBB domain from importin-alpha; the sequences VSRKRPRP (SEQ ID No. 10) and PPKKARED (SEQ ID No. 11) of the myoma T protein; the sequence PQPKKKPL (SEQ ID No. 12) of human p53; the sequence SALIKKKKKMAP (SEQ ID No. 13) of mouse c-abl IV; the sequences DRLRR (SEQ ID No. 14) and PKQKKRK (SEQ ID No. 15) of the influenza virus NS1; the sequence RKLKKKIKKL (SEQ ID No. 16) of the Hepatitis virus delta antigen; the sequence REKKKFLKRR (SEQ ID No. 17) of the mouse Mx1 protein; the sequence KRKGDEVDGVDEVAKKKSKK (SEQ ID No. 18) of the human poly(ADP-ribose) polymerase; and the sequence RKCLQAGMNLEARKTKK (SEQ ID No. 19) of the steroid hormone receptors (human) glucocorticoid. In general, the one or more NLSs are of sufficient strength to drive accumulation of the DNA-targeting Cas protein in a detectable amount in the nucleus of a eukaryotic cell. In general, strength of nuclear localization activity may derive from the number of NLSs in the CRISPR-Cas protein, the particular NLS(s) used, or a combination of these factors. Detection of accumulation in the nucleus may be performed by any suitable technique. For example, a detectable marker may be fused to the nucleic acid-targeting protein, such that location within a cell may be visualized, such as in combination with a means for detecting the location of the nucleus (e.g., a stain specific for the nucleus such as DAPI). Cell nuclei may also be isolated from cells, the contents of which may then be analyzed by any suitable process for detecting protein, such as immunohistochemistry, Western blot, or enzyme activity assay. Accumulation in the nucleus may also be determined indirectly, such as by an assay for the effect of nucleic acid-targeting complex formation (e.g., assay for deaminase activity) at the target sequence, or assay for altered gene expression activity affected by DNA-targeting complex formation and/or DNA-targeting), as compared to a control not exposed to the CRISPR-Cas protein and deaminase protein, or exposed to a CRISPR-Cas and/or deaminase protein lacking the one or more NLSs.

The CRISPR-Cas and/or nucleotide deaminase proteins may be provided with 1 or more, such as with, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more heterologous NLSs. In some embodiments, the proteins comprises about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the amino-terminus, about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the carboxy-terminus, or a combination of these (e.g., zero or at least one or more NLS at the amino-terminus and zero or at one or more NLS at the carboxy terminus). When more than one NLS is present, each may be selected independently of the others, such that a single NLS may be present in more than one copy and/or in combination with one or more other NLSs present in one or more copies. In some embodiments, an NLS is considered near the N- or C-terminus when the nearest amino acid of the NLS is within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, or more amino acids along the polypeptide chain from the N- or C-terminus. In preferred embodiments of the CRISPR-Cas proteins, an NLS attached to the C-terminal of the protein.

In certain embodiments, the CRISPR-Cas protein and the deaminase protein are delivered to the cell or expressed within the cell as separate proteins. In these embodiments, each of the CRISPR-Cas and deaminase protein can be provided with one or more NLSs as described herein. In certain embodiments, the CRISPR-Cas and deaminase proteins are delivered to the cell or expressed with the cell as a fusion protein. In these embodiments one or both of the CRISPR-Cas and deaminase protein is provided with one or more NLSs. Where the nucleotide deaminase is fused to an adaptor protein (such as MS2) as described above, the one or more NLS can be provided on the adaptor protein, provided that this does not interfere with aptamer binding. In particular embodiments, the one or more NLS sequences may also function as linker sequences between the nucleotide deaminase and the CRISPR-Cas protein.

In certain embodiments, guides of the disclosure comprise specific binding sites (e.g. aptamers) for adapter proteins, which may be linked to or fused to an nucleotide deaminase or catalytic domain thereof. When such a guide forms a CRISPR complex (e.g., CRISPR-Cas protein binding to guide and target) the adapter proteins bind and, the nucleotide deaminase or catalytic domain thereof associated with the adapter protein is positioned in a spatial orientation which is advantageous for the attributed function to be effective.

The skilled person will understand that modifications to the guide which allow for binding of the adapter+nucleotide deaminase, but not proper positioning of the adapter+nucleotide deaminase (e.g. due to steric hindrance within the three dimensional structure of the CRISPR complex) are modifications which are not intended. The one or more modified guide may be modified at the tetra loop, the stem loop 1, stem loop 2, or stem loop 3, as described herein, preferably at either the tetra loop or stem loop 2, and in some cases at both the tetra loop and stem loop 2.

In some embodiments, a component (e.g., the dead Cas protein, the nucleotide deaminase protein or catalytic domain thereof, or a combination thereof) in the systems may comprise one or more nuclear export signals (NES), one or more nuclear localization signals (NLS), or any combinations thereof. In some cases, the NES may be an HIV Rev NES. In certain cases, the NES may be MAPK NES. When the component is a protein, the NES or NLS may be at the C terminus of component. Alternatively or additionally, the NES or NLS may be at the N terminus of component. In some examples, the Cas protein and optionally said nucleotide deaminase protein or catalytic domain thereof comprise one or more heterologous nuclear export signal(s) (NES(s)) or nuclear localization signal(s) (NLS(s)), preferably an HIV Rev NES or MAPK NES, preferably C-terminal.

Templates

In some embodiments, the composition for engineering cells comprise a template, e.g., a recombination template. A template may be a component of another vector as described herein, contained in a separate vector, or provided as a separate polynucleotide. In some embodiments, a recombination template is designed to serve as a template in homologous recombination, such as within or near a target sequence nicked or cleaved by a nucleic acid-targeting effector protein as a part of a nucleic acid-targeting complex.

In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.

The template sequence may undergo a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid may include sequence that corresponds to a site on the target sequence that is cleaved by a Cas protein mediated cleavage event. In an embodiment, the template nucleic acid may include sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas protein mediated event, and a second site on the target sequence that is cleaved in a second Cas protein mediated event.

In certain embodiments, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation. In certain embodiments, the template nucleic acid can include sequence which results in an alteration in a non-coding sequence, e.g., an alteration in an exon or in a 5′ or 3′ non-translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element.

A template nucleic acid having homology with a target position in a target gene may be used to alter the structure of a target sequence. The template sequence may be used to alter an unwanted structure, e.g., an unwanted or mutant nucleotide. The template nucleic acid may include sequence which, when integrated, results in: decreasing the activity of a positive control element; increasing the activity of a positive control element; decreasing the activity of a negative control element; increasing the activity of a negative control element; decreasing the expression of a gene; increasing the expression of a gene; increasing resistance to a disorder or disease; increasing resistance to viral entry; correcting a mutation or altering an unwanted amino acid residue conferring, increasing, abolishing or decreasing a biological property of a gene product, e.g., increasing the enzymatic activity of an enzyme, or increasing the ability of a gene product to interact with another molecule.

The template nucleic acid may include sequence which results in: a change in sequence of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more nucleotides of the target sequence.

A template polynucleotide may be of any suitable length, such as about or more than about 10, 15, 20, 25, 50, 75, 100, 150, 200, 500, 1000, or more nucleotides in length. In an embodiment, the template nucleic acid may be 20+/−10, 30+/−10, 40+/−10, 50+/−10, 60+/−10, 70+/−10, 80+/−10, 90+/−10, 100+/−10, 1 10+/−10, 120+/−10, 130+/−10, 140+/−10, 150+/−10, 160+/−10, 170+/−10, 1 80+/−10, 190+/−10, 200+/−10, 210+/−10, of 220+/−10 nucleotides in length. In an embodiment, the template nucleic acid may be 30+/−20, 40+/−20, 50+/−20, 60+/−20, 70+/−20, 80+/−20, 90+/−20, 100+/−20, 1 10+/−20, 120+/−20, 130+/−20, 140+/−20, I 50+/−20, 160+/−20, 170+/−20, 180+/−20, 190+/−20, 200+/−20, 210+/−20, of 220+/−20 nucleotides in length. In an embodiment, the template nucleic acid is 10 to 1,000, 20 to 900, 30 to 800, 40 to 700, 50 to 600, 50 to 500, 50 to 400, 50 to 300, 50 to 200, or 50 to 100 nucleotides in length.

In some embodiments, the template polynucleotide is complementary to a portion of a polynucleotide comprising the target sequence. When optimally aligned, a template polynucleotide might overlap with one or more nucleotides of a target sequences (e.g. about or more than about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100 or more nucleotides). In some embodiments, when a template sequence and a polynucleotide comprising a target sequence are optimally aligned, the nearest nucleotide of the template polynucleotide is within about 1, 5, 10, 15, 20, 25, 50, 75, 100, 200, 300, 400, 500, 1000, 5000, 10000, or more nucleotides from the target sequence.

The exogenous polynucleotide template comprises a sequence to be integrated (e.g., a mutated gene). The sequence for integration may be a sequence endogenous or exogenous to the cell. Examples of a sequence to be integrated include polynucleotides encoding a protein or a non-coding RNA (e.g., a microRNA). Thus, the sequence for integration may be operably linked to an appropriate control sequence or sequences. Alternatively, the sequence to be integrated may provide a regulatory function.

An upstream or downstream sequence may comprise from about 20 bp to about 2500 bp, for example, about 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, or 2500 bp. In some methods, the exemplary upstream or downstream sequence have about 200 bp to about 2000 bp, about 600 bp to about 1000 bp, or more particularly about 700 bp to about 1000.

In certain embodiments, one or both homology arms may be shortened to avoid including certain sequence repeat elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In some methods, the exogenous polynucleotide template may further comprise a marker. Such a marker may make it easy to screen for targeted integrations. Examples of suitable markers include restriction sites, fluorescent proteins, or selectable markers. The exogenous polynucleotide template of the disclosure can be constructed using recombinant techniques (see, for example, Sambrook et al., 2001 and Ausubel et al., 1996).

In certain embodiments, a template nucleic acid for correcting a mutation may designed for use as a single-stranded oligonucleotide. When using a single-stranded oligonucleotide, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length.

Suzuki et al. describe in vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration (2016, Nature 540:144-149).

TALE Nucleases

In some embodiments, a TALE nuclease or TALE nuclease system can be used to modify a target polynucleotide. In some embodiments, the methods provided herein use isolated, non-naturally occurring, recombinant or engineered DNA binding proteins that comprise TALE monomers or TALE monomers or half monomers as a part of their organizational structure that enable the targeting of nucleic acid sequences with improved efficiency and expanded specificity.

Naturally occurring TALEs or “wild type TALEs” are nucleic acid binding proteins secreted by numerous species of proteobacteria. TALE polypeptides contain a nucleic acid binding domain composed of tandem repeats of highly conserved monomer polypeptides that are predominantly 33, 34 or 35 amino acids in length and that differ from each other mainly in amino acid positions 12 and 13. In advantageous embodiments the nucleic acid is DNA. As used herein, the term “polypeptide monomers”, “TALE monomers” or “monomers” will be used to refer to the highly conserved repetitive polypeptide sequences within the TALE nucleic acid binding domain and the term “repeat variable di-residues” or “RVD” will be used to refer to the highly variable amino acids at positions 12 and 13 of the polypeptide monomers. As provided throughout the disclosure, the amino acid residues of the RVD are depicted using the IUPAC single letter code for amino acids. A general representation of a TALE monomer which is comprised within the DNA binding domain is X1-11-(X12X13)-X14-33 or 34 or 35, where the subscript indicates the amino acid position and X represents any amino acid. X12X13 indicate the RVDs. In some polypeptide monomers, the variable amino acid at position 13 is missing or absent and in such monomers, the RVD consists of a single amino acid. In such cases the RVD may be alternatively represented as X*, where X represents X12 and (*) indicates that X13 is absent. The DNA binding domain comprises several repeats of TALE monomers and this may be represented as (X1-11-(X12X13)-X14-33 or 34 or 35)z, where in an advantageous embodiment, z is at least 5 to 40. In a further advantageous embodiment, z is at least 10 to 26.

The TALE monomers can have a nucleotide binding affinity that is determined by the identity of the amino acids in its RVD. For example, polypeptide monomers with an RVD of NI can preferentially bind to adenine (A), monomers with an RVD of NG can preferentially bind to thymine (T), monomers with an RVD of HD can preferentially bind to cytosine (C) and monomers with an RVD of NN can preferentially bind to both adenine (A) and guanine (G). In some embodiments, monomers with an RVD of IG can preferentially bind to T. Thus, the number and order of the polypeptide monomer repeats in the nucleic acid binding domain of a TALE determines its nucleic acid target specificity. In some embodiments, monomers with an RVD of NS can recognize all four base pairs and can bind to A, T, G or C. The structure and function of TALEs is further described in, for example, Moscou et al., Science 326:1501 (2009); Boch et al., Science 326:1509-1512 (2009); and Zhang et al., Nature Biotechnology 29:149-153 (2011).

The polypeptides used in methods of the invention can be isolated, non-naturally occurring, recombinant or engineered nucleic acid-binding proteins that have nucleic acid or DNA binding regions containing polypeptide monomer repeats that are designed to target specific nucleic acid sequences.

As described herein, polypeptide monomers having an RVD of HN or NH preferentially bind to guanine and thereby allow the generation of TALE polypeptides with high binding specificity for guanine containing target nucleic acid sequences. In some embodiments, polypeptide monomers having RVDs RN, NN, NK, SN, NH, KN, HN, NQ, HH, RG, KH, RH and SS can preferentially bind to guanine. In some embodiments, polypeptide monomers having RVDs RN, NK, NQ, HH, KH, RH, SS and SN can preferentially bind to guanine and can thus allow the generation of TALE polypeptides with high binding specificity for guanine containing target nucleic acid sequences. In some embodiments, polypeptide monomers having RVDs HH, KH, NH, NK, NQ, RH, RN and SS can preferentially bind to guanine and thereby allow the generation of TALE polypeptides with high binding specificity for guanine containing target nucleic acid sequences. In some embodiments, the RVDs that have high binding specificity for guanine are RN, NH RH and KH. Furthermore, polypeptide monomers having an RVD of NV can preferentially bind to adenine and guanine. In some embodiments, monomers having RVDs of H*, HA, KA, N*, NA, NC, NS, RA, and S* bind to adenine, guanine, cytosine and thymine with comparable affinity.

The predetermined N-terminal to C-terminal order of the one or more polypeptide monomers of the nucleic acid or DNA binding domain determines the corresponding predetermined target nucleic acid sequence to which the polypeptides of the invention will bind. As used herein the monomers and at least one or more half monomers are “specifically ordered to target” the genomic locus or gene of interest. In plant genomes, the natural TALE-binding sites always begin with a thymine (T), which may be specified by a cryptic signal within the non-repetitive N-terminus of the TALE polypeptide; in some cases, this region may be referred to as repeat 0. In animal genomes, TALE binding sites do not necessarily have to begin with a thymine (T) and polypeptides of the invention may target DNA sequences that begin with T, A, G or C. The tandem repeat of TALE monomers always ends with a half-length repeat or a stretch of sequence that may share identity with only the first 20 amino acids of a repetitive full-length TALE monomer and this half repeat may be referred to as a half-monomer. Therefore, it follows that the length of the nucleic acid or DNA being targeted is equal to the number of full monomers plus two.

As described in Zhang et al., Nature Biotechnology 29:149-153 (2011), TALE polypeptide binding efficiency may be increased by including amino acid sequences from the “capping regions” that are directly N-terminal or C-terminal of the DNA binding region of naturally occurring TALEs into the engineered TALEs at positions N-terminal or C-terminal of the engineered TALE DNA binding region. Thus, in certain embodiments, the TALE polypeptides described herein further comprise an N-terminal capping region and/or a C-terminal capping region.

An exemplary amino acid sequence of a N-terminal capping region is:

(SEQ ID NO: 20)

MDPIRSRTPSPARELLSGPQPDGVQPTADRGVSPPAGGP

LDGLPARRTMSRTRLPSPPAPSPAFSADSFSDLLRQFDPSLFNTS

LFDSLPPFGAHHTEAATGEWDEVQSGLRAADAPPPTMRVAVTA

ARPPRAKPAPRRRAAQPSDASPAAQVDLRTLGYSQQQQEKIKP

KVRSTVAQHHEALVGHGFTHAHIVALSQHPAALGTVAVKYQD

MIAALPEATHEAIVGVGKQWSGARALEALLTVAGELRGPPLQL

DTGQLLKIAKRGGVTAVEAVHAWRNALTGAPLN

An exemplary amino acid sequence of a C-terminal capping region is:

(SEQ ID NO: 21)

RPALESIVAQLSRPDPALAALTNDHLVALACLGGRPAL

DAVKKGLPHAPALIKRTNRRIPERTSHRVADHAQVVRVLGFFQ

CHSHPAQAFDDAMTQFGMSRHGLLQLFRRVGVTELEARSGTLP

PASQRWDRILQASGMKRAKPSPTSTQTPDQASLHAFADSLERD

LDAPSPMHEGDQTRAS

As used herein the predetermined “N-terminus” to “C terminus” orientation of the N-terminal capping region, the DNA binding domain comprising the repeat TALE monomers and the C-terminal capping region provide structural basis for the organization of different domains in the d-TALEs or polypeptides of the invention.

The entire N-terminal and/or C-terminal capping regions are not necessary to enhance the binding activity of the DNA binding region. Therefore, in certain embodiments, fragments of the N-terminal and/or C-terminal capping regions are included in the TALE polypeptides described herein.

In certain embodiments, the TALE polypeptides described herein contain a N-terminal capping region fragment that included at least 10, 20, 30, 40, 50, 54, 60, 70, 80, 87, 90, 94, 100, 102, 110, 117, 120, 130, 140, 147, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260 or 270 amino acids of an N-terminal capping region. In certain embodiments, the N-terminal capping region fragment amino acids are of the C-terminus (the DNA-binding region proximal end) of an N-terminal capping region. As described in Zhang et al., Nature Biotechnology 29:149-153 (2011), N-terminal capping region fragments that include the C-terminal 240 amino acids enhance binding activity equal to the full length capping region, while fragments that include the C-terminal 147 amino acids retain greater than 80% of the efficacy of the full length capping region, and fragments that include the C-terminal 117 amino acids retain greater than 50% of the activity of the full-length capping region.

In some embodiments, the TALE polypeptides described herein contain a C-terminal capping region fragment that included at least 6, 10, 20, 30, 37, 40, 50, 60, 68, 70, 80, 90, 100, 110, 120, 127, 130, 140, 150, 155, 160, 170, 180 amino acids of a C-terminal capping region. In certain embodiments, the C-terminal capping region fragment amino acids are of the N-terminus (the DNA-binding region proximal end) of a C-terminal capping region. As described in Zhang et al., Nature Biotechnology 29:149-153 (2011), C-terminal capping region fragments that include the C-terminal 68 amino acids enhance binding activity equal to the full-length capping region, while fragments that include the C-terminal 20 amino acids retain greater than 50% of the efficacy of the full-length capping region.

In certain embodiments, the capping regions of the TALE polypeptides described herein do not need to have identical sequences to the capping region sequences provided herein. Thus, in some embodiments, the capping region of the TALE polypeptides described herein have sequences that are at least 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical or share identity to the capping region amino acid sequences provided herein. Sequence identity is related to sequence homology. Homology comparisons may be conducted by eye, or more usually, with the aid of readily available sequence comparison programs. These commercially available computer programs may calculate percent (%) homology between two or more sequences and may also calculate the sequence identity shared by two or more amino acid or nucleic acid sequences. In some preferred embodiments, the capping region of the TALE polypeptides described herein have sequences that are at least 95% identical or share identity to the capping region amino acid sequences provided herein.

Sequence homologies can be generated by any of a number of computer programs known in the art, which include but are not limited to BLAST or FASTA. Suitable computer programs for carrying out alignments like the GCG Wisconsin Bestfit package may also be used. Once the software has produced an optimal alignment, it is possible to calculate % homology, preferably % sequence identity. The software typically does this as part of the sequence comparison and generates a numerical result.

In some embodiments described herein, the TALE polypeptides of the invention include a nucleic acid binding domain linked to the one or more effector domains. The terms “effector domain” or “regulatory and functional domain” refer to a polypeptide sequence that has an activity other than binding to the nucleic acid sequence recognized by the nucleic acid binding domain. By combining a nucleic acid binding domain with one or more effector domains, the polypeptides of the invention may be used to target the one or more functions or activities mediated by the effector domain to a particular target DNA sequence to which the nucleic acid binding domain specifically binds.

In some embodiments of the TALE polypeptides described herein, the activity mediated by the effector domain is a biological activity. For example, in some embodiments the effector domain is a transcriptional inhibitor (i.e., a repressor domain), such as an mSin interaction domain (SID). SID4X domain or a Kruppel-associated box (KRAB) or fragments of the KRAB domain. In some embodiments the effector domain is an enhancer of transcription (i.e. an activation domain), such as the VP16, VP64 or p65 activation domain. In some embodiments, the nucleic acid binding is linked, for example, with an effector domain that includes but is not limited to a transposase, integrase, recombinase, resolvase, invertase, protease, DNA methyltransferase, DNA demethylase, histone acetylase, histone deacetylase, nuclease, transcriptional repressor, transcriptional activator, transcription factor recruiting, protein nuclear-localization signal or cellular uptake signal.

In some embodiments, the effector domain is a protein domain which exhibits activities which include but are not limited to transposase activity, integrase activity, recombinase activity, resolvase activity, invertase activity, protease activity, DNA methyltransferase activity, DNA demethylase activity, histone acetylase activity, histone deacetylase activity, nuclease activity, nuclear-localization signaling activity, transcriptional repressor activity, transcriptional activator activity, transcription factor recruiting activity, or cellular uptake signaling activity. Other preferred embodiments of the invention may include any combination of the activities described herein.

Meganucleases

In some embodiments, a meganuclease or system thereof can be used to modify a target polynucleotide. Meganucleases, which are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs). Exemplary methods for using meganucleases can be found in U.S. Pat. Nos. 8,163,514, 8,133,697, 8,021,867, 8,119,361, 8,119,381, 8,124,369, and 8,129,134, which are specifically incorporated by reference.

RNAi

In certain embodiments, the genetic modifying agent is RNAi (e.g., shRNA). As used herein, “gene silencing” or “gene silenced” in reference to an activity of an RNAi molecule, for example a siRNA or miRNA refers to a decrease in the mRNA level in a cell for a target gene by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 99%, about 100% of the mRNA level found in the cell without the presence of the miRNA or RNA interference molecule. In one preferred embodiment, the mRNA levels are decreased by at least about 70%, about 80%, about 90%, about 95%, about 99%, about 100%.

As used herein, the term “RNAi” refers to any type of interfering RNA, including but not limited to, siRNAi, shRNAi, endogenous microRNA and artificial microRNA. For instance, it includes sequences previously identified as siRNA, regardless of the mechanism of down-stream processing of the RNA (i.e. although siRNAs are believed to have a specific method of in vivo processing resulting in the cleavage of mRNA, such sequences can be incorporated into the vectors in the context of the flanking sequences described herein). The term “RNAi” can include both gene silencing RNAi molecules, and also RNAi effector molecules which activate the expression of a gene.

As used herein, a “siRNA” refers to a nucleic acid that forms a double stranded RNA, which double stranded RNA has the ability to reduce or inhibit expression of a gene or target gene when the siRNA is present or expressed in the same cell as the target gene. The double stranded RNA siRNA can be formed by the complementary strands. In one embodiment, a siRNA refers to a nucleic acid that can form a double stranded siRNA. The sequence of the siRNA can correspond to the full-length target gene, or a subsequence thereof. Typically, the siRNA is at least about 15-50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is about 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length, preferably about 19-30 base nucleotides, preferably about 20-25 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length).

As used herein “shRNA” or “small hairpin RNA” (also called stem loop) is a type of siRNA. In one embodiment, these shRNAs are composed of a short, e.g. about 19 to about 25 nucleotide, antisense strand, followed by a nucleotide loop of about 5 to about 9 nucleotides, and the analogous sense strand. Alternatively, the sense strand can precede the nucleotide loop structure and the antisense strand can follow.

The terms “microRNA” or “miRNA” are used interchangeably herein are endogenous RNAs, some of which are known to regulate the expression of protein-coding genes at the posttranscriptional level. Endogenous microRNAs are small RNAs naturally present in the genome that are capable of modulating the productive utilization of mRNA. The term artificial microRNA includes any type of RNA sequence, other than endogenous microRNA, which is capable of modulating the productive utilization of mRNA. MicroRNA sequences have been described in publications such as Lim, et al., Genes & Development, 17, p. 991-1008 (2003), Lim et al Science 299, 1540 (2003), Lee and Ambros Science, 294, 862 (2001), Lau et al., Science 294, 858-861 (2001), Lagos-Quintana et al, Current Biology, 12, 735-739 (2002), Lagos Quintana et al, Science 294, 853-857 (2001), and Lagos-Quintana et al, RNA, 9, 175-179 (2003), which are incorporated by reference. Multiple microRNAs can also be incorporated into a precursor molecule. Furthermore, miRNA-like stem-loops can be expressed in cells as a vehicle to deliver artificial miRNAs and short interfering RNAs (siRNAs) for the purpose of modulating the expression of endogenous genes through the miRNA and or RNAi pathways.

As used herein, “double stranded RNA” or “dsRNA” refers to RNA molecules that are comprised of two strands. Double-stranded molecules include those comprised of a single RNA molecule that doubles back on itself to form a two-stranded structure. For example, the stem loop structure of the progenitor molecules from which the single-stranded miRNA is derived, called the pre-miRNA (Bartel et al. 2004. Cell 1 16:281-297), comprises a dsRNA molecule.

Diseases

It will be understood by the skilled person that treating as referred to herein encompasses enhancing treatment, or improving treatment efficacy. Treatment may include inhibition of an inflammatory response, enhancing an immune response, tumor regression as well as inhibition of tumor growth, metastasis or tumor cell proliferation, or inhibition or reduction of otherwise deleterious effects associated with the tumor.

Efficaciousness of treatment is determined in association with any known method for diagnosing or treating the particular disease. The invention comprehends a treatment method comprising any one of the methods or uses herein discussed.

The phrase “therapeutically effective amount” as used herein refers to a sufficient amount of a drug, agent, or compound to provide a desired therapeutic effect.

As used herein “patient” refers to any human being receiving or who may receive medical treatment and is used interchangeably herein with the term “subject”.

Therapy or treatment according to the invention may be performed alone or in conjunction with another therapy, and may be provided at home, the doctor's office, a clinic, a hospital's outpatient department, or a hospital. Treatment generally begins at a hospital so that the doctor can observe the therapy's effects closely and make any adjustments that are needed. The duration of the therapy depends on the age and condition of the patient, the stage of the cancer, and how the patient responds to the treatment. Additionally, a person having a greater risk of developing an inflammatory response (e.g., a person who is genetically predisposed or predisposed to allergies or a person having a disease characterized by episodes of inflammation) may receive prophylactic treatment to inhibit or delay symptoms of the disease.

The disclosure provides CGRP or derivatives thereof, or an agonist of the CGRP receptor for treating disease. A skilled person can readily determine diseases that can be treated by reducing an ILC2 inflammatory response. ILC2 cells and ILC2 inflammatory responses have been associated with allergic asthma, therapy resistant-asthma, steroid-resistant severe allergic airway inflammation, systemic steroid-dependent severe eosinophilic asthma, chronic rhino-sinusitis (CRS), atopic dermatitis, food allergies, persistence of chronic airway inflammation, and primary eosinophilic gastrointestinal disorders (EGIDs), including but not limited to eosinophilic esophagitis (EoE), eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis (see, e.g., Van Rijt et al., Type 2 innate lymphoid cells: at the cross-roads in allergic asthma, Seminars in Immunopathology July 2016, Volume 38, Issue 4, pp 483-496; Rivas et al., IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function, J Allergy Clin Immunol. 2016 September; 138(3):801-811.e9; and Morita, Hideaki et al. Innate lymphoid cells in allergic and nonallergic inflammation, Journal of Allergy and Clinical Immunology, Volume 138, Issue 5, 1253-1264). Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. Sputum may be produced from the lung by coughing but is often hard to bring up. During recovery from an attack, it may appear pus-like due to high levels of eosinophils. Symptoms are usually worse at night and in the early morning or in response to exercise or cold air. Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may have marked and persistent symptoms. CRS is characterized by inflammation of the mucosal surfaces of the nose and para-nasal sinuses, and it often coexists with allergic asthma. Atopic dermatitis is a chronic inflammatory skin disease that is characterized by eosinophilic infiltration and high serum IgE levels. Similar to allergic asthma and CRS, atopic dermatitis has been associated with increased expression of TSLP, IL-25, and IL-33 in the skin. Primary eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EoE), eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitisare disorders that exhibit eosinophil-rich inflammation in the gastrointestinal tract in the absence of known causes for eosinophilia such as parasite infection and drug reaction. Not being bound by a theory, corticosteroids suppress TH2 cells, but not ILC2s and cannot be used to modulate ILC2 inflammatory responses. Applicants have discovered factors that balance homeostatic and pathological pro-inflammatory ILC2 responses. In certain embodiments, modulation of these factors, as described herein, may be used to treat the diseases described. In preferred embodiments, CGRP signaling is modulated. In certain embodiments, the treatment can maintain homeostasis of intestinal KLRG^HiST2⁻ILC2s and prevent their migration to peripheral sites (e.g., lungs) (see, Huang et al., 2017).

In certain embodiments an ILC2 mediated disease or disorder that can be treated by reducing an ILC2 inflammatory response or maintaining ILC2 homeostasis may be any inflammatory disease or disorder such as, but not limited to, asthma, allergy, allergic rhinitis, allergic airway inflammation, atopic dermatitis (AD), chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), multiple sclerosis, arthritis, psoriasis, eosinophilic esophagitis, eosinophilic pneumonia, eosinophilic psoriasis, hypereosinophilic syndrome, graft-versus-host disease, uveitis, cardiovascular disease, pain, multiple sclerosis, lupus, vasculitis, chronic idiopathic urticaria and Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome).

The asthma may be allergic asthma, non-allergic asthma, severe refractory asthma, asthma exacerbations, viral-induced asthma or viral-induced asthma exacerbations, steroid resistant asthma, steroid sensitive asthma, eosinophilic asthma or non-eosinophilic asthma and other related disorders characterized by airway inflammation or airway hyperresponsiveness (AHR).

The COPD may be a disease or disorder associated in part with, or caused by, cigarette smoke, air pollution, occupational chemicals, allergy or airway hyperresponsiveness.

The allergy may be associated with foods, pollen, mold, dust mites, animals, or animal dander.

The IBD may be ulcerative colitis (UC), Crohn's Disease, collagenous colitis, lymphocytic colitis, ischemic colitis, diversion colitis, Behcet's syndrome, infective colitis, indeterminate colitis, and other disorders characterized by inflammation of the mucosal layer of the large intestine or colon.

The arthritis may be selected from the group consisting of osteoarthritis, rheumatoid arthritis and psoriatic arthritis.

The disclosure also provides methods for enhancing an ILC2 type response and treating disease. In certain embodiments, tissue inflammatory ILC2s are switched to activated, tissue protective ILC2s. ILC2 cells have been shown to promote an eosinophil cytotoxic response, antitumor response and metastasis suppression (Ikutani et al., Identification of Innate IL-5-Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity, J Immunol 2012; 188:703-713). Specifically, innate IL-5-producing cells were increased in response to tumor invasion, and their regulation of eosinophils was critical to suppress tumor metastasis. Thus, in one embodiment induction of an ILC2 inflammatory response may be used in treating cancer. In other embodiments, the cancer is resistant to therapies targeting the adaptive immune system (see e.g., Rooney et al., Molecular and genetic properties of tumors associated with local immune cytolytic activity, Cell. 2015 January 15; 160(1-2): 48-61). In one embodiment, modulation of CGRP signaling is used for inducing an inflammatory immune response state for the treatment of a subpopulation of tumor cells that are linked to resistance to targeted therapies and progressive tumor growth. Not being bound by a theory, in cases where tumors are resistant to therapies targeting the adaptive immune system, treatments targeting the innate immune system may be therapeutically effective in treating the tumor.

The cancer may include, without limitation, liquid tumors such as leukemia (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (e.g., Hodgkin's disease, non-Hodgkin's disease), Waldenstrom's macroglobulinemia, heavy chain disease, or multiple myeloma.

The cancer may include, without limitation, solid tumors such as sarcomas and carcinomas. Examples of solid tumors include, but are not limited to fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, epithelial carcinoma, bronchogenic carcinoma, hepatoma, colorectal cancer (e.g., colon cancer, rectal cancer), anal cancer, pancreatic cancer (e.g., pancreatic adenocarcinoma, islet cell carcinoma, neuroendocrine tumors), breast cancer (e.g., ductal carcinoma, lobular carcinoma, inflammatory breast cancer, clear cell carcinoma, mucinous carcinoma), ovarian carcinoma (e.g., ovarian epithelial carcinoma or surface epithelial-stromal tumour including serous tumour, endometrioid tumor and mucinous cystadenocarcinoma, sex-cord-stromal tumor), prostate cancer, liver and bile duct carcinoma (e.g., hepatocelluar carcinoma, cholangiocarcinoma, hemangioma), choriocarcinoma, seminoma, embryonal carcinoma, kidney cancer (e.g., renal cell carcinoma, clear cell carcinoma, Wilm's tumor, nephroblastoma), cervical cancer, uterine cancer (e.g., endometrial adenocarcinoma, uterine papillary serous carcinoma, uterine clear-cell carcinoma, uterine sarcomas and leiomyosarcomas, mixed mullerian tumors), testicular cancer, germ cell tumor, lung cancer (e.g., lung adenocarcinoma, squamous cell carcinoma, large cell carcinoma, bronchioloalveolar carcinoma, non-small-cell carcinoma, small cell carcinoma, mesothelioma), bladder carcinoma, signet ring cell carcinoma, cancer of the head and neck (e.g., squamous cell carcinomas), esophageal carcinoma (e.g., esophageal adenocarcinoma), tumors of the brain (e.g., glioma, glioblastoma, medullablastoma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodenroglioma, schwannoma, meningioma), neuroblastoma, retinoblastoma, neuroendocrine tumor, melanoma, cancer of the stomach (e.g., stomach adenocarcinoma, gastrointestinal stromal tumor), or carcinoids. Lymphoproliferative disorders are also considered to be proliferative diseases.

Administration

In certain embodiments, proteins are administered to a subject in need thereof (e.g., CGRP, antibodies). Delivery of therapeutic proteins can be performed according to any method known in the art (see, e.g., Pisal et al., DELIVERY OF THERAPEUTIC PROTEINS, J Pharm Sci. 2010 June; 99(6): 2557-2575; and Cleland et al., Emerging protein delivery methods, Curr Opin Biotechnol. 2001 April; 12(2):212-9.

It will be appreciated that administration of therapeutic entities in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like. A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences (15th ed, Mack Publishing Company, Easton, Pa. (1975)), particularly Chapter 87 by Blaug, Seymour, therein. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as Lipofectin™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax. Any of the foregoing mixtures may be appropriate in treatments and therapies in accordance with the present invention, provided that the active ingredient in the formulation is not inactivated by the formulation and the formulation is physiologically compatible and tolerable with the route of administration. See also Baldrick P. “Pharmaceutical excipient development: the need for preclinical guidance.” Regul. Toxicol Pharmacol. 32(2):210-8 (2000), Wang W. “Lyophilization and development of solid protein pharmaceuticals.” Int. J. Pharm. 203(1-2):1-60 (2000), Charman W N “Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts.” J Pharm Sci. 89(8):967-78 (2000), Powell et al. “Compendium of excipients for parenteral formulations” PDA J Pharm Sci Technol. 52:238-311 (1998) and the citations therein for additional information related to formulations, excipients and carriers well known to pharmaceutical chemists.

The medicaments of the invention are prepared in a manner known to those skilled in the art, for example, by means of conventional dissolving, lyophilizing, mixing, granulating or confectioning processes. Methods well known in the art for making formulations are found, for example, in Remington: The Science and Practice of Pharmacy, 20th ed., ed. A. R. Gennaro, 2000, Lippincott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 1988-1999, Marcel Dekker, New York.

Administration of medicaments of the invention may be by any suitable means that results in a compound concentration that is effective for treating or inhibiting (e.g., by delaying) the development of a disease. The compound is admixed with a suitable carrier substance, e.g., a pharmaceutically acceptable excipient that preserves the therapeutic properties of the compound with which it is administered. One exemplary pharmaceutically acceptable excipient is physiological saline. The suitable carrier substance is generally present in an amount of 1-95% by weight of the total weight of the medicament. The medicament may be provided in a dosage form that is suitable for administration. Thus, the medicament may be in form of, e.g., tablets, capsules, pills, powders, granulates, suspensions, emulsions, solutions, gels including hydrogels, pastes, ointments, creams, plasters, drenches, delivery devices, injectables, implants, sprays, or aerosols.

The agents disclosed herein (e.g., CGRP, CGRP receptor agonists or antagonists) may be used in a pharmaceutical composition when combined with a pharmaceutically acceptable carrier. Such compositions comprise a therapeutically-effective amount of the agent and a pharmaceutically acceptable carrier. Such a composition may also further comprise (in addition to an agent and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. Compositions comprising the agent can be administered in the form of salts provided the salts are pharmaceutically acceptable. Salts may be prepared using standard procedures known to those skilled in the art of synthetic organic chemistry.

The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids including inorganic or organic bases and inorganic or organic acids. Salts derived from inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic salts, manganous, potassium, sodium, zinc, and the like. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as arginine, betaine, caffeine, choline, N,N′-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethyl-morpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine, and the like. The term “pharmaceutically acceptable salt” further includes all acceptable salts such as acetate, lactobionate, benzenesulfonate, laurate, benzoate, malate, bicarbonate, maleate, bisulfate, mandelate, bitartrate, mesylate, borate, methylbromide, bromide, methylnitrate, calcium edetate, methyl sulfate, camsylate, mucate, carbonate, napsylate, chloride, nitrate, clavulanate, N-methylglucamine, citrate, ammonium salt, dihydrochloride, oleate, edetate, oxalate, edisylate, pamoate (embonate), estolate, palmitate, esylate, pantothenate, fumarate, phosphate/diphosphate, gluceptate, polygalacturonate, gluconate, salicylate, glutamate, stearate, glycollylarsanilate, sulfate, hexylresorcinate, subacetate, hydrabamine, succinate, hydrobromide, tannate, hydrochloride, tartrate, hydroxynaphthoate, teoclate, iodide, tosylate, isothionate, triethiodide, lactate, panoate, valerate, and the like which can be used as a dosage form for modifying the solubility or hydrolysis characteristics or can be used in sustained release or pro-drug formulations. It will be understood that, as used herein, references to specific agents (e.g., CGRP receptor agonists or antagonists), also include the pharmaceutically acceptable salts thereof.

Methods of administrating the pharmacological compositions, including CGRP, agonists, antagonists, antibodies or fragments thereof, to an individual include, but are not limited to, intradermal, intrathecal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, by inhalation, and oral routes. In preferred embodiments, CGRP protein is administered intraperitoneally as described in the examples. The compositions can be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (for example, oral mucosa, rectal and intestinal mucosa, and the like), ocular, and the like and can be administered together with other biologically-active agents. Administration can be systemic or local. In addition, it may be advantageous to administer the composition into the central nervous system by any suitable route, including intraventricular and intrathecal injection. Pulmonary administration may also be employed by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. It may also be desirable to administer the agent locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion during surgery, topical application, by injection, by means of a catheter, by means of a suppository, or by means of an implant.

Various delivery systems are known and can be used to administer the pharmacological compositions including, but not limited to, encapsulation in liposomes, microparticles, microcapsules; minicells; polymers; capsules; tablets; and the like. In one embodiment, the agent may be delivered in a vesicle, in particular a liposome. In a liposome, the agent is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Pat. Nos. 4,837,028 and 4,737,323. In yet another embodiment, the pharmacological compositions can be delivered in a controlled release system including, but not limited to: a delivery pump (See, for example, Saudek, et al., New Engl. J. Med. 321: 574 (1989) and a semi-permeable polymeric material (See, for example, Howard, et al., J. Neurosurg. 71: 105 (1989)). Additionally, the controlled release system can be placed in proximity of the therapeutic target (e.g., a tumor), thus requiring only a fraction of the systemic dose. See, for example, Goodson, In: Medical Applications of Controlled Release, 1984. (CRC Press, Boca Raton, Fla.).

The amount of the agents (e.g., CGRP, CGRP receptor agonist) which will be effective in the treatment of a particular disorder or condition will depend on the nature of the disorder or condition, and may be determined by standard clinical techniques by those of skill within the art. In addition, in vitro assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation will also depend on the route of administration, and the overall seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. Ultimately, the attending physician will decide the amount of the agent with which to treat each individual patient. In certain embodiments, the attending physician will administer low doses of the agent and observe the patient's response. Larger doses of the agent may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. In general, the daily dose range lie within the range of from about 0.001 mg to about 100 mg per kg body weight of a mammal, preferably 0.01 mg to about 50 mg per kg, and most preferably 0.1 to 10 mg per kg, in single or divided doses. On the other hand, it may be necessary to use dosages outside these limits in some cases. In certain embodiments, suitable dosage ranges for intravenous administration of the agent (e.g., intraperitoneal CGRP administration) are generally about 0.1-500 micrograms (μg) of active compound per kilogram (Kg) body weight, preferably about 0.1-0.5 μg/kg. Suitable dosage ranges for intranasal administration are generally about 0.01 pg/kg body weight to 1 mg/kg body weight. In certain embodiments, a composition containing an agent of the present invention is subcutaneously injected in adult patients with dose ranges of approximately 5 to 5000 μg/human and preferably approximately 5 to 500 μg/human as a single dose. It is desirable to administer this dosage 1 to 3 times daily. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. Suppositories generally contain active ingredient in the range of 0.5% to 10% by weight; oral formulations preferably contain 10% to 95% active ingredient. Ultimately the attending physician will decide on the appropriate duration of therapy using compositions of the present invention. Dosage will also vary according to the age, weight and response of the individual patient.

Methods for administering antibodies for therapeutic use is well known to one skilled in the art. In certain embodiments, small particle aerosols of antibodies or fragments thereof may be administered (see e.g., Piazza et al., J. Infect. Dis., Vol. 166, pp. 1422-1424, 1992; and Brown, Aerosol Science and Technology, Vol. 24, pp. 45-56, 1996). In certain embodiments, antibodies (e.g., anti-CGRP receptor or anti-CGRP antibodies) are administered in metered-dose propellant driven aerosols. In preferred embodiments, antibodies are used as agonists to depress inflammatory diseases or allergen-induced asthmatic responses. In certain embodiments, antibodies may be administered in liposomes, i.e., immunoliposomes (see, e.g., Maruyama et al., Biochim. Biophys. Acta, Vol. 1234, pp. 74-80, 1995). In certain embodiments, immunoconjugates, immunoliposomes or immunomicrospheres containing an agent of the present invention is administered by inhalation.

In certain embodiments, antibodies may be topically administered to mucosa, such as the oropharynx, nasal cavity, respiratory tract, gastrointestinal tract, eye such as the conjunctival mucosa, vagina, urogenital mucosa, or for dermal application. In certain embodiments, antibodies are administered to the nasal, bronchial or pulmonary mucosa. In order to obtain optimal delivery of the antibodies to the pulmonary cavity in particular, it may be advantageous to add a surfactant such as a phosphoglyceride, e.g. phosphatidylcholine, and/or a hydrophilic or hydrophobic complex of a positively or negatively charged excipient and a charged antibody of the opposite charge.

Other excipients suitable for pharmaceutical compositions intended for delivery of antibodies to the respiratory tract mucosa may be a) carbohydrates, e.g., monosaccharides such as fructose, galactose, glucose. D-mannose, sorbiose, and the like; disaccharides, such as lactose, trehalose, cellobiose, and the like; cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin; and polysaccharides, such as raffinose, maltodextrins, dextrans, and the like; b) amino acids, such as glycine, arginine, aspartic acid, glutamic acid, cysteine, lysine and the like; c) organic salts prepared from organic acids and bases, such as sodium citrate, sodium ascorbate, magnesium gluconate, sodium gluconate, tromethamine hydrochloride, and the like: d) peptides and proteins, such as aspartame, human serum albumin, gelatin, and the like; e) alditols, such mannitol, xylitol, and the like, and f) polycationic polymers, such as chitosan or a chitosan salt or derivative.

For dermal application, the antibodies of the present invention may suitably be formulated with one or more of the following excipients: solvents, buffering agents, preservatives, humectants, chelating agents, antioxidants, stabilizers, emulsifying agents, suspending agents, gel-forming agents, ointment bases, penetration enhancers, and skin protective agents.

Examples of solvents are water, alcohols, vegetable or marine oils (e.g. edible oils like almond oil, castor oil, cacao butter, coconut oil, corn oil, cottonseed oil, linseed oil, olive oil, palm oil, peanut oil, poppy seed oil, rapeseed oil, sesame oil, soybean oil, sunflower oil, and tea seed oil), mineral oils, fatty oils, liquid paraffin, polyethylene glycols, propylene glycols, glycerol, liquid polyalkylsiloxanes, and mixtures thereof.

Examples of buffering agents are citric acid, acetic acid, tartaric acid, lactic acid, hydrogenphosphoric acid, diethyl amine etc. Suitable examples of preservatives for use in compositions are parabenes, such as methyl, ethyl, propyl p-hydroxybenzoate, butylparaben, isobutylparaben, isopropylparaben, potassium sorbate, sorbic acid, benzoic acid, methyl benzoate, phenoxyethanol, bronopol, bronidox, MDM hydantoin, iodopropynyl butylcarbamate, EDTA, benzalconium chloride, and benzylalcohol, or mixtures of preservatives.

Examples of humectants are glycerin, propylene glycol, sorbitol, lactic acid, urea, and mixtures thereof.

Examples of antioxidants are butylated hydroxy anisole (BHA), ascorbic acid and derivatives thereof, tocopherol and derivatives thereof, cysteine, and mixtures thereof.

Examples of emulsifying agents are naturally occurring gums, e.g., gum acacia or gum tragacanth; naturally occurring phosphatides, e.g., soybean lecithin, sorbitan monooleate derivatives: wool fats; wool alcohols; sorbitan esters; monoglycerides; fatty alcohols; fatty acid esters (e.g,. triglycerides of fatty acids); and mixtures thereof.

Examples of suspending agents are celluloses and cellulose derivatives such as, e.g., carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carraghenan, acacia gum, arabic gum, tragacanth, and mixtures thereof.

Examples of gel bases, viscosity-increasing agents or components which are able to take up exudate from a wound are liquid paraffin, polyethylene, fatty oils, colloidal silica or aluminum, zinc soaps, glycerol, propylene glycol, tragacanth, carboxyvinyl polymers, magnesium-aluminum silicates, Carbopol®, hydrophilic polymers such as, e.g. starch or cellulose derivatives such as, e.g., carboxymethylcellulose, hydroxyethylcellulose and other cellulose derivatives, water-swellable hydrocolloids, carragenans, hyaluronates (e.g., hyaluronate gel optionally containing sodium chloride), and alginates including propylene glycol alginate.

Examples of ointment bases are e.g. beeswax, paraffin, cetanol, cetyl palmitate, vegetable oils, sorbitan esters of fatty acids (Span), polyethylene glycols, and condensation products between sorbitan esters of fatty acids and ethylene oxide, e.g. polyoxyethylene sorbitan monooleate (Tween).

Examples of hydrophobic or water-emulsifying ointment bases are paraffins, vegetable oils, animal fats, synthetic glycerides, waxes, lanolin, and liquid polyalkylsiloxanes. Examples of hydrophilic ointment bases are solid macrogols (polyethylene glycols). Other examples of ointment bases are triethanolamine soaps, sulphated fatty alcohol and polysorbates.

Examples of other excipients are polymers such as carmelose, sodium carmelose, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, pectin, xanthan gum, locust bean gum, acacia gum, gelatin, carbomer, emulsifiers like vitamin E, glyceryl stearates, cetanyl glucoside, collagen, carrageenan, hyaluronates and alginates and chitosans.

The dose of antibody required in humans to be effective in the treatment or prevention of allergic inflammation differs with the type and severity of the allergic condition to be treated, the type of allergen, the age and condition of the patient, etc. Typical doses of antibody to be administered are in the range of 1 μg to 1 g, preferably 1-1000 more preferably 2-500, even more preferably 5-50, most preferably 10-20 μg per unit dosage form. In certain embodiments, infusion of antibodies of the present invention may range from 10-500 mg/m².

The one or more therapeutic molecules may be expressed from one or more polynucleotide sequences on one or more vectors (e.g., CGRP, genetic modifying agent). The invention comprehends such polynucleotide molecule(s), for instance such polynucleotide molecules operably configured to express the protein and/or the nucleic acid component(s), as well as such vector(s). Regulatory elements may comprise inducible promotors. Polynucleotides and/or vector systems may comprise inducible systems. For example, the expression of the polynucleotides may be regulated by a tetracycline/doxycycline controlled inducible promoter. In certain embodiments, the vectors are tissue specific. The vector may include a tissue specific regulatory element or be a tissue specific vector (e.g., viral vector).

In general, and throughout this specification, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. Vectors include, but are not limited to, nucleic acid molecules that are single-stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, no free ends (e.g., circular); nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. One type of vector is a “plasmid,” which refers to a circular double stranded DNA loop into which additional DNA segments can be inserted, such as by standard molecular cloning techniques. Another type of vector is a viral vector, wherein virally-derived DNA or RNA sequences are present in the vector for packaging into a virus (e.g., retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses). Viral vectors also include polynucleotides carried by a virus for transfection into a host cell. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors.” Vectors for and that result in expression in a eukaryotic cell can be referred to herein as “eukaryotic expression vectors.” Common expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. The vectors used herein may include viral vectors or plasmids. In preferred embodiments, viral vectors are used. In more preferred embodiments, lentiviral vectors are used.

In certain embodiments, the vectors used can include a detectable or selectable marker used to select for cells that were transfected or transduced. Selection can use FACS or any cell sorting method. Cells can be selected for by use of a drug resistance marker. In certain embodiments, the detectable marker is a fluorescent protein such as green fluorescent protein (GFP), enhanced green fluorescent protein (EGFP), red fluorescent protein (RFP), blue fluorescent protein (BFP), cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), miRFP (e.g., miRFP670, see, e.g., Shcherbakova, et al., Nat Commun. 2016; 7: 12405), mCherry, tdTomato, DsRed-Monomer, DsRed-Express, DSRed-Express2, DsRed2, AsRed2, mStrawberry, mPlum, mRaspberry, HcRedl, E2-Crimson, mOrange, mOrange2, mBanana, ZsYellowl, TagBFP, mTagBFP2, Azurite, EBFP2, mKalamal, Sirius, Sapphire, T-Sapphire, ECFP, Cerulean, SCFP3A, mTurquoise, mTurquoise2, monomelic Midoriishi-Cyan, TagCFP, niTFPl, Emerald, Superfolder GFP, Monomeric Azami Green, TagGFP2, mUKG, mWasabi, Clover, mNeonGreen, Citrine, Venus, SYFP2, TagYFP, Monomeric Kusabira-Orange, mKOk, mK02, mTangerine, mApple, mRuby, mRuby2, HcRed-Tandem, mKate2, mNeptune, NiFP, mkeima Red, LSS-mKatel, LSS-mKate2, mBeRFP, PA-GFP, PAmCherryl, PATagRFP, TagRFP6457, IFP1.2, iRFP, Kaede (green), Kaede (red), KikGRl (green), KikGRl (red), PS-CFP2, mEos2 (green), mEos2 (red), mEos3.2 (green), mEos3.2 (red), PSmOrange, Dronpa, Dendra2, Timer, AmCyanl, or a combination thereof. In certain embodiments, the detectable marker is a cell surface marker. In other instances, the cell surface marker is a marker not normally expressed on the cells, such as a truncated nerve growth factor receptor (tNGFR), a truncated epidermal growth factor receptor (tEGFR), CD8, truncated CD8, CD19, truncated CD19, a variant thereof, a fragment thereof, a derivative thereof, or a combination thereof. Selectable markers are known in the art and enable selecting for cells having the barcode integrated. Examples of selectable markers include, but are not limited to, antibiotic resistance genes, such as beta-lactamase, neo, FabI, URA3, cam, tet, blasticidin, hyg, puromycin and the like. A selectable marker useful in accordance with the invention may be any selectable marker appropriate for use in a eukaryotic cell, such as a mammalian cell, or more specifically a human cell. One of skill in the art will understand and be able to identify and use selectable markers in accordance with the invention.

The invention also provides a delivery system comprising one or more vectors or one or more polynucleotide molecules, the one or more vectors or polynucleotide molecules comprising one or more polynucleotide molecules encoding components of a non-naturally occurring or engineered composition which is a composition having the characteristics as discussed herein or defined in any of the herein described methods.

The invention also provides a non-naturally occurring or engineered composition, or one or more polynucleotides encoding components of said composition, or delivery systems comprising one or more polynucleotides encoding components of said composition for use in a therapeutic method of treatment. The therapeutic method of treatment may comprise gene or genome editing, or gene therapy.

Delivery vehicles, vectors, particles, nanoparticles, formulations and components thereof for expression of one or more elements of a nucleic acid-targeting system are as used in the foregoing documents, such as WO 2014/093622 (PCT/US2013/074667). In some embodiments, a vector comprises one or more insertion sites, such as a restriction endonuclease recognition sequence (also referred to as a “cloning site”). In some embodiments, one or more insertion sites (e.g., about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more insertion sites) are located upstream and/or downstream of one or more sequence elements of one or more vectors.

The invention also provides an expression vector comprising any of the above-described polynucleotide molecules. The invention also provides such polynucleotide molecule(s), for instance such polynucleotide molecules operably configured to express the protein and/or the nucleic acid component(s), as well as such vector(s).

In practicing any of the methods disclosed herein, a suitable vector can be introduced to a cell or an embryo via one or more methods known in the art, including without limitation, microinjection, electroporation, sonoporation, biolistics, calcium phosphate-mediated transfection, cationic transfection, liposome transfection, dendrimer transfection, heat shock transfection, nucleofection transfection, magnetofection, lipofection, impalefection, optical transfection, proprietary agent-enhanced uptake of nucleic acids, and delivery via liposomes, immunoliposomes, virosomes, or artificial virions. In some methods, the vector is introduced into an embryo by microinjection. The vector or vectors may be microinjected into the nucleus or the cytoplasm of the embryo. In some methods, the vector or vectors may be introduced into a cell by nucleofection.

There are a variety of techniques available for introducing nucleic acids into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host. Techniques suitable for the transfer of nucleic acid into mammalian cells in vitro include the use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. The currently preferred in vivo gene transfer techniques include transfection with viral (typically retroviral) vectors and viral coat protein-liposome mediated transfection.

In another aspect, provided is a pharmaceutical pack or kit, comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions and CGRP receptor agonists or antagonists (e.g., CGRP).

Diagnostic and Screening Methods

The invention provides biomarkers (e.g., phenotype specific or cell type) for the identification, diagnosis, prognosis and manipulation of cell properties, for use in a variety of diagnostic and/or therapeutic indications. Biomarkers in the context of the present invention encompasses, without limitation nucleic acids, proteins, reaction products, and metabolites, together with their polymorphisms, mutations, variants, modifications, subunits, fragments, and other analytes or sample-derived measures. In certain embodiments, biomarkers include the signature genes or signature gene products, and/or cells as described herein.

Biomarkers are useful in methods of diagnosing, prognosing and/or staging an immune response in a subject by detecting a first level of expression, activity and/or function of one or more biomarker and comparing the detected level to a control of level wherein a difference in the detected level and the control level indicates that the presence of an immune response in the subject.

The terms “diagnosis” and “monitoring” are commonplace and well-understood in medical practice. By means of further explanation and without limitation the term “diagnosis” generally refers to the process or act of recognising, deciding on or concluding on a disease or condition in a subject on the basis of symptoms and signs and/or from results of various diagnostic procedures (such as, for example, from knowing the presence, absence and/or quantity of one or more biomarkers characteristic of the diagnosed disease or condition).

The terms “prognosing” or “prognosis” generally refer to an anticipation on the progression of a disease or condition and the prospect (e.g., the probability, duration, and/or extent) of recovery. A good prognosis of the diseases or conditions taught herein may generally encompass anticipation of a satisfactory partial or complete recovery from the diseases or conditions, preferably within an acceptable time period. A good prognosis of such may more commonly encompass anticipation of not further worsening or aggravating of such, preferably within a given time period. A poor prognosis of the diseases or conditions as taught herein may generally encompass anticipation of a substandard recovery and/or unsatisfactorily slow recovery, or to substantially no recovery or even further worsening of such.

The biomarkers of the present invention are useful in methods of identifying patient populations at risk or suffering from an immune response based on a detected level of expression, activity and/or function of one or more biomarkers. These biomarkers are also useful in monitoring subjects undergoing treatments and therapies for suitable or aberrant response(s) to determine efficaciousness of the treatment or therapy and for selecting or modifying therapies and treatments that would be efficacious in treating, delaying the progression of or otherwise ameliorating a symptom. The biomarkers provided herein are useful for selecting a group of patients at a specific state of a disease with accuracy that facilitates selection of treatments.

The term “monitoring” generally refers to the follow-up of a disease or a condition in a subject for any changes which may occur over time.

The terms also encompass prediction of a disease. The terms “predicting” or “prediction” generally refer to an advance declaration, indication or foretelling of a disease or condition in a subject not (yet) having said disease or condition. For example, a prediction of a disease or condition in a subject may indicate a probability, chance or risk that the subject will develop said disease or condition, for example within a certain time period or by a certain age. Said probability, chance or risk may be indicated inter alia as an absolute value, range or statistics, or may be indicated relative to a suitable control subject or subject population (such as, e.g., relative to a general, normal or healthy subject or subject population). Hence, the probability, chance or risk that a subject will develop a disease or condition may be advantageously indicated as increased or decreased, or as fold-increased or fold-decreased relative to a suitable control subject or subject population. As used herein, the term “prediction” of the conditions or diseases as taught herein in a subject may also particularly mean that the subject has a ‘positive’ prediction of such, i.e., that the subject is at risk of having such (e.g., the risk is significantly increased vis-á-vis a control subject or subject population). The term “prediction of no” diseases or conditions as taught herein as described herein in a subject may particularly mean that the subject has a ‘negative’ prediction of such, i.e., that the subject's risk of having such is not significantly increased vis-á-vis a control subject or subject population.

Suitably, an altered quantity or phenotype of the immune cells in the subject compared to a control subject having normal immune status or not having a disease comprising an immune component indicates that the subject has an impaired immune status or has a disease comprising an immune component or would benefit from an immune therapy.

Hence, the methods may rely on comparing the quantity of immune cell populations, biomarkers, or gene or gene product signatures measured in samples from patients with reference values, wherein said reference values represent known predictions, diagnoses and/or prognoses of diseases or conditions as taught herein.

For example, distinct reference values may represent the prediction of a risk (e.g., an abnormally elevated risk) of having a given disease or condition as taught herein vs. the prediction of no or normal risk of having said disease or condition. In another example, distinct reference values may represent predictions of differing degrees of risk of having such disease or condition.

In a further example, distinct reference values can represent the diagnosis of a given disease or condition as taught herein vs. the diagnosis of no such disease or condition (such as, e.g., the diagnosis of healthy, or recovered from said disease or condition, etc.). In another example, distinct reference values may represent the diagnosis of such disease or condition of varying severity.

In yet another example, distinct reference values may represent a good prognosis for a given disease or condition as taught herein vs. a poor prognosis for said disease or condition. In a further example, distinct reference values may represent varyingly favourable or unfavourable prognoses for such disease or condition.

Such comparison may generally include any means to determine the presence or absence of at least one difference and optionally of the size of such difference between values being compared. A comparison may include a visual inspection, an arithmetical or statistical comparison of measurements. Such statistical comparisons include, but are not limited to, applying a rule.

Reference values may be established according to known procedures previously employed for other cell populations, biomarkers and gene or gene product signatures. For example, a reference value may be established in an individual or a population of individuals characterised by a particular diagnosis, prediction and/or prognosis of said disease or condition (i.e., for whom said diagnosis, prediction and/or prognosis of the disease or condition holds true). Such population may comprise without limitation 2 or more, 10 or more, 100 or more, or even several hundred or more individuals.

A “deviation” of a first value from a second value may generally encompass any direction (e.g., increase: first value>second value; or decrease: first value<second value) and any extent of alteration.

For example, a deviation may encompass a decrease in a first value by, without limitation, at least about 10% (about 0.9-fold or less), or by at least about 20% (about 0.8-fold or less), or by at least about 30% (about 0.7-fold or less), or by at least about 40% (about 0.6-fold or less), or by at least about 50% (about 0.5-fold or less), or by at least about 60% (about 0.4-fold or less), or by at least about 70% (about 0.3-fold or less), or by at least about 80% (about 0.2-fold or less), or by at least about 90% (about 0.1-fold or less), relative to a second value with which a comparison is being made.

For example, a deviation may encompass an increase of a first value by, without limitation, at least about 10% (about 1.1-fold or more), or by at least about 20% (about 1.2-fold or more), or by at least about 30% (about 1.3-fold or more), or by at least about 40% (about 1.4-fold or more), or by at least about 50% (about 1.5-fold or more), or by at least about 60% (about 1.6-fold or more), or by at least about 70% (about 1.7-fold or more), or by at least about 80% (about 1.8-fold or more), or by at least about 90% (about 1.9-fold or more), or by at least about 100% (about 2-fold or more), or by at least about 150% (about 2.5-fold or more), or by at least about 200% (about 3-fold or more), or by at least about 500% (about 6-fold or more), or by at least about 700% (about 8-fold or more), or like, relative to a second value with which a comparison is being made.

Preferably, a deviation may refer to a statistically significant observed alteration. For example, a deviation may refer to an observed alteration which falls outside of error margins of reference values in a given population (as expressed, for example, by standard deviation or standard error, or by a predetermined multiple thereof, e.g., ±1×SD or ±2×SD or ±3×SD, or ±1×SE or ±2×SE or ±3×SE). Deviation may also refer to a value falling outside of a reference range defined by values in a given population (for example, outside of a range which comprises ≥40%, ≥50%, ≥60%, ≥70%, ≥75% or ≥80% or ≥85% or ≥90% or ≥95% or even ≥100% of values in said population).

In a further embodiment, a deviation may be concluded if an observed alteration is beyond a given threshold or cut-off. Such threshold or cut-off may be selected as generally known in the art to provide for a chosen sensitivity and/or specificity of the prediction methods, e.g., sensitivity and/or specificity of at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 85%, or at least 90%, or at least 95%.

For example, receiver-operating characteristic (ROC) curve analysis can be used to select an optimal cut-off value of the quantity of a given immune cell population, biomarker or gene or gene product signatures, for clinical use of the present diagnostic tests, based on acceptable sensitivity and specificity, or related performance measures which are well-known per se, such as positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), Youden index, or similar.

In one embodiment, the signature genes, biomarkers, and/or cells may be detected or isolated by immunofluorescence, immunohistochemistry (IHC), fluorescence activated cell sorting (FACS), mass spectrometry (MS), mass cytometry (CyTOF), RNA-seq, single cell RNA-seq (described further herein), quantitative RT-PCR, single cell qPCR, FISH, RNA-FISH, MERFISH (multiplex (in situ) RNA FISH) and/or by in situ hybridization. Other methods including absorbance assays and colorimetric assays are known in the art and may be used herein. detection may comprise primers and/or probes or fluorescently bar-coded oligonucleotide probes for hybridization to RNA (see e.g., Geiss G K, et al., Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008 March; 26(3):317-25).

In certain embodiments, diseases related to ILC2 responses as described further herein are diagnosed, prognosed, or monitored. For example, a tissue sample may be obtained and analyzed for specific cell markers (IHC) or specific transcripts (e.g., RNA-FISH). Tissue samples for diagnosis, prognosis or detecting may be obtained by endoscopy. In one embodiment, a sample may be obtained by endoscopy and analyzed b FACS. As used herein, “endoscopy” refers to a procedure that uses an endoscope to examine the interior of a hollow organ or cavity of the body. The endoscope may include a camera and a light source. The endoscope may include tools for dissection or for obtaining a biological sample. A cutting tool can be attached to the end of the endoscope, and the apparatus can then be used to perform surgery. Applications of endoscopy that can be used with the present invention include, but are not limited to examination of the oesophagus, stomach and duodenum (esophagogastroduodenoscopy); small intestine (enteroscopy); large intestine/colon (colonoscopy, sigmoidoscopy); bile duct; rectum (rectoscopy) and anus (anoscopy), both also referred to as (proctoscopy); respiratory tract; nose (rhinoscopy); lower respiratory tract (bronchoscopy); ear (otoscope); urinary tract (cystoscopy); female reproductive system (gynoscopy); cervix (colposcopy); uterus (hysteroscopy); fallopian tubes (falloposcopy); normally closed body cavities (through a small incision); abdominal or pelvic cavity (laparoscopy); interior of a joint (arthroscopy); or organs of the chest (thoracoscopy and mediastinoscopy).

In certain embodiments, the method provides for treating a patient with CGRP, wherein the patient is suffering from a disease related to ILC2 inflammatory responses (e.g., allergy), the method comprising the steps of determining whether the patient expresses a gene signature, biological program or marker gene as described herein; obtaining or having obtained a biological sample from the patient; and performing or having performed an assay as described herein on the biological sample to determine if the patient expresses the gene signature, biological program or marker gene; and if the patient has an ILC2 inflammatory gene signature, biological program or marker gene, then administering CGRP to the patient in an amount sufficient to shift the phenotype to a homeostatic phenotype, and if the patient does not have an ILC2 inflammatory gene signature, biological program or marker gene, then not administering CGRP to the patient, wherein a risk of having inflammatory symptoms is increased if the patient has an ILC2 inflammatory gene signature, biological program or marker gene.

The present invention also may comprise a kit with a detection reagent that binds to one or more biomarkers or can be used to detect one or more biomarkers.

Methods of Quantitating a Type 2 Immune Response

In certain embodiments, a method of quantitating a type 2 immune response comprises determining the ILC2 frequency, wherein increased frequency of ILC2s as compared to a control frequency is associated with an increased type 2 immune response. As used herein, “frequency” refers to the rate of cells in a given sample. For example, frequency=the number of a cell type divided by the total number of all cell types in a sample. In certain embodiments, flow cytometry techniques are used to determine the frequency (e.g., FACS). The frequency may be in relation to all cells, all immune cells or all ILC cells in a population of cells obtained from a subject. In certain embodiments, the method further comprises determining the frequency of one or more cells selected from the group consisting of: mast cells, macrophages, neutrophils, and CD11b+CD103+ dendritic cells, wherein increased frequency of mast cells, macrophages and/or neutrophils, and/or decreased frequency of CD11b+CD103+ dendritic cells as compared to a control frequency is associated with an increased type 2 immune response. The frequency may be in relation to all cells, all immune cells or all ILC cells in a population of cells obtained from a subject. In certain embodiments, the method is a diagnostic method for determining an immune response in a subject in need thereof. In certain embodiments, a subject is monitored during treatment of an aberrant immune response.

In certain embodiments, a method of quantitating a type 2 immune response comprises determining the expression of one or more genes selected from Table 3 or determining the frequency of the cell types expressing the one or more genes selected from Table 3, wherein changes in expression or frequency according to Table 3 is associated with an increased type 2 immune response.

In certain embodiments, the method comprises determining expression of one or more genes selected from Srgn, Hes1, Sla, Ppp1r15a, Furin, Actg1, Il13, Hspa8, Lilr4b, 4930523C07Rik and Dnaja1 in LP cluster 12.

In certain embodiments, the method comprises determining expression of one or more genes selected from Sla, Jund, Klf4 and Dusp1 in LP cluster 15.

In certain embodiments, the method comprises determining expression of one or more genes selected from Txnip, Mcpt1, Igkv1-135, Mcpt2, Ighg1, Igkv12-44, Ifi2712a, Ubald2, Cacna1s, Sepp1, Pdia6, Rilpl2, Iglc2, Dusp5, Fosb, Serp1, Grasp, Ccr10, Ddit4, Malat1, Pim1, Hsp90b1, Trf, Ifi27, Odd and Xbp1 in LP cluster 20.

In certain embodiments, the method comprises determining expression of one or more genes selected from Btg2, Junb, Ubb, Dusp1, Bcl2, Pnrc1, Pim1, Jund, Actg1, Btg1 and Irf7 in LP cluster 3.

In certain embodiments, the method comprises determining expression of one or more genes selected from Jun, Zfp3612, Fos, Neat1 and Irf7 in LP cluster 6.

In certain embodiments, the method comprises determining expression of one or more genes selected from Tsc22d3, Wdr89, Txnip, Uba52, Ddit4, Bcl2, Cd74 and Jund in PP cluster 1.

In certain embodiments, the method comprises determining expression of one or more genes selected from Zfp3612, Tsc22d3 in PP cluster 2.

In certain embodiments, the method comprises determining expression of one or more genes selected from Jund, Id2, Pim1, Nfkbia, Klf4, Tgif1, Hk2, Junb, Gimap1 and Dusp5 in PP cluster 3.

In certain embodiments, the method comprises determining expression of one or more genes selected from Jund, Klf4, Junb, Lmna, Ncoa7, Dusp1 and Pim1 in PP cluster 4.

In certain embodiments, the method comprises determining expression of one or more genes selected from Tsc22d3 in PP cluster 5.

In certain embodiments, the method comprises determining expression of one or more genes selected from Mcpt1 and Defa24 in PP cluster 6.

In certain embodiments, the method comprises determining expression of one or more genes selected from Jund in PP cluster 8.

In certain embodiments, the method comprises determining expression of one or more genes selected from Igha in PP cluster 9.

MS Methods

Biomarker detection may also be evaluated using mass spectrometry methods. A variety of configurations of mass spectrometers can be used to detect biomarker values. Several types of mass spectrometers are available or can be produced with various configurations. In general, a mass spectrometer has the following major components: a sample inlet, an ion source, a mass analyzer, a detector, a vacuum system, and instrument-control system, and a data system. Difference in the sample inlet, ion source, and mass analyzer generally define the type of instrument and its capabilities. For example, an inlet can be a capillary-column liquid chromatography source or can be a direct probe or stage such as used in matrix-assisted laser desorption. Common ion sources are, for example, electrospray, including nanospray and microspray or matrix-assisted laser desorption. Common mass analyzers include a quadrupole mass filter, ion trap mass analyzer and time-of-flight mass analyzer. Additional mass spectrometry methods are well known in the art (see Burlingame et al., Anal. Chem. 70:647 R-716R (1998); Kinter and Sherman, New York (2000)).

Protein biomarkers and biomarker values can be detected and measured by any of the following: electrospray ionization mass spectrometry (ESI-MS), ESI-MS/MS, ESI-MS/(MS)n, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), desorption/ionization on silicon (DIOS), secondary ion mass spectrometry (SIMS), quadrupole time-of-flight (Q-TOF), tandem time-of-flight (TOF/TOF) technology, called ultraflex III

TOF/TOF, atmospheric pressure chemical ionization mass spectrometry (APCI-MS), APCI-MS/MS, APCI-(MS).sup.N, atmospheric pressure photoionization mass spectrometry (APPI-MS), APPI-MS/MS, and APPI-(MS).sup.N, quadrupole mass spectrometry, Fourier transform mass spectrometry (FTMS), quantitative mass spectrometry, and ion trap mass spectrometry.

Sample preparation strategies are used to label and enrich samples before mass spectroscopic characterization of protein biomarkers and determination biomarker values. Labeling methods include but are not limited to isobaric tag for relative and absolute quantitation (iTRAQ) and stable isotope labeling with amino acids in cell culture (SILAC). Capture reagents used to selectively enrich samples for candidate biomarker proteins prior to mass spectroscopic analysis include but are not limited to aptamers, antibodies, nucleic acid probes, chimeras, small molecules, an F(ab′)₂fragment, a single chain antibody fragment, an Fv fragment, a single chain Fv fragment, a nucleic acid, a lectin, a ligand-binding receptor, affybodies, nanobodies, ankyrins, domain antibodies, alternative antibody scaffolds (e.g. diabodies etc) imprinted polymers, avimers, peptidomimetics, peptoids, peptide nucleic acids, threose nucleic acid, a hormone receptor, a cytokine receptor, and synthetic receptors, and modifications and fragments of these.

Immunoassays

Immunoassay methods are based on the reaction of an antibody to its corresponding target or analyte and can detect the analyte in a sample depending on the specific assay format. To improve specificity and sensitivity of an assay method based on immunoreactivity, monoclonal antibodies are often used because of their specific epitope recognition. Polyclonal antibodies have also been successfully used in various immunoassays because of their increased affinity for the target as compared to monoclonal antibodies Immunoassays have been designed for use with a wide range of biological sample matrices Immunoassay formats have been designed to provide qualitative, semi-quantitative, and quantitative results.

Quantitative results may be generated through the use of a standard curve created with known concentrations of the specific analyte to be detected. The response or signal from an unknown sample is plotted onto the standard curve, and a quantity or value corresponding to the target in the unknown sample is established.

Numerous immunoassay formats have been designed. ELISA or EIA can be quantitative for the detection of an analyte/biomarker. This method relies on attachment of a label to either the analyte or the antibody and the label component includes, either directly or indirectly, an enzyme. ELISA tests may be formatted for direct, indirect, competitive, or sandwich detection of the analyte. Other methods rely on labels such as, for example, radioisotopes (I¹²⁵) or fluorescence. Additional techniques include, for example, agglutination, nephelometry, turbidimetry, Western blot, immunoprecipitation, immunocytochemistry, immunohistochemistry, flow cytometry, Luminex assay, and others (see ImmunoAssay: A Practical Guide, edited by Brian Law, published by Taylor & Francis, Ltd., 2005 edition).

Exemplary assay formats include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, fluorescent, chemiluminescence, and fluorescence resonance energy transfer (FRET) or time resolved-FRET (TR-FRET) immunoassays. Examples of procedures for detecting biomarkers include biomarker immunoprecipitation followed by quantitative methods that allow size and peptide level discrimination, such as gel electrophoresis, capillary electrophoresis, planar electrochromatography, and the like.

Methods of detecting and/or quantifying a detectable label or signal generating material depend on the nature of the label. The products of reactions catalyzed by appropriate enzymes (where the detectable label is an enzyme; see above) can be, without limitation, fluorescent, luminescent, or radioactive or they may absorb visible or ultraviolet light. Examples of detectors suitable for detecting such detectable labels include, without limitation, x-ray film, radioactivity counters, scintillation counters, spectrophotometers, colorimeters, fluorometers, luminometers, and densitometers.

Any of the methods for detection can be performed in any format that allows for any suitable preparation, processing, and analysis of the reactions. This can be, for example, in multi-well assay plates (e.g., 96 wells or 384 wells) or using any suitable array or microarray. Stock solutions for various agents can be made manually or robotically, and all subsequent pipetting, diluting, mixing, distribution, washing, incubating, sample readout, data collection and analysis can be done robotically using commercially available analysis software, robotics, and detection instrumentation capable of detecting a detectable label.

Hybridization Assays

Such applications are hybridization assays in which a nucleic acid that displays “probe” nucleic acids for each of the genes to be assayed/profiled in the profile to be generated is employed.

In these assays, a sample of target nucleic acids is first prepared from the initial nucleic acid sample being assayed, where preparation may include labeling of the target nucleic acids with a label, e.g., a member of a signal producing system. Following target nucleic acid sample preparation, the sample is contacted with the array under hybridization conditions, whereby complexes are formed between target nucleic acids that are complementary to probe sequences attached to the array surface. The presence of hybridized complexes is then detected, either qualitatively or quantitatively. Specific hybridization technology which may be practiced to generate the expression profiles employed in the subject methods includes the technology described in U.S. Pat. Nos. 5,143,854; 5,288,644; 5,324,633; 5,432,049; 5,470,710; 5,492,806; 5,503,980; 5,510,270; 5,525,464; 5,547,839; 5,580,732; 5,661,028; 5,800,992, the disclosures of which are herein incorporated by reference, as well as International Patent Publication Nos. WO 95/21265, WO 96/31622, WO 97/10365, and WO 97/27317; European Patent Application Nos. EP 373203; and EP 785280. In these methods, an array of “probe” nucleic acids that includes a probe for each of the biomarkers whose expression is being assayed is contacted with target nucleic acids as described above. Contact is carried out under hybridization conditions, e.g., stringent hybridization conditions as described above, and unbound nucleic acid is then removed. The resultant pattern of hybridized nucleic acids provides information regarding expression for each of the biomarkers that have been probed, where the expression information is in terms of whether or not the gene is expressed and, typically, at what level, where the expression data, i.e., expression profile, may be both qualitative and quantitative.

Optimal hybridization conditions will depend on the length (e.g., oligomer vs. polynucleotide greater than 200 bases) and type (e.g., RNA, DNA, PNA) of labeled probe and immobilized polynucleotide or oligonucleotide. General parameters for specific (i.e., stringent) hybridization conditions for nucleic acids are described in Sambrook et al., supra, and in Ausubel et al., “Current Protocols in Molecular Biology”, Greene Publishing and Wiley-interscience, NY (1987), which is incorporated in its entirety for all purposes. When the cDNA microarrays are used, typical hybridization conditions are hybridization in 5×SSC plus 0.2% SDS at 65 C for 4 hours followed by washes at 25° C. in low stringency wash buffer (1×SSC plus 0.2% SDS) followed by 10 minutes at 25° C. in high stringency wash buffer (0.1SSC plus 0.2% SDS) (see Shena et al., Proc. Natl. Acad. Sci. USA, Vol. 93, p. 10614 (1996)). Useful hybridization conditions are also provided in, e.g., Tijessen, Hybridization With Nucleic Acid Probes”, Elsevier Science Publishers B.V. (1993) and Kricka, “Nonisotopic DNA Probe Techniques”, Academic Press, San Diego, Calif. (1992).

Sequencing and Single Cell Sequencing

In certain embodiments, the invention involves targeted nucleic acid profiling (e.g., sequencing, quantitative reverse transcription polymerase chain reaction, and the like) (see e.g., Geiss G K, et al., Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008 March; 26(3):317-25). In certain embodiments, a target nucleic acid molecule (e.g., RNA molecule), may be sequenced by any method known in the art, for example, methods of high-throughput sequencing, also known as next generation sequencing or deep sequencing. A nucleic acid target molecule labeled with a barcode (for example, an origin-specific barcode) can be sequenced with the barcode to produce a single read and/or contig containing the sequence, or portions thereof, of both the target molecule and the barcode. Exemplary next generation sequencing technologies include, for example, Illumina sequencing, Ion Torrent sequencing, 454 sequencing, SOLiD sequencing, and nanopore sequencing amongst others.

In certain embodiments, the invention involves single cell RNA sequencing (see, e.g., Kalisky, T., Blainey, P. & Quake, S. R. Genomic Analysis at the Single-Cell Level. Annual review of genetics 45, 431-445, (2011); Kalisky, T. & Quake, S. R. Single-cell genomics. Nature Methods 8, 311-314 (2011); Islam, S. et al. Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Research, (2011); Tang, F. et al. RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nature Protocols 5, 516-535, (2010); Tang, F. et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nature Methods 6, 377-382, (2009); Ramskold, D. et al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nature Biotechnology 30, 777-782, (2012); and Hashimshony, T., Wagner, F., Sher, N. & Yanai, I. CEL-Seq: Single-Cell RNA-Seq by Multiplexed Linear Amplification. Cell Reports, Cell Reports, Volume 2, Issue 3, p 666-673, 2012).

In certain embodiments, the invention involves plate based single cell RNA sequencing (see, e.g., Picelli, S. et al., 2014, “Full-length RNA-seq from single cells using Smart-seq2” Nature protocols 9, 171-181, doi:10.1038/nprot.2014.006).

In certain embodiments, the invention involves high-throughput single-cell RNA-seq. In this regard reference is made to Macosko et al., 2015, “Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets” Cell 161, 1202-1214; International patent application number PCT/US2015/049178, published as WO2016/040476 on Mar. 17, 2016; Klein et al., 2015, “Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells” Cell 161, 1187-1201; International patent application number PCT/US2016/027734, published as WO2016168584A1 on Oct. 20, 2016; Zheng, et al., 2016, “Haplotyping germline and cancer genomes with high-throughput linked-read sequencing” Nature Biotechnology 34, 303-311; Zheng, et al., 2017, “Massively parallel digital transcriptional profiling of single cells” Nat. Commun. 8, 14049 doi: 10.1038/ncomms14049; International patent publication number WO2014210353A2; Zilionis, et al., 2017, “Single-cell barcoding and sequencing using droplet microfluidics” Nat Protoc. January; 12(1):44-73; Cao et al., 2017, “Comprehensive single cell transcriptional profiling of a multicellular organism by combinatorial indexing” bioRxiv preprint first posted online Feb. 2, 2017, doi: dx.doi.org/10.1101/104844; Rosenberg et al., 2017, “Scaling single cell transcriptomics through split pool barcoding” bioRxiv preprint first posted online Feb. 2, 2017, doi: dx.doi.org/10.1101/105163; Rosenberg et al., “Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding” Science 15 Mar. 2018; Vitak, et al., “Sequencing thousands of single-cell genomes with combinatorial indexing” Nature Methods, 14(3):302-308, 2017; Cao, et al., Comprehensive single-cell transcriptional profiling of a multicellular organism. Science, 357(6352):661-667, 2017; and Gierahn et al., “Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput” Nature Methods 14, 395-398 (2017), all the contents and disclosure of each of which are herein incorporated by reference in their entirety.

In certain embodiments, the invention involves single nucleus RNA sequencing. In this regard reference is made to Swiech et al., 2014, “In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9” Nature Biotechnology Vol. 33, pp. 102-106; Habib et al., 2016, “Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons” Science, Vol. 353, Issue 6302, pp. 925-928; Habib et al., 2017, “Massively parallel single-nucleus RNA-seq with DroNc-seq” Nat Methods. 2017 October; 14(10):955-958; and International patent application number PCT/US2016/059239, published as WO2017164936 on Sep. 28, 2017, which are herein incorporated by reference in their entirety.

In certain embodiments, the invention involves the Assay for Transposase Accessible Chromatin using sequencing (ATAC-seq) as described. (see, e.g., Buenrostro, et al., Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature methods 2013; 10 (12): 1213-1218; Buenrostro et al., Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486-490 (2015); Cusanovich, D. A., Daza, R., Adey, A., Pliner, H., Christiansen, L., Gunderson, K. L., Steemers, F. J., Trapnell, C. & Shendure, J. Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing. Science. 2015 May 22; 348(6237):910-4. doi: 10.1126/science.aab1601. Epub 2015 May 7; US Patent Publication Nos. US 2016-0208323 A1 and US 2016-0060691A1; and International Patent Publication No. WO 2017/156336A1).

Methods of Screening

A further aspect of the invention relates to a method for identifying an agent capable of modulating one or more phenotypic aspects of a cell or cell population as disclosed herein, comprising: a) applying a candidate agent to the cell or cell population; b) detecting modulation of one or more phenotypic aspects of the cell or cell population by the candidate agent, thereby identifying the agent. The phenotypic aspects of the cell or cell population that is modulated may be a gene signature or biological program specific to a cell type or cell phenotype or phenotype specific to a population of cells (e.g., an ILC2 immune response phenotype). In certain embodiments, steps can include administering candidate modulating agents to cells, detecting identified cell (sub)populations for changes in signatures, or identifying relative changes in cell (sub) populations which may comprise detecting relative abundance of particular gene signatures.

The term “modulate” broadly denotes a qualitative and/or quantitative alteration, change or variation in that which is being modulated. Where modulation can be assessed quantitatively—for example, where modulation comprises or consists of a change in a quantifiable variable such as a quantifiable property of a cell or where a quantifiable variable provides a suitable surrogate for the modulation—modulation specifically encompasses both increase (e.g., activation) or decrease (e.g., inhibition) in the measured variable. The term encompasses any extent of such modulation, e.g., any extent of such increase or decrease, and may more particularly refer to statistically significant increase or decrease in the measured variable. By means of example, modulation may encompass an increase in the value of the measured variable by at least about 10%, e.g., by at least about 20%, preferably by at least about 30%, e.g., by at least about 40%, more preferably by at least about 50%, e.g., by at least about 75%, even more preferably by at least about 100%, e.g., by at least about 150%, 200%, 250%, 300%, 400% or by at least about 500%, compared to a reference situation without said modulation; or modulation may encompass a decrease or reduction in the value of the measured variable by at least about 10%, e.g., by at least about 20%, by at least about 30%, e.g., by at least about 40%, by at least about 50%, e.g., by at least about 60%, by at least about 70%, e.g., by at least about 80%, by at least about 90%, e.g., by at least about 95%, such as by at least about 96%, 97%, 98%, 99% or even by 100%, compared to a reference situation without said modulation. Preferably, modulation may be specific or selective, hence, one or more desired phenotypic aspects of an immune cell or immune cell population may be modulated without substantially altering other (unintended, undesired) phenotypic aspect(s).

The term “agent” broadly encompasses any condition, substance or agent capable of modulating one or more phenotypic aspects of a cell or cell population as disclosed herein. Such conditions, substances or agents may be of physical, chemical, biochemical and/or biological nature. The term “candidate agent” refers to any condition, substance or agent that is being examined for the ability to modulate one or more phenotypic aspects of a cell or cell population as disclosed herein in a method comprising applying the candidate agent to the cell or cell population (e.g., exposing the cell or cell population to the candidate agent or contacting the cell or cell population with the candidate agent) and observing whether the desired modulation takes place.

Agents may include any potential class of biologically active conditions, substances or agents, such as for instance antibodies, proteins, peptides, nucleic acids, oligonucleotides, small molecules, or combinations thereof, as described herein.

The methods of phenotypic analysis can be utilized for evaluating environmental stress and/or state, for screening of chemical libraries, and to screen or identify structural, synthetic, genomic, and/or organism and species variations. For example, a culture of cells, can be exposed to an environmental stress, such as but not limited to heat shock, osmolarity, hypoxia, cold, oxidative stress, radiation, starvation, a chemical (for example a therapeutic agent or potential therapeutic agent) and the like. After the stress is applied, a representative sample can be subjected to analysis, for example at various time points, and compared to a control, such as a sample from an organism or cell, for example a cell from an organism, or a standard value. By exposing cells, or fractions thereof, tissues, or even whole animals, to different members of the chemical libraries, and performing the methods described herein, different members of a chemical library can be screened for their effect on immune phenotypes thereof simultaneously in a relatively short amount of time, for example using a high throughput method.

Aspects of the present disclosure relate to the correlation of an agent with the spatial proximity and/or epigenetic profile of the nucleic acids in a sample of cells. In some embodiments, the disclosed methods can be used to screen chemical libraries for agents that modulate chromatin architecture epigenetic profiles, and/or relationships thereof.

In some embodiments, screening of test agents involves testing a combinatorial library containing a large number of potential modulator compounds. A combinatorial chemical library may be a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis, by combining a number of chemical “building blocks” such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide library, is formed by combining a set of chemical building blocks (amino acids) in every possible way for a given compound length (for example the number of amino acids in a polypeptide compound). Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks.

In certain embodiments, the present invention provides for gene signature screening. The concept of signature screening was introduced by Stegmaier et al. (Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation. Nature Genet. 36, 257-263 (2004)), who realized that if a gene-expression signature was the proxy for a phenotype of interest, it could be used to find small molecules that effect that phenotype without knowledge of a validated drug target. The signatures or biological programs of the present invention may be used to screen for drugs that reduce the signature or biological program in cells as described herein. The signature or biological program may be used for GE-HTS. In certain embodiments, pharmacological screens may be used to identify drugs that are selectively toxic to cells having a signature.

The Connectivity Map (cmap) is a collection of genome-wide transcriptional expression data from cultured human cells treated with bioactive small molecules and simple pattern-matching algorithms that together enable the discovery of functional connections between drugs, genes and diseases through the transitory feature of common gene-expression changes (see, Lamb et al., The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease. Science 29 Sep. 2006: Vol. 313, Issue 5795, pp. 1929-1935, DOI: 10.1126/science.1132939; and Lamb, J., The Connectivity Map: a new tool for biomedical research. Nature Reviews Cancer January 2007: Vol. 7, pp. 54-60). In certain embodiments, Cmap can be used to screen for small molecules capable of modulating a signature or biological program of the present invention in silico.

The invention is further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES
Example 1—an Atlas of Mouse Small Intestinal Immune Cells at Homeostasis and in Type 2 Inflammation

To comprehensively characterize small intestinal immune cells, Applicants generated scRNA-Seq profiles for 58,067 immune cells collected from lamina propria (LP) and Peyer's patch (PP) regions at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA) (Brandt et al., 2003) (FIGS. 1A and 8A). To ensure sufficient representation of rare cells, Applicants combined a normalization strategy—removing by flow sorting either a portion of IgD+ naïve B cells, which are the most abundant cell type in PPs, or all CD19+ and CD3+ T cells (FIG. 8B, Methods)—with profiling of a sufficiently large number of cells number (P>0.99 to recover at least 15 cells from each cluster, Methods) by massively parallel scRNA-seq (Haber et al., 2017) (Methods). Applicants obtained 36,797 and 21,270 high quality cells passing initial filtering (Methods) from PP and LP regions, respectively.

Overall, Applicants annotated 27 cell subsets across the two compartments, spanning T cells, B cells, ILCs, dendritic cells (DCs), myeloid cells and stromal cells, in frequencies ranging from 0.07% to 14%. Briefly, Applicants first partitioned the cells from the PP regions by unsupervised clustering (Methods) into 46 clusters, retained the 97% of cells that were robustly assigned cell identities in each cluster (Methods), assigned the cells from the LP regions to the 46 clusters using a classifier (Methods), and visualized the data with scvis (Ding et al., 2018), a deep generative model-based method (FIGS. 1B and 8C, Methods). Next, Applicants identified genes that were differentially expressed between the cells in each cluster and the remaining cells (Table 1, Methods), as well as between pairs of clusters (Table 2), to elucidate identities of similar cell types/states. Applicants excluded from downstream analysis clusters mostly consisting of contaminants from epithelium, likely doublets, or cells with a small number of Unique Molecular Identifiers (UMIs) (FIGS. 1C and 8D), or lacking distinct markers (Methods). Altogether, Applicants retained 27 clusters spanning 85% of the cells and each associated with distinct marker genes (FIG. 8E, Methods).

Importantly, known distinct cell types with highly similar expression profiles were correctly distinguished by the analysis. For example, NKp46+ILC3s and CCR6+ lymphoid tissue inducer (LTi) cells were recovered as separate clusters, even though they both require RORγt controlled expression programs for their fate determination (Robinette et al., 2015). Nevertheless, LTi cells were distinguished by significantly higher expression levels of MHCII antigen presentation modules (FIG. 8F, adjusted P<0.05, likelihood ratio test), whose expression on ILCs has been shown to regulate intestinal homeostasis (Hepworth et al., 2013).

The atlas highlighted expected differences in cellular composition between the LP and PP regions (FIGS. 1D and 8G). For example, resting and IgD⁻GL7⁺ germinal center (GC) B cells were exclusively found in PPs (FIG. 8G). Conversely, although CD138⁺ antibody producing plasma cells differentiate from GC B cells, they were predominantly found in LP samples (FIG. 8G) and confirmed in LP regions in situ (FIG. 8H), highlighting their potential requirement for antibody secretion adjacent to microbes and other antigens in the intestinal mucosa. In another example, LTi cells were significantly enriched (adjusted P=4.75*10⁻³, Wald test) in PP vs. LP regions (FIG. 1D), which Applicants confirmed by flow cytometry (FIG. 1E, P<0.001, Fisher's exact test). The LTi cell distribution is consistent with their critical function in supporting lymphoid tissue development. ILC1s and Natural Killer (NK) cells were also significantly enriched in PP regions (FIG. 1D, adjusted P=4.29*10⁻⁷and P=1.19*10⁻¹⁷, respectively, Wald test), suggesting they have unique functions in PPs. Indeed, NK cells suppress affinity maturation of GC B cells (Rydyznski et al., 2018), which probably requires their localization in B cell follicles.

Example 2—Increase in ILC2 Proportions and Changes in their Expression Programs are Prominent Features of OVA-Induced Type 2 Inflammation

Cell composition was remodeled in type 2 inflammation (FIGS. 2A, B and 9A), highlighting both known and unique responses. Mast cell expansion, a well-established feature of allergic reactions (Brandt et al., 2003), was observed in OVA-treated mice (adjusted P=1.03*10⁻¹¹, Wald test, FIG. 2B) and validated by flow cytometry (FIG. 2C, P=0.005, t-test). Applicants also observed a significant increase in ILC2 frequency in mice with type 2 immune reactions to OVA (FIG. 2B, P=1.22*10⁻², Wald test), which Applicants validated by flow cytometry (FIG. 2D, P=0.009, t-test), highlighting their importance in this allergic inflammatory model (Burton et al., 2018). Macrophage and neutrophil frequencies also increased significantly in OVA-treated mice (P=3.87*10⁻³and P=4.15*10⁻³, respectively, Wald test), reflecting immune cell infiltration. CD11b⁺CD103⁺ DCs, one of four different populations of DCs in the intestine (Mowat and Agace, 2014), were the most significantly reduced by OVA-induced inflammation (P=6.04*10⁻⁸, Wald test), suggesting that they were likely involved in the maintenance of gut homeostasis, and suppressed in the type 2 inflammatory condition.

The impact of type 2 inflammation on cell intrinsic expression changes was primarily centered in mast cells and ILC2s in both LP and PP regions (FIG. 2E and Table 3). Genes associated with cell type-specific activation were induced in mast cells (e.g., Mcpt1, Mcpt4) and ILC2s (e.g., Il13, Il4) (FIG. 9B), suggesting an activation phenotype in both cell types. In addition, Ighg1 and Ighe expression in plasma cells was significantly increased (P=1.45*10⁻¹⁰⁷and 2.86*10⁻¹³, respectively; likelihood ratio test) after the induction of allergic inflammation (FIG. 9C), consistent with the fact that IL-4 induces class-switch recombination of immunoglobulin heavy (Ig) chain towards IgG1 and IgE (Manis et al., 2002). Additionally, genes involved in the type 1 interferon pathway, such as Irf1 and Isg15 in macrophages and Ifnar1 and Ifitm3 in plasma cells, were suppressed during type 2 inflammation (FIG. 9B), providing potential mechanistic explanations for the dampened antiviral immunity in allergic inflammation (Kloepfer et al., 2012; Rowe and Gill, 2015).

Example 3—Topic Models Identify Cell Type-Specific Programs that are Increased with Inflammation in Mast Cells, ILC2s, Th2 Cells and Fibroblast Subsets

To identify more nuanced changes in expression programs in response to type 2 inflammation, Applicants relied on topic modeling using Latent Dirichlet Allocations (Blei et al., 2003), which has recently been applied to scRNA-seq data (Bielecki et al., 2018; duVerle et al., 2016). Originally developed to discover key semantic topics reflected by the words used in a corpus of documents (Dumais et al., 1990), topic modeling can be used to explore gene programs (“topics”) in each cell (“document”) based on the distribution of genes (“words”) expressed in the cell. A gene can belong to multiple programs, and its relative relevance in the topic is reflected by a weight. A cell is then represented as a weighted mixture of topics, where the weights reflect the importance of the corresponding gene program in the cell. Applicants learned topic models for each cell lineage or group separately, and then searched for topics that were differentially weighted between homeostasis and inflammation in cells of the same type (Methods, Table 4, FIGS. 3A-E and 10A-F).

Topics specifically characterizing activation in mast cells and ILC2s increased in prominence following inflammation. Topic 1 (“mast cell activation program”), which was heavily weighted in the mast cell cluster among myeloid cells, was characterized by Cpa3 and Mcpt4 expression and significantly more prominent in mast cells from mice treated with OVA than controls (adjusted P=2.84*10⁻⁶⁷, Mann-Whitney U test, FIG. 3A). Topic 2 (“ILC2 activation program”), which was heavily weighted in the ILC2 cluster, included type 2 genes such as Il13 and Il4. Topic 2 was significantly more prominent in ILC2s after induction of inflammation (adjusted P=8.01*10⁻¹², Mann-Whitney U test, FIG. 3B). Consistent with the differential expression analysis, these two topics captured the major events induced by inflammation.

Programs related to inflammatory responses were also more heavily weighted in Th2 cells under inflammatory conditions, whereas those related to T regulatory cells were unchanged between inflammation and homeostasis. Specifically, topic 5 (“Th2 inflammatory program”), consisting of type 2 inflammatory genes, including Il13, Gata3, 116, Areg and Il1rl1, was present only in a subset of cells from the activated CD4⁺ T cell cluster that were likely type 2 T helper (TH2) cells (FIG. 3C). Topic 5 weights were significantly higher in cells from OVAtreated mice than from controls (adjusted P=2.73*10⁻⁵, Mann-Whitney U test, FIG. 3C). Topic 9 (“T regulatory program”), comprised of Foxp3, Lag3, Il10 and other Th regulatory genes, was present in a different subset of CD4⁺ T cells (FIG. 3D), but its weight showed only a minor change with inflammation (adjusted P=0.002, Mann-Whitney U test, FIG. 3D). This suggests that activation of type 2 inflammation in this model did not significantly interfere with the activity of regulatory T cells.

Topic 4 from stromal cells, defined by the expression of the type 2 inflammatory cytokine 1133 and key chemokines such as Ccl21a, was uniquely associated with fibroblasts and increased in weight with inflammation (FIG. 3E, adjusted P=2.69*10⁻⁵, Mann-Whitney U test). Applicants confirmed that IL-33 and CCL21 were co-expressed in PDPN⁺ stromal cells by immunofluorescence (FIG. 10G). Moreover, the number of IL-33⁺PDPN⁺intestinal fibroblasts was significantly increased in mice under type 2 inflammation induced by OVA (FIG. 3F, P=0.002, t-test), indicating that stromal cell-derived IL-33 may play critical roles in promoting intestinal type 2 inflammation.

Example 4—Calca-Encoded α-CGRP Expression is a Key Feature of the ILC2 Activation Program Induced by Inflammation, but its Receptor is Repressed by Inflammation

Calca was the highest and most uniquely scoring gene in the ILC2 activation program (FIG. 3B) and Calca transcript levels were highest in ILC2s among all cell types in the dataset (FIGS. 4A and 11A). Exons 4 and 5 of Calca encode the neuropeptides calcitonin (CT) and α-CGRP, respectively, via alternative splicing (Amara et al., 1982). Quantitative PCR (qPCR) revealed that while CT-encoding exon 4 was expressed in intestinal KLRG1⁺ILC2s at steady state (FIG. 11B), α-CGRP-encoding exon 5 was detectable only following induction of a type 2 inflammatory reaction to OVA (P=0.01, t-test) (FIG. 4B). Conversely, the corresponding transcripts of α-CGRP receptor components—a G-protein-coupled receptor complex consisting of CRLR and RAMP1—were expressed in ILC2s at steady state (FIGS. 4B and 11A), but significantly repressed by type 2 inflammation (FIG. 4B, P=0.005 and 0.02 for Calcrl and Ramp 1, respectively, t-test). The Calcr transcript, encoding the CT receptor, was not detectable by either scRNA-seq or qPCR (data not shown). Taken together, these results are consistent with a negative feedback model, where signaling through α-CGRP to ILC2s suppresses its receptor's expression in the cells, and suggest that an α-CGRP-mediated signaling pathway may regulate ILC2 activity in type 2 immune responses.

Example 5—α-CGRP Suppresses Type 2 Inflammation-Induced Activation and Expansion of ILC2s In Vitro and In Vivo

To determine if α-CGRP can directly trigger signaling in ILC2s and impact their transcriptional states under inflammatory conditions, Applicants performed bulk RNA-seq of KLRG1⁺ ILC2s isolated from the small intestine and stimulated in vitro with IL-25 alone or together with α-CGRP. As expected, IL-25 alone induced the expected activation phenotype, including expression of type 2 cytokines, such as Il13 and Il5, and key mitotic genes, such as Myc (FIG. 4C). Strikingly, this IL-25-induced activation signature was significantly suppressed when cells were treated with both IL-25 and α-CGRP (FIG. 4C,D, adjusted P<0.001, t-test), with the exception of a few genes, notably Il5, which was further induced (FIGS. 4C and 11C). Moreover, α-CGRP co-treatment significantly suppressed IL-25-induced cell division (FIG. 4E, P=0.01, t-test). Thus, α-CGRP inhibits IL-25-induced proliferation and activation of intestinal KLRG1+ILC2s.

Applicants next used an IL-25-induced in vivo activation model (Huang et al., 2015) (FIG. 5A) to show that α-CGRP suppresses expansion of ILC2s responding to inflammation. Intraperitoneal administration of α-CGRP impaired IL-25-induced expansion of KLRG1⁺ ILC2s (FIGS. 5B and 12A), consistent with the in vitro results. Recent work has shown that intestinal KLRG1⁺ ILC2s can migrate to mesenteric lymph nodes (mLNs) and other tissues during inflammation via sphingosine 1-phosphate (S1P)-mediated chemotaxis (Huang et al., 2018). To determine whether α-CGRP primarily impacts intestinal or mLN ILC2s, Applicants relied on the fact that intestinal GATA3⁺ ILC2s are generally phenotypically KLRG1⁺ST2⁻ (data not shown), whereas mLN ILC2s are mainly ST2⁺ at steady state (FIG. 5C). IL-25 administration increased the frequency of both KLRG1⁺ST2⁻ inflammatory ILC2s and ST2⁺ ILC2s in mLNs (FIGS. 5C-E and 12B). But co-administration with α-CGRP only reduced the frequency of KLRG1⁺ST2⁻ILC2s (FIGS. 5C,D and 12B), which are cells that migrated from the small intestine to the mLNs, but not of ST2⁺ ILC2s (FIG. 5E). Thus, α-CGRP preferentially regulates the response of intestinal KLRG1⁺ST2⁻ ILC2s. Furthermore, α-CGRP also significantly suppressed the expansion of intestinal ILC2s in a food allergy model (FIGS. 5F,G and 12C,D, P=0.02 for 5G, P=0.009 for S5D, t-test), where Applicants intragastrically administrated α-CGRP together with OVA into pre-sensitized mice. Taken together, α-CGRP antagonized expansion of intestinal KLRG1⁺ ILC2s in two different type 2 inflammatory models.

Example 6—at Homeostasis, α-CGRP is Predominantly Expressed In Vivo in Two Subsets of Chat⁺ Enteric Neurons

Without inflammation, intestinal KLRG1⁺ ILC2s expressed CGRP receptors (FIG. 4B), but not CGRP, leading us to search for neighboring cell type(s) which potentially produce CGRP at homeostasis. To this end, Applicants analyzed Calca gene expression across multiple intestinal scRNA-seq datasets, including the previous epithelial atlas for the mouse small intestine epithelium (Haber et al., 2017) (FIG. 13A), the intestinal immune atlas here (FIG. 1), and scRNA-Seq of enteric neurons from Wnt1-Cre:R26Tomato mice (Zeisel et al., 2018) (FIGS. 6A and 13B,C). Calca expression was only detected in two subsets of ChAT⁺ enteric neurons (FIGS. 6B and 13C). These ChAT⁺ enteric neurons also expressed (FIG. 6B): (1) the CGRP receptor genes, (2) the Calcb gene, encoding β-CGRP peptide, which differs in two amino acid from α-CGRP, but has not been substantially studied for its function in immune cells, and (3) the Nmu gene, which Applicants and others have shown amplifies the activity of ILC2s under type 2 inflammation in the lung and small intestine (Cardoso et al., 2017; Klose et al., 2017; Wallrapp et al., 2017).

Applicants confirmed by immunofluorescence staining that ChAT⁺ enteric neurons expressed CGRP (FIG. 6C), and that ILC2s contact with CGRP-expressing neurons at the steady state (FIG. 13D), consistent with previous reports that ILC2s are closely associated with neurons in the intestine (Klose et al., 2017). Thus, CGRP from these ChAT⁺ enteric neurons may regulate ILC2 homeostasis.

Example 7—α-CGRP Suppresses ILC2 Proliferation Through Activating a cAMP Response Module

The presence at homeostasis of α-CGRP receptors on ILC2s and α-CGRP's expression on ChAT⁺ intestinal neurons led Applicants to hypothesize that it has an effect on ILC2s during homeostasis. To test this hypothesis, Applicants next measured the expression profiles of intestinal KLRG1⁺ ILC2s stimulated in vitro by α-CGRP alone, and identified genes differentially expressed under this signal (FIG. 6D, Methods).

Analyzing the profiles suggested that α-CGRP activated a cAMP response module. First, α-CGRP stimulation induced expression of key genes involved in adenylate cyclase-mediated GPCR signaling, including Adrb2, Adora2a, Pde4b and Akap12 (FIG. 6D), as well as cAMP response genes, including Areg (Shao and Sheng, 2010), Crem, and Il5 (FIG. 6D). Indeed, previous studies showed that cAMP directly induces IL5 expression in ILC2s (Nussbaum et al., 2013). Consistently, ATAC-Seq profiling of ILC2s revealed that regions of increased chromatin accessibility following α-CGRP stimulation alone where enriched for gene loci involved in the adenylate cyclase pathway (FIG. 6E and Table 5).

Moreover, α-CGRP stimulation in vitro negatively regulated ILC2 proliferation, and this effect may be mediated by induction of genes involved in cell cycle arrest in the cAMP response module. In the KLRG1⁺ ILC2 cells, α-CGRP induced expression of genes involved in cell cycle arrest, such as Cdkn1a, Gadd45a and Akap12, as well as of key negative regulators of ILC2 expansion, Adrb2 and Pdcd1 (Moriyama et al., 2018; Taylor et al., 2017) (FIG. 6D). cAMP and its principal target, cAMP-dependent protein kinase (PKA), have been previously shown to suppress proliferation via negatively regulating mitogen-activated protein (MAP) kinase cascade in a cell context-dependent manner (Stork and Schmitt, 2002). Indeed, the adenylate cyclase activator forskolin, which increases intracellular cAMP levels (Rodriguez et al., 2013), suppressed the proliferation of ILC2s (FIG. 6F), but not their viability (FIG. 6G). Furthermore, treating ILC2s with an adenylate cyclase inhibitor (Klein et al., 2012) partially rescued the cell proliferation defect mediated by α-CGRP (FIG. 6H). Taken together, the data suggest that α-CGRP suppresses ILC2 proliferation via activating a cAMP response module.

Example 8—At Homeostasis, α-CGRP Maintains ILC2 and Type 2 Responses In Vivo

Finally, Applicants tested if α-CGRP-mediated signaling regulates homeostasis of intestinal KLRG1⁺ ILC2s at steady state in vivo, by analyzing α-CGRP exon knockout (α-CGRP KO) mice, in which the CT exon of Calca gene remains intact (Oh-hashi et al., 2001). The frequency of intestinal KLRG1⁺ILC2s was significantly increased in α-CGRP KO mice compared to wild type (WT) controls (P=0.002, t-test) (FIG. 6I). Type-2 cytokines promote differentiation of tuft cells (Biton et al., 2018; Gerbe et al., 2016; Howitt et al., 2016; von Moltke et al., 2016), and the number of tuft cells was indeed also significantly increased in α-CGRP KO mice (P=0.036, t-test) (FIG. 6J). Thus, α-CGRP-mediated signaling helped maintain the homeostasis of KLRG1⁺ ILC2s and type 2 immunity in the small intestine.

Example 9—Discussion

Here, Applicants collected and analyzed a scRNA-seq atlas of immune cells in the small intestine in homeostasis and during type 2 inflammation, uncovered dynamic responses in cell type specific programs that monitor and titrate mucosal responses, and identified α-CGRP as a key regulator impacting the frequency and activity of intestinal KLRG1⁺ ILC2s.

This work highlights a role for α-CGRP in regulating ILC2s at both homeostasis and during inflammation. Previous studies showed that CGRP signaling can generate both pro- and antiinflammatory immune responses, depending on cell type, tissue and experimental model (Assas et al., 2014). α-CGRP increases IL-5 expression in lung ILC2s co-stimulated with IL-33 (Sui et al., 2018). Mice with deficiency in CRLR in IL-5-expressing cells manifest a normal frequency of ST2⁺ILC2s in lungs exposed to house dust mite (HDM) (Sui et al., 2018), consistent with the finding that ST2⁺ ILC2s in mLNs are not significantly affected by α-CGRP administration. However, this work further reveals that α-CGRP reduced the expansion of intestinal ST2⁻KLRG1⁺ ILC2s in two different inflammatory models. Although differences in cell states between lung ST2⁺ and intestinal ST2⁻KLRG1⁺ ILC2s (Ricardo-Gonzalez et al., 2018) might contribute to their differential reactions to CGRP signaling, additional studies in animal models where CRLR is specifically-deleted in intestinal KLRG1⁺ ILC2s will be needed to elucidate the full molecular mechanism. In addition, it will be important to compare the effects of α-CGRP vs. β-CGRP binding to CRLR in ILC2s.

Applicants show that two subsets of ChAT⁺ enteric neurons are the predominant source of CGRP in the small intestine at steady state. In addition to multiple neuropeptides, these ChAT⁺ neurons also express Il13ra1 and Il4ra (FIG. 13C), which encode the components of the receptor complex for the type 2 cytokine IL-13. Thus, these ChAT⁺ neurons may be specialized for crosstalk with the immune system. Future studies will help determine if cytokine signaling from immune cells during inflammation further boosts the secretion of neuropeptides.

CGRP signaling is an additional key axis of neuro-immune interaction with implications for inflammation, including food allergy. Neuronal signals are emerging as important orchestrators of immune responses in the gastrointestinal tract (Chesne et al., 2018; Godinho-Silva et al., 2018; Veiga-Fernandes and Mucida, 2016). In particular, the nervous system has been shown to exercise dual functions to either activate or inhibit ILC2s via different GPCRs. While NMUR1 signaling amplifies ILC2 activation in the lung and intestines (Cardoso et al., 2017; Klose et al., 2017; Wallrapp et al., 2017), the β2-adrenergic receptor (β²AR) pathway negatively regulates ILC2 expansion (Moriyama et al., 2018).

Applicants thus propose a model for how ILC2s integrate and balance such diverse neural signaling cues, involving different Ga proteins and their downstream signaling (FIG. 7). In this model, the amplifier NMUR1 mainly signals through Gα_q/11and inhibits cAMP levels (Martinez and O'Driscoll, 2015), whereas the negative regulators CRLR and β²AR are both coupled with Gα_sproteins that activate adenylate cyclase and the cAMP pathway (Chatterjee et al., 1993; Madamanchi, 2007). Intracellular cAMP accumulation induces expression of the cAMP response module including IL-5, but suppresses ILC2 proliferation. Thus, selective activation of different subgroups of a subunits of G proteins coupled with variable downstream effects, including the concentration of cAMP, might be utilized by ILC2s to fine-tune the response to neuronal signaling.

Collectively, this work underscores the importance of α-CGRP suppression of ILC2 activity, which may serve as a therapeutic target for treating diseases like food allergy. Since monoclonal antibodies against CGRP have been recently approved to treat migraine (Edvinsson, 2018), it will be important to monitor for the incidence of allergic diseases in treated patients. More broadly, this work provides a resource for understanding the intestinal immune system in response to type 2 inflammation in the context of each specific cell type. Further exploration of the atlas can lead to additional hypotheses on circuits within and between additional cell types that contribute to type 2 immune responses.

Example 10—Experimental Methods

Mice. BALB/cJ mice (Jax 000651) were obtained from the Jackson Laboratory. α-CGRP knock out mice (B6.12956-Calca<tm1Hku>) were kindly provided by Dr. Vijay K. Kuchroo (Brigham and Women's Hospital, Boston, Mass., USA). Mice were housed in specific pathogenfree conditions and were used and maintained in accordance with the Institutional Animal Care and Use Committee (IACUC) protocol #0055-05-15.

To induce allergic reaction to OVA, 6 to 7 weeks old mice were sensitized twice, two weeks apart, with 50 μg of OVA plus 1 mg of aluminum potassium sulfate adjuvant via intraperitoneal injection. Two weeks later, mice were orally administered with 50 mg of OVA on every other day for a total of five times. 1 μg of α-CGRP peptide was administered simultaneously when indicated. Mice were deprived of food for 3-4 hours in cages with wood chip bedding for limiting antigen degradation in the stomach before each intragastric challenge.

To activate ILC2s in vivo, 200 ng of IL-25 was intraperitoneally injected into 7-10 weeks old mice daily for two days. 1 μg α-CGRP was injected together as noted.

Isolation of cells from Peyer's patches (PPs). Peyer's patches (PPs) were carefully dissected from the small intestine under a stereo microscope using a fine scissor, pierced once with a fine forcep. Tissues were digested in freshly made digestion buffer (RPMI-1640 containing 100 μg/ml Liberase™ and 50 μg/ml DNase I at 37° C. on a roto-mixer. After 15 min, tissues were very gently mixed using a 1 ml pipette. The supernatant was collected and added to ice-cold MACS buffer (pH 7.4; PBS plus 2% FCS and 2 mM EDTA). Pre-warmed (37° C.) fresh digestion buffer was added to the remaining tissues. After rotation at 37° C. for 15 min, the mixture was vigorously mixed using a 1 ml pipette for 1 min. Supernatants from the two steps were combined and passed through 70 μm filters and stained for FACS (below).

Isolation of cells from the lamina propria (LP). The small intestines were opened longitudinally and washed in ice-cold PBS. For scRNA-seq, roughly 0.5 cm of fragments from each of the distal, middle and proximal regions without visible PPs were collected. Epithelial cells were dissociated by tissue rotation in pre-warmed (37° C.) PBS containing 10 mM EDTA at 37° C. for 15 min, followed by additional incubation on ice for 15 min. Tissues were then shaken vigorously. After washing twice with PBS containing 2% FCS, tissues were digested in pre-warned (37° C.) digestion buffer at 37° C. on a roto-mixer for 25 min. The supernatants were then passed through 70 μm filters and stained for FACS.

For experiments other than scRNA-seq, the entire small intestine was cut into 1 cm pieces after eliminating PPs. Epithelial cells dissociation was performed by stirring tissues in flasks containing PBS and 10 mM EDTA on a magnetic stirrer at 37° C. two times for 15 min. After vortex, the tissue was stirred in pre-warmed (37° C.) digestion buffer for 25 min at 37° C. The supernatant was passed through 100 μm filter. Leukocytes were further enriched by a 40%/70% Percoll gradient centrifugation before flow staining.

Flow cytometry and cell sorting. Cells were washed and suspended in MACS buffer (pH 7.4; PBS plus 2% FCS and 2 mM EDTA). Nonspecific antibody binding was blocked with CD16/CD32 (2.4G2) antibody for 15 min on ice. Cells were then stained with antibody cocktails for 30 min at 4° C. Lineage-positive cells were excluded for analyzing ILCs by staining for CD3ε (145-2C11), CD5 (53-7.3), CD19 (6D5), CD11b (M1/70), CD8 (53-6.7), CD11c (N418), Gr-1 (RB6-8C5), TCRγδ (eBioGL3 (GL-3, GL3)) and TCRβ (H57-597). To analyze mast cells, lineage-positive cells were excluded by staining for CD3ε, CD5, CD19, CD11c and SiglecF (E50-2440). For surface staining, antibodies for KLRG1 (2F1), CD45 (30-F11), CD127 (A7R34), CCR6 (29-2L17), NKp46 (29A1.4), CD90.2 (53-2.1), FcεRI (Mar-1), IgD (11-26c.2a) and ST2 (DJ8) were used. For intracellular staining, cells were fixed and permeabilized using the Foxp3 transcription factor staining buffer set, followed by staining with anti-GATA-3 (TWAJ) or anti-RORγt (B2D) antibodies. Dead cells were excluded with 7-AAD or Fixable Viability Dye eFluor 780. Flow cytometry was performed on Cytoflex (Beckman Coulter) and analyzed with FlowJo software. Sorting was performed with the SH800S Cell Sorter (Sony Biotechnology).

Droplet-based scRNA-seq. Single cells were captured via the GemCode Single Cell Platform using the GemCode Gel Bead, Chip and Library Kits (10× Genomics), according to the manufacturer's protocol. Briefly, flow-sorted cells were suspended in PBS containing 0.4% BSA, and loaded at 7,000 cells per channel. The cells were then partitioned into GemCode instrument, where individual cells were lysed and mixed with beads carrying unique barcodes in individual oil droplets. The products were subjected to reverse transcription, emulsion breaking, cDNA amplification, shearing, 5′ adaptor and sample index attachment. Libraries were sequenced on a HiSeq 2500 (Illumina).

Quantitative real-time PCR. RNA was isolated from 10,000 cells per sample using PicoPure RNA Isolation Kit, according to the manufacturer's protocol and reverse transcribed to cDNA with iScript cDNA Synthesis Kit. Gene expression was analyzed by quantitative real-time PCR on a ViiA7 System (Thermo Fisher Scientific) using iTaq™ Universal SYBR® Green Supermix with the indicated primers. Expression values were calculated relative to Gapdh detected in the same sample by qPCR.

ILC2 culture. Sort-purified intestinal KLRG1⁺ ILC2s were incubated in RPMI supplemented with 10% FCS, 10 mM Hepes, 1 mM sodium pyruvate, 10% FBS, 80 μm 2-mercaptoethanol, 2 mM glutamine, 100 U/ml penicillin, 100 m/ml streptomycin, 100 ng/ml IL-2 and 100 ng/ml IL-7 in 96-well round bottom plate at 37° C. and 5% CO2. If indicated, the culture was supplemented with 100 ng/ml IL-25. For the in vitro proliferation assay, cells from different mice were pooled and labeled with CellTrace Violet, and then cultured at 1,000-1,500 cells per well with 10 μg/ml α-CGRP for 60 hours. When indicated, 10 μM forskolin or 1 μM SQ 22, 536 in DMSO was supplied and cells were cultured for 40 hours. For bulk RNA-seq, cells from individual mice were stimulated at 200 cells per well with 0.4 μg/ml α-CGRP for 3 hours. For bulk ATAC-seq, cells were stimulated with 0.4 μg/ml α-CGRP for 2 hours.

Immunofluorescence staining and imaging. The small intestines were fixed in 2% PFA, embedded in O.C.T. Compound and sliced into 10 μm by frozen section. The slides were blocked with 0.1% Triton X-100, 2% FCS and donkey serum. The staining reagents incudes Alexa Fluor 594 anti-IgD (11-26.2a), Alexa Fluor 647 anti-CD138 (281-2), eFluor 450 anti EPCAM (G8.8), Alexa Fluor 594 anti-CD3ε (17A2), Alexa Fluor 488 anti-Podoplanin (eBio8.1.1 (8.1.1)), rat anti-CCL21/6 (59106), goat anti-IL-33 (polyclonal), hamster anti-KLRG1 (2F1), rat anti-CGRP (polyclonal), goat anti-ChAT (polyclonal), rabbit anti-DCAMKL1 (polyclonal), Alexa Fluor 647-donkey anti-goat IgG, Alexa Fluor 647 donkey anti-goat IgG, Cy™3 donkey anti-rat IgG, Alexa Fluor 488 goat antisyrian hamster IgG (H+L), Alexa Fluor 647 goat anti-rabbit IgG (H+L) and DAPI. Slides were mounted with the ProlongGold Antifade reagent and examined with a ZEISS LSM 710 upright microscope using ×10, ×20 air or ×60 oil immersion lens. The images were analyzed with ImageJ.

Bulk RNA-seq. 200 ILC2s from each condition were lysed in 10 ul TCL buffer plus 0.5% 2-Mercaptoethanol. Libraries were processed with SMART-Seq2 (Picelli et al., 2013) with at least three replicates per condition, and paired-end sequenced (75 bp×2) with a 75 cycle Nextseq 500 high output V2 kit.

Reads were aligned to the mouse reference genome (NCBI 38, mm10) using Bowtie (Langmead et al., 2009) with default parameters, and expression abundances were estimated using RSEM software (Li and Dewey, 2011). The differential gene expression analysis was performed with edgeR (Robinson et al., 2010) with default parameters.

Bulk ATAC-seq. ATAC-seq experiment was performed using a published protocol (Buenrostro et al., 2013) with minor modifications. Briefly, 2,000 cells in 5 μl PBS, 17.3 μl H²O and 25 μl of transposition buffer (66 mM Tris-acetate, 132 mM K-acetate, 20 mM Mg-acetate, 32% DMF, and 0.2% NP-40) were mixed and incubated at room temperature for 10 min. After adding 2.5 μl of Tn5 transposase to the reaction, the transposition was carried out at 37° C. for 30 min with gentle shaking at 300 rpm and then purified with Zymo DNA Clean and Concentrator (Zymo Research). The library was amplified for 11 cycles, purified with Zymo DNA clean (Zymo Research), and sequenced on an Illumina Next-seq platform using 75 cycle Nextseq 500 high output V2 kit (Read 1: 38 cycles, Index 1: 8 cycles, Index 2: 8 cycles, Read 2: 38 cycles).

The reads were trimmed and aligned to the mouse reference genome (mm9) with Bowtie2 aligner (Langmead and Salzberg, 2012) using the option-X2000. Then, Applicants discarded reads with alignment quality<Q30, improperly paired, mapped to the unmapped contigs, chrY, and mitochondria. Duplicates were removed using Picard tools (function MarkDuplicates, broadinstitute.github.io/picard/). MACSv2 peak caller (Zhang et al., 2008) (version: 2.1.1) was used to call accessible regions of open chromatin regions (ATAC-Seq peaks) with the following parameters (-nomodel -nolambda -keep-dup -call-summits). Peaks overlapping with ENCODE blacklisted regions were filtered out using BEDtools (function itersectBed). Peak summits were extended by ±250 bp, and fragment counts in peaks were calculated using chromVAR (Schep et al., 2017) (version: 1.1.1). Peaks were allocated to genes using GREAT (McLean et al., 2010) (version: 3.0.0) with “basal plus extension” association rule with default parameters. Functional enrichment analysis was performed using GREAT (version: 3.0.0).

Example 11—Computational Methods

scRNA-seq data QC and pre-processing. Reads were aligned to the mouse reference genome (NCBI 38, mm10) using Cell Ranger v2.1.1 (10× Genomics) to generate cell-gene count matrices. After removing cells with less than 500 UMIs and high mitochondrial RNA UMIs (more than four times of the median number of mitochondrial UMIs across cells), Applicants obtained 36,797 cells from PP regions (15,939 cells from OVA-allergic mice and 20,858 cells from controls), and 21,270 cells from LP (11,405 cells from OVA-allergic mice and 9,865 cells from controls). 19,221 genes were retained after filtering genes expressed in less than five cells.

Applicants expected batch effects in the data, because libraries were prepared and sequenced at different times, and because Applicants used two sorting strategies to remove either IgD⁺ Naive B cells or CD19+/CD3⁺ cells. Moreover, the number of recovered cells varied across experiments; for example, Applicants recovered 10,567, 6,439, 5,016, 4,571, and 10,204 cells from each of the five experiments for cells from PPs. Applicants explored several possibilities to address these confounders. Two recent methods have been developed to align scRNA-seq data from different batches (Butler et al., 2018; Haghverdi et al., 2018). However, a cell type must be shared by all datasets for Seurat's CCA approach to correctly align cells (Butler et al., 2018), which is not appropriate for this case. mnnCorrect (Haghverdi et al., 2018) can merge datasets with private (distinct) cell types, but in the datasets where there were dozens of cell types, mnnCorrect successfully merged only some of these clusters, and failed to align cells from other clusters. (More recent methods (Korsunsky et al., 2018; Lin et al., 2018; Stuart et al., 2018; Welch et al., 2018) might help merge cells from different experiments but were published when this analysis was long completed.)

Principal Component Analysis (PCA) is typically used to extract a small number of features (principal components (PCs)) from a normalized gene-cell count matrix. These feature vectors were used for clustering analysis or as inputs for visualization. Unfortunately, in the presence of batch effects, some of the top features typically captured batch effects (Chen et al., 2011). Therefore, batch effects could not be removed by discarding the features with small eigenvalues in PCA.

To help address these batch effects, Applicants took an alternative approach, where Applicants projected the scRNA-seq data to a reference dataset consisting of microarray measurements of immune cells from 276 samples (Heng et al., 2008). Specifically, Applicants first did PCA on the microarray data and extracted the first 101 eigenvectors. Applicants discarded the first eigenvector as the corresponding first PC was correlated with batch information in the microarray data. Applicants next projected the scRNA-seq data to the 100-dimensional space spanned by the eigenvectors (PCs 2-101) from the microarray data. The coordinates of cells in the 100-dimensional space were used for clustering and as inputs of scvis.

scRNA-seq clustering of PP cells. Applicants used the Louvain community detection algorithm (Blondel et al., 2008; Levine et al., 2015) to cluster cells from Peyer's patch regions. As the Louvain clustering algorithm tends to miss some small clusters, Applicants used densityCut (Ding et al., 2016) to find the likely cluster centers. For each center, Applicants changed the edge weights (w′) connecting the cluster center to its neighbors to (w′)=2 kw, where k is the number of nearest neighbors in the k-nearest neighbor (k-NN) graph, and w is the original edge weight of an edge. Louvain clustering on this edge re-weighed graph produced 46 clusters.

Next, Applicants assessed the robustness of the cell to cluster assignment. For each cluster and each batch, Applicants computed the ‘bulk’ gene expression profile of the cells from a given batch in the cluster. The ‘bulk’ gene expression profile for a set of cells is computed by first taking the sum of the gene expression vectors from these cells, where the gene expression vector of a cell was the raw UMI count vector, one element for a gene. The dimensionality of a gene expression vector was the number of genes. To make the bulk gene expression vectors from different sets of cells comparable, a bulk gene expression vector was normalized by dividing the total number of UMIs from all the cells used in computing that bulk gene expression vector, and further multiplying by 10⁴and finally taking the log transform (adding one before the log transformation to make all the elements of the bulk vector positive). Then, for each cell, Applicants computed its Pearson correlation coefficient with the “bulk” profile for each cluster. Applicants denote the maximum correlation between a cell x and the bulk profiles of cluster i (from different batches) as c′. If cell x is originally assigned to cluster j, and c^j<0.9c^k, then Applicants reassign cell x to cluster k. Only ˜0.26% (97 of 36,797) cells were re-assigned to clusters different from their original assignment. Applicants also tested whether two clusters should be merged, if there are no more than 10 significantly differentially expressed genes between them (with differential expression estimated with the Wilcoxon rank-sum test in the package Seurat (Butler et al., 2018)). However, none of the 46 clusters required merging by this criterion.

Clustering cross-validation of PP cells. Applicants performed a 10-fold cross validation analysis on the PP data to evaluate the quality of the clustering. Applicants partitioned the PP data into ten approximately equal size sets, and trained a knearest neighbor (k-NN) classifier (Applicants used a small k=11 as some clusters are small, e.g., 17 cells in cluster 46) on nine folds of data, leaving one fold of data for testing. Applicants repeated this training and testing scheme ten times such that all the data points were used for testing only once.

The k-NN classifiers had a high overall accuracy of 97.2%. Classification accuracy varied for cells from different clusters, with those from cluster 39 having the lowest accuracy of 65.6%. Cluster 39 consisted of a mixture of low-quality plasma B cells and cell doublets (macrophage and epithelial cell doublets). A subgroup of cells expressed plasma B cell marker genes, such as Jchain and Mzb1, but had a relatively small number of UMIs per cell compared to the cells from the plasma cell Cluster 20 (FIG. 8D). Some of these low-quality plasma B cells also had high mitochondrial UMI ratios. Another subset of cells in Cluster 39 expressed both epithelial cell markers (e.g., Epcam and Krt8) and macrophage marker genes (e.g., Lyz1 and Lyz2). These cells had a very large number of UMIs per cell (FIG. 8D) and likely represented potential macrophage and epithelial cell doublets. Notably, although the number of cells in each cluster was extremely unbalanced (e.g., 6,948 cells in cluster 1 but only 17 cells in cluster 46), the classification accuracies were largely uncorrelated with the number of cells in each cluster.

Cluster annotation and filtering of PP cells. Applicants next used MAST (Finak et al., 2015) to identify significantly up-regulated marker genes for each of the 46 clusters, accounting for batch (experimental dates) and the scaled number of detected genes in each cell as covariants (Soneson and Robinson, 2018). Based on known function of the marker genes, Applicants annotated 6 major cell lineages/groups: T cells, B cells, dendritic cells, ILCs, myeloid cells and stromal cells.

Applicants conservatively excluded from further analyses the smallest clusters (<0.05% of all cells) and several ambiguous clusters that Applicants could not confidently assign with cell identities. Applicants note that the small clusters may be biologically valid, but the small number of cells limits the ability to further study them here. For example, the top markers of cluster 45 (18 cells) included Dntt, Rag1, Chrna9, Tctex1d1, Arpp21, which are highly expressed in progenitors of T cells at the double-positive stage in Immgen (Heng et al., 2008; Painter et al., 2011). Cluster 46 (17 cells) may consist of lymph node lymphatic endothelial cells, as they expressed their known marker genes such as Lyve1, Prox1, and Cp. Experimental validations are required for confidently including them in the downstream analyses. Cells in Cluster 34 (100 cells) from PP, expressed both pDC and myeloid gene markers. Only two marker genes (Gtf2a1 and 2310001H17Rik) overlapped between Cluster 34, and either of its adjacent clusters in scvis, clusters 6 and 22 (FIG. 1B). Gtf2a1 was expressed lowly in about 25% of the cluster 34 cells and 2310001H17Rik was expressed in several other cell types, such as T cells and neutrophils. Applicants annotated cluster 34 as ‘Unresolved’. Cluster 18 and cluster 37 were also annotated as ‘Unresolved’ based on similar analysis. Cluster 40 cells expressed macrophages marker gene like Lyz2. Compared to the macrophage cluster (cluster 22), cluster 40 cells expressed higher level of C1qa, C1qb, and C1qc. However, Cluster 40 cells had less UMIs per cells (FIG. 8D) than Cluster 22 cells. Applicants also labeled Cluster 40 as ‘Unresolved’.

Applicants further removed clusters enriched for doublets. To this end, Applicants analyzed PP cells with Scrublet (Wolock et al., 2018), identifying clusters 29, 41, and 43 cells with high doublet scores, together accounting for 0.63% (232 of 36,797) of the PP cells. Cluster 42 cells also had high doublet scores, albeit lower than these other three clusters, and may be further potential doublets.

Clustering LP cells. Applicants used the 35,691 PP cells that were both confidently assigned to clusters in the crossvalidation above and had a k-NN probability greater than 0.5, to train a k-NN classifier (k=11), and used it to classify the 21,270 LP cells. The vast majority of LP cells (97.4%, 20,724/21,270) were assigned to 42 of the 46 clusters with k-NN probability greater than 0.5. Applicants refined the clustering as done for the Peyer's patch data but only for the cells with k-NN probabilities less than 0.5. This reassigned only 0.12% (26/21,270) cells. 34 of the 42 clusters had >15 cells. To find potential LP-specific clusters (cell types that were only observed in LP), Applicants concatenated the data from PPs and LP and then clustered the merged data. Of the clusters enriched in cells from LP (more than three times the number of cells from LP than PPs), two consisted of mast cells and three of plasma B cells. One of these clusters had cells with a low number of UMIs per cell without apparent marker genes. One LP-enriched cluster consisted of fibroblasts that expressed marker genes, such as Col15a1, Ecm1, and Col6a5.

Ten-fold cross validation of the 21,223 LP cells in 34 clusters with >15 cells showed 94.59% accuracy for all cells. Cells from three small clusters 5, 19, and 42 (32, 41, and 19 cells, respectively) had relatively low cross-validation accuracies of 0.41, 0.56, and 0.53, respectively. Overall, ˜93.70% (19,886/21,223) were assigned robustly (correctly classified in crossvalidation and with k-NN probabilities greater than 0.5).

Cellular composition changes. As different gating strategies (IgD^lowor CD3⁻CD19⁻) directly influenced the frequencies of T and B cells, which subsequently affected the proportions of all other cell types, Applicants separately quantified cell compositions in B cells, T cells, and other non-TB cell types. In addition, for analyzing changes in the composition of B cell subsets, Applicants did not include cells from the experiments with CD3⁻CD19⁻ sorting.

Applicants used the negative binomial regression model with treatment (OVA or PBS) and spatial information (PP or LP) as covariates. The total number of analyzed cells (e.g., the total number of T cells when quantifying T cells variations) from each experiment was used as an offset variable. The P value for the significance of treatment (OVA) on a cell type was assessed using the Wald test on the regression coefficient. Applicants performed similar analyses to quantify cell composition changes between PPs and LP but only using cells in homeostasis. In addition, Applicants used spatial information (PP or LP) as a covariate and the total number of analyzed cells from each experiment as an offset variable. The P value for the significance of location information (LP) on a cell type was also assessed using the Wald test on the regression coefficient.

Cell sampling frequencies. To estimate the number of required cells such that Applicants have the power to recover rare cell types, Applicants used the online tool: http://satijalab.org/howmanycells. The method assumes that the probability of observing at least N cells of a cell type in a sample of size K can be modeled by the cumulative distribution function of a negative binomial NBcdf(K; N, p), where p is the relative abundance of this cell type.

Topic modeling. To help guide LDA to find the informative topics, Applicants learned multiple topic models for each subgroup of cells separately. (Applicants had found that topic modeling of all subsets together mostly identifies cell type programs; data not shown.) Specifically, Applicants used the FitGoM( ) function from the CountClust R package (Dey et al., 2017) to fit LDA topic models to the UMI counts (Bielecki et al., 2018) for cells belonging to each major identified cell type from the LP and PP regions. This resulted in 12 models, two for each of the following cell types: T cells (583 LP cells, 12,187 PP cells), DC cells (3,738 LP cells, 3,530 PP cells), B cells (5,648 LP cells, 7,376 cells), ILC cells (5,484 LP cells, 9,396 PP cells), myeloid cells (1,825 LP cells, 579 PP cells), and stromal cells (90 LP cells, 443 PP cells). Genes starting with ‘Rpl’ or ‘Rps’ were removed from the counts matrix prior to fitting the topic models, leaving a total of 19,108 genes included in each count matrix. The number of topics to fit and the tolerance value are required to run FitGoM( ) function. Thus, for each cell type and region, Applicants fit a range of K and then used compGoM( ) to compute the Bayesian Information Criterion (BIC) the estimated likelihood, from which Applicants calculated the Akaike Information Criterion (AIC). The final choice of K value was primarily guided by the BIC curve; Applicants aimed to choose a K at which the BIC was minimal, or decreasing less quickly. Applicants set the tolerance value to 0.1. The top genes to highlight for each topic were selected using the ExtractTopFeatures( ) function.

Statistical analysis. Mice from which Applicants failed to isolate a sufficient number of live cells for downstream analysis were excluded. Prism 7 (GraphPad Software) was used to perform two-tailed t-test and Fisher's exact test as indicated (except for RNA-seq data). P-values from multiple comparisons were adjusted in R.

Code availability. Code will be made available from bitbucket: bitbucket.org/jerry00/mouse_small_intestine_immune_cell_atlas/src/master/

Data availability. The data are deposited in the Gene Expression Omnibus (GEO; GSE124880, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124880, enter token ciczsgwmxhkptsl into the box), and the Single Cell Portal portals.broadinstitute.org/single cell/study/fasi-immune-mouse-small-intestine.

TABLE 1

Differential expression analysis between the cells in each cluster and the remaining cells

in PP regions, related to FIG. 1. In certain embodiments, the genes can be used as markers

for the cell types represented by each cluster. The table disclosed here represents only

the genes with adjusted p values of 0 or less than or equal to 3.23E−267.

percentage of

percentage of
expressing cells

cluster
expressiing cells
in the
LN (average

p value,

gene
ID
in the cluster
remaining cells
fold change)
p value
adjusted

Igfbp4
1
0.632
0.098
1.05
0.0E+00
0.0E+00

Lef1
1
0.804
0.16
0.87
0.0E+00
0.0E+00

Cd3d
1
0.892
0.241
0.69
0.0E+00
0.0E+00

Trac
1
0.803
0.197
0.68
0.0E+00
0.0E+00

Ms4a4b
1
0.884
0.298
0.64
0.0E+00
0.0E+00

Trbc2
1
0.962
0.484
0.63
0.0E+00
0.0E+00

Cd3g
1
0.907
0.259
0.60
0.0E+00
0.0E+00

Cd3e
1
0.846
0.219
0.60
0.0E+00
0.0E+00

Ms4a6b
1
0.745
0.31
0.51
0.0E+00
0.0E+00

Lat
1
0.755
0.27
0.51
0.0E+00
0.0E+00

Dapl1
1
0.327
0.061
0.47
0.0E+00
0.0E+00

Klf2
1
0.91
0.57
0.45
0.0E+00
0.0E+00

Bcl2
1
0.744
0.487
0.43
0.0E+00
0.0E+00

S1pr1
1
0.469
0.113
0.39
0.0E+00
0.0E+00

Atp1b3
1
0.635
0.311
0.39
0.0E+00
0.0E+00

Cd2
1
0.651
0.262
0.37
0.0E+00
0.0E+00

Arl4c
1
0.48
0.153
0.37
0.0E+00
0.0E+00

Skap1
1
0.674
0.307
0.37
0.0E+00
0.0E+00

Bcl11b
1
0.456
0.119
0.35
0.0E+00
0.0E+00

Cd247
1
0.488
0.14
0.34
0.0E+00
0.0E+00

Ccr7
1
0.617
0.233
0.33
0.0E+00
0.0E+00

Fxyd5
1
0.9
0.633
0.33
0.0E+00
0.0E+00

Satb1
1
0.622
0.33
0.33
0.0E+00
0.0E+00

Pdlim4
1
0.295
0.026
0.32
0.0E+00
0.0E+00

Thy1
1
0.546
0.24
0.32
0.0E+00
0.0E+00

Dgka
1
0.439
0.137
0.31
0.0E+00
0.0E+00

Wdr89
1
0.958
0.84
0.31
0.0E+00
0.0E+00

Dusp10
1
0.36
0.167
0.31
0.0E+00
0.0E+00

Actn1
1
0.419
0.109
0.31
0.0E+00
0.0E+00

Cd27
1
0.632
0.308
0.30
0.0E+00
0.0E+00

Ccnd2
1
0.669
0.374
0.28
0.0E+00
0.0E+00

Lck
1
0.762
0.441
0.28
0.0E+00
0.0E+00

Pik3ip1
1
0.416
0.152
0.28
0.0E+00
0.0E+00

Ass1
1
0.394
0.108
0.28
0.0E+00
0.0E+00

Cd28
1
0.464
0.184
0.27
0.0E+00
0.0E+00

Npc2
1
0.878
0.57
0.27
0.0E+00
0.0E+00

Cd79a
2
0.995
0.186
1.37
0.0E+00
0.0E+00

Iglc2
2
0.897
0.165
1.26
0.0E+00
0.0E+00

Fcmr
2
0.817
0.1
1.19
0.0E+00
0.0E+00

Ighd
2
0.738
0.028
1.13
0.0E+00
0.0E+00

Ebf1
2
0.971
0.147
1.09
0.0E+00
0.0E+00

Apoe
2
0.618
0.196
1.05
0.0E+00
0.0E+00

H2-DMb2
2
0.966
0.234
0.97
0.0E+00
0.0E+00

Cd74
2
0.998
0.634
0.92
0.0E+00
0.0E+00

H2-Aa
2
0.994
0.44
0.88
0.0E+00
0.0E+00

Cd79b
2
0.952
0.234
0.87
0.0E+00
0.0E+00

Fcer2a
2
0.613
0.049
0.80
0.0E+00
0.0E+00

Ighm
2
0.923
0.379
0.77
0.0E+00
0.0E+00

H2-Eb1
2
0.989
0.397
0.72
0.0E+00
0.0E+00

Iglc3
2
0.886
0.213
0.72
0.0E+00
0.0E+00

Bank1
2
0.628
0.057
0.69
0.0E+00
0.0E+00

H2-Ab1
2
0.99
0.476
0.69
0.0E+00
0.0E+00

Cd72
2
0.628
0.17
0.63
0.0E+00
0.0E+00

Hvcn1
2
0.712
0.237
0.60
0.0E+00
0.0E+00

Cd83
2
0.735
0.25
0.58
0.0E+00
0.0E+00

Vpreb3
2
0.635
0.111
0.58
0.0E+00
0.0E+00

Tnfrsf13c
2
0.687
0.125
0.57
0.0E+00
0.0E+00

Cd37
2
0.902
0.551
0.56
0.0E+00
0.0E+00

Ms4a1
2
0.876
0.142
0.56
0.0E+00
0.0E+00

Mef2c
2
0.811
0.249
0.56
0.0E+00
0.0E+00

Snn
2
0.524
0.058
0.55
0.0E+00
0.0E+00

Cd52
2
0.991
0.862
0.54
0.0E+00
0.0E+00

Fcrl1
2
0.493
0.077
0.51
0.0E+00
0.0E+00

Capg
2
0.635
0.284
0.45
0.0E+00
0.0E+00

Ly6d
2
0.301
0.031
0.44
0.0E+00
0.0E+00

Ifi30
2
0.787
0.264
0.44
0.0E+00
0.0E+00

Scd1
2
0.404
0.039
0.43
0.0E+00
0.0E+00

Siglecg
2
0.569
0.151
0.42
0.0E+00
0.0E+00

H2-Ob
2
0.542
0.131
0.41
0.0E+00
0.0E+00

H2-Oa
2
0.545
0.185
0.40
0.0E+00
0.0E+00

Fcrla
2
0.535
0.137
0.40
0.0E+00
0.0E+00

Ly6e
2
0.673
0.332
0.39
0.0E+00
0.0E+00

Pou2f2
2
0.578
0.204
0.39
0.0E+00
0.0E+00

Cd19
2
0.496
0.098
0.38
0.0E+00
0.0E+00

Sapcd1
2
0.286
0.035
0.38
0.0E+00
0.0E+00

A530040E14Rik
2
0.395
0.099
0.38
0.0E+00
0.0E+00

Napsa
2
0.686
0.238
0.37
0.0E+00
0.0E+00

H2-DMa
2
0.768
0.3
0.36
0.0E+00
0.0E+00

AC125149.3
2
0.36
0.094
0.36
0.0E+00
0.0E+00

Fam43a
2
0.34
0.058
0.35
0.0E+00
0.0E+00

Cd55
2
0.347
0.05
0.35
0.0E+00
0.0E+00

Dok3
2
0.44
0.096
0.33
0.0E+00
0.0E+00

Pold4
2
0.683
0.338
0.31
0.0E+00
0.0E+00

Blk
2
0.362
0.08
0.31
0.0E+00
0.0E+00

Cxcr4
2
0.562
0.31
0.30
0.0E+00
0.0E+00

Lmo2
2
0.386
0.105
0.29
0.0E+00
0.0E+00

Chchd10
2
0.549
0.213
0.28
0.0E+00
0.0E+00

Ralgps2
2
0.393
0.133
0.28
0.0E+00
0.0E+00

Cxcr5
2
0.329
0.097
0.27
0.0E+00
0.0E+00

Pkig
2
0.611
0.225
0.27
0.0E+00
0.0E+00

Serpinb1a
2
0.481
0.182
0.26
0.0E+00
0.0E+00

Ms4a4c
2
0.28
0.066
0.26
0.0E+00
0.0E+00

Cd22
2
0.35
0.078
0.26
0.0E+00
0.0E+00

Unc93b1
2
0.593
0.246
0.25
0.0E+00
0.0E+00

Ptpn6
2
0.714
0.426
0.25
0.0E+00
0.0E+00

Ptp4a3
2
0.62
0.336
0.25
0.0E+00
0.0E+00

Dusp2
2
0.616
0.354
0.34
4.4E−299
8.4E−295

Foxp1
2
0.646
0.435
0.28
2.2E−292
4.3E−288

Cxcr6
3
0.935
0.166
1.27
0.0E+00
0.0E+00

Car2
3
0.915
0.198
1.21
0.0E+00
0.0E+00

Lgals3
3
0.938
0.232
1.17
0.0E+00
0.0E+00

Tmem176b
3
0.975
0.222
1.17
0.0E+00
0.0E+00

Tmem176a
3
0.952
0.203
1.07
0.0E+00
0.0E+00

Serpinb1a
3
0.777
0.161
1.03
0.0E+00
0.0E+00

AW112010
3
0.991
0.553
0.96
0.0E+00
0.0E+00

Upp1
3
0.722
0.068
0.93
0.0E+00
0.0E+00

Il7r
3
0.911
0.348
0.89
0.0E+00
0.0E+00

Sepp1
3
0.904
0.35
0.88
0.0E+00
0.0E+00

Junb
3
0.964
0.736
0.88
0.0E+00
0.0E+00

Ffar2
3
0.693
0.091
0.84
0.0E+00
0.0E+00

Itm2b
3
0.999
0.83
0.83
0.0E+00
0.0E+00

Id2
3
0.824
0.32
0.83
0.0E+00
0.0E+00

Lmo4
3
0.86
0.286
0.83
0.0E+00
0.0E+00

Klrk1
3
0.742
0.154
0.82
0.0E+00
0.0E+00

Emb
3
0.914
0.413
0.81
0.0E+00
0.0E+00

Gadd45b
3
0.621
0.27
0.81
0.0E+00
0.0E+00

Tcrg-C1
3
0.637
0.078
0.80
0.0E+00
0.0E+00

Rora
3
0.756
0.153
0.76
0.0E+00
0.0E+00

Ncoa7
3
0.687
0.155
0.75
0.0E+00
0.0E+00

Rgs1
3
0.737
0.339
0.75
0.0E+00
0.0E+00

Zfp36l1
3
0.945
0.582
0.74
0.0E+00
0.0E+00

Ncr1
3
0.709
0.116
0.69
0.0E+00
0.0E+00

Ifngr1
3
0.814
0.41
0.67
0.0E+00
0.0E+00

Ckb
3
0.802
0.189
0.67
0.0E+00
0.0E+00

Btg2
3
0.924
0.708
0.66
0.0E+00
0.0E+00

Serpina3g
3
0.578
0.134
0.66
0.0E+00
0.0E+00

Ikzf2
3
0.705
0.182
0.66
0.0E+00
0.0E+00

Gimap3
3
0.88
0.487
0.65
0.0E+00
0.0E+00

Nfkbia
3
0.856
0.554
0.62
0.0E+00
0.0E+00

Hcst
3
0.872
0.502
0.62
0.0E+00
0.0E+00

Pim1
3
0.823
0.476
0.61
0.0E+00
0.0E+00

Ctsw
3
0.705
0.212
0.58
0.0E+00
0.0E+00

Fcer1g
3
0.904
0.324
0.58
0.0E+00
0.0E+00

Cd69
3
0.726
0.391
0.56
0.0E+00
0.0E+00

Stk19
3
0.567
0.125
0.56
0.0E+00
0.0E+00

Bhlhe40
3
0.688
0.266
0.56
0.0E+00
0.0E+00

St6galnac3
3
0.633
0.134
0.56
0.0E+00
0.0E+00

S100a10
3
0.914
0.561
0.55
0.0E+00
0.0E+00

Il18r1
3
0.592
0.116
0.55
0.0E+00
0.0E+00

Podnl1
3
0.625
0.132
0.54
0.0E+00
0.0E+00

Ltb
3
0.958
0.812
0.53
0.0E+00
0.0E+00

Chad
3
0.55
0.086
0.52
0.0E+00
0.0E+00

Cd82
3
0.817
0.405
0.51
0.0E+00
0.0E+00

Gimap4
3
0.821
0.441
0.51
0.0E+00
0.0E+00

Prr29
3
0.51
0.078
0.50
0.0E+00
0.0E+00

Txk
3
0.747
0.338
0.50
0.0E+00
0.0E+00

Sla
3
0.629
0.265
0.49
0.0E+00
0.0E+00

Asb2
3
0.507
0.118
0.49
0.0E+00
0.0E+00

Serpinb6b
3
0.461
0.138
0.48
0.0E+00
0.0E+00

Maf
3
0.527
0.115
0.48
0.0E+00
0.0E+00

Ramp3
3
0.345
0.086
0.47
0.0E+00
0.0E+00

Serpinb9
3
0.41
0.115
0.47
0.0E+00
0.0E+00

Maff
3
0.508
0.156
0.45
0.0E+00
0.0E+00

Ahcyl2
3
0.584
0.204
0.45
0.0E+00
0.0E+00

Hk2
3
0.361
0.053
0.45
0.0E+00
0.0E+00

Nrip1
3
0.652
0.303
0.44
0.0E+00
0.0E+00

Icos
3
0.468
0.118
0.44
0.0E+00
0.0E+00

Tnfrsf25
3
0.527
0.12
0.44
0.0E+00
0.0E+00

2010300C02Rik
3
0.455
0.073
0.43
0.0E+00
0.0E+00

Cd160
3
0.503
0.103
0.42
0.0E+00
0.0E+00

Rorc
3
0.437
0.064
0.41
0.0E+00
0.0E+00

Nrgn
3
0.509
0.141
0.40
0.0E+00
0.0E+00

Selplg
3
0.901
0.574
0.40
0.0E+00
0.0E+00

Tcrg-C4
3
0.366
0.079
0.38
0.0E+00
0.0E+00

C4b
3
0.288
0.026
0.38
0.0E+00
0.0E+00

Ahr
3
0.463
0.151
0.38
0.0E+00
0.0E+00

Cxcr3
3
0.413
0.078
0.38
0.0E+00
0.0E+00

Kcnk1
3
0.397
0.048
0.37
0.0E+00
0.0E+00

Slc6a20a
3
0.28
0.01
0.37
0.0E+00
0.0E+00

Tspo
3
0.864
0.578
0.36
0.0E+00
0.0E+00

F2r
3
0.385
0.076
0.36
0.0E+00
0.0E+00

Fgl2
3
0.385
0.1
0.35
0.0E+00
0.0E+00

Prelid2
3
0.444
0.124
0.34
0.0E+00
0.0E+00

Kit
3
0.436
0.109
0.33
0.0E+00
0.0E+00

Klrb1b
3
0.313
0.04
0.32
0.0E+00
0.0E+00

Aqp3
3
0.345
0.045
0.32
0.0E+00
0.0E+00

Dkkl1
3
0.36
0.071
0.31
0.0E+00
0.0E+00

Lpar6
3
0.4
0.108
0.31
0.0E+00
0.0E+00

St3gal6
3
0.441
0.141
0.31
0.0E+00
0.0E+00

Cd7
3
0.733
0.349
0.31
0.0E+00
0.0E+00

Mdfic
3
0.388
0.108
0.31
0.0E+00
0.0E+00

Ppt2
3
0.359
0.081
0.31
0.0E+00
0.0E+00

Klrb1f
3
0.373
0.084
0.30
0.0E+00
0.0E+00

Il2ra
3
0.357
0.084
0.30
0.0E+00
0.0E+00

Tmem64
3
0.396
0.12
0.30
0.0E+00
0.0E+00

Prrt1
3
0.337
0.051
0.30
0.0E+00
0.0E+00

Cited4
3
0.408
0.11
0.30
0.0E+00
0.0E+00

Eef2k
3
0.371
0.082
0.30
0.0E+00
0.0E+00

Actn2
3
0.25
0.028
0.29
0.0E+00
0.0E+00

Lysmd2
3
0.361
0.09
0.29
0.0E+00
0.0E+00

Clnk
3
0.311
0.052
0.27
0.0E+00
0.0E+00

Rbpms2
3
0.267
0.016
0.27
0.0E+00
0.0E+00

Gstm5
3
0.25
0.025
0.27
0.0E+00
0.0E+00

Xlr4a
3
0.338
0.078
0.27
0.0E+00
0.0E+00

Plekhg1
3
0.285
0.037
0.26
0.0E+00
0.0E+00

Tasp1
3
0.326
0.079
0.26
0.0E+00
0.0E+00

Gjb2
3
0.237
0.023
0.26
0.0E+00
0.0E+00

Trbc1
3
0.862
0.426
0.26
0.0E+00
0.0E+00

Bcl2a1d
3
0.45
0.153
0.26
0.0E+00
0.0E+00

Rnase4
3
0.303
0.056
0.25
0.0E+00
0.0E+00

Fhl2
3
0.291
0.055
0.25
0.0E+00
0.0E+00

Acot7
3
0.471
0.177
0.29
3.4E−313
0.0E+00

Il2rb
3
0.514
0.195
0.30
1.1E−311
2.3E−307

Gabarapl1
3
0.318
0.082
0.25
5.9E−311
1.1E−306

Shisa5
3
0.991
0.869
0.35
0.0E+00
4.1E−305

Tnf
3
0.272
0.052
0.31
0.0E+00
3.0E−304

Il22
3
0.264
0.049
1.13
3.3E−302
6.4E−298

Nabp1
3
0.569
0.255
0.46
3.5E−298
6.7E−294

Gem
3
0.587
0.274
0.59
2.1E−297
4.1E−293

Socs2
3
0.301
0.068
0.29
1.1E−293
2.1E−289

Gpr183
3
0.635
0.313
0.36
5.8E−288
1.1E−283

Uhrf2
3
0.564
0.271
0.44
1.3E−286
2.5E−282

Ccdc184
3
0.27
0.054
0.35
9.5E−286
1.8E−281

Wls
3
0.329
0.086
0.25
3.4E−283
6.6E−279

Cers4
3
0.419
0.149
0.30
2.4E−282
4.6E−278

Mast4
3
0.396
0.131
0.29
2.5E−282
4.8E−278

Stk24
3
0.593
0.325
0.31
1.9E−281
3.7E−277

Hbegf
3
0.196
0.027
0.26
5.8E−279
1.1E−274

Dusp5
3
0.616
0.313
0.39
4.6E−275
8.8E−271

Nr4a1
3
0.684
0.362
0.41
2.1E−273
4.0E−269

Il22
4
0.358
0.044
1.64
0.0E+00
0.0E+00

Tmem176a
4
0.979
0.209
1.42
0.0E+00
0.0E+00

Odc1
4
0.803
0.24
1.38
0.0E+00
0.0E+00

S100a4
4
0.884
0.11
1.37
0.0E+00
0.0E+00

Fos
4
0.874
0.472
1.33
0.0E+00
0.0E+00

Tmem176b
4
0.976
0.229
1.26
0.0E+00
0.0E+00

Gem
4
0.777
0.262
1.20
0.0E+00
0.0E+00

Junb
4
0.97
0.738
1.15
0.0E+00
0.0E+00

Ckb
4
0.891
0.188
1.05
0.0E+00
0.0E+00

Prr29
4
0.784
0.061
1.05
0.0E+00
0.0E+00

Rasl11a
4
0.603
0.042
1.02
0.0E+00
0.0E+00

Ncoa7
4
0.798
0.151
1.01
0.0E+00
0.0E+00

Itm2b
4
0.999
0.832
1.01
0.0E+00
0.0E+00

Il7r
4
0.951
0.351
1.01
0.0E+00
0.0E+00

Fosb
4
0.623
0.152
0.99
0.0E+00
0.0E+00

Jun
4
0.795
0.38
0.95
0.0E+00
0.0E+00

Sepp1
4
0.944
0.352
0.94
0.0E+00
0.0E+00

Fcer1g
4
0.98
0.324
0.91
0.0E+00
0.0E+00

Cd82
4
0.901
0.403
0.90
0.0E+00
0.0E+00

Ltb
4
0.982
0.812
0.89
0.0E+00
0.0E+00

Id2
4
0.854
0.323
0.89
0.0E+00
0.0E+00

Cd7
4
0.876
0.342
0.88
0.0E+00
0.0E+00

Chad
4
0.724
0.078
0.87
0.0E+00
0.0E+00

Uhrf2
4
0.715
0.262
0.87
0.0E+00
0.0E+00

Cxcr6
4
0.861
0.179
0.87
0.0E+00
0.0E+00

Sdc4
4
0.748
0.168
0.86
0.0E+00
0.0E+00

Cited4
4
0.614
0.097
0.81
0.0E+00
0.0E+00

Hebp1
4
0.565
0.061
0.79
0.0E+00
0.0E+00

Rora
4
0.73
0.162
0.75
0.0E+00
0.0E+00

Nrgn
4
0.719
0.128
0.74
0.0E+00
0.0E+00

Nr4a1
4
0.774
0.359
0.74
0.0E+00
0.0E+00

Ier2
4
0.789
0.512
0.73
0.0E+00
0.0E+00

Dusp1
4
0.749
0.444
0.72
0.0E+00
0.0E+00

Sla
4
0.697
0.263
0.71
0.0E+00
0.0E+00

Fam110a
4
0.55
0.084
0.70
0.0E+00
0.0E+00

Maff
4
0.631
0.15
0.69
0.0E+00
0.0E+00

Gadd45b
4
0.623
0.273
0.68
0.0E+00
0.0E+00

Nfkbia
4
0.914
0.552
0.68
0.0E+00
0.0E+00

Car2
4
0.803
0.215
0.67
0.0E+00
0.0E+00

Zfp36l1
4
0.935
0.587
0.67
0.0E+00
0.0E+00

Dhrs3
4
0.674
0.135
0.67
0.0E+00
0.0E+00

Espn
4
0.591
0.063
0.65
0.0E+00
0.0E+00

Jund
4
0.94
0.813
0.65
0.0E+00
0.0E+00

Ramp1
4
0.719
0.294
0.65
0.0E+00
0.0E+00

Ccr6
4
0.618
0.077
0.64
0.0E+00
0.0E+00

Cd69
4
0.761
0.391
0.63
0.0E+00
0.0E+00

Tnfsf11
4
0.359
0.046
0.63
0.0E+00
0.0E+00

Oser1
4
0.707
0.349
0.63
0.0E+00
0.0E+00

Bhlhe40
4
0.709
0.269
0.62
0.0E+00
0.0E+00

Ccdc184
4
0.47
0.041
0.62
0.0E+00
0.0E+00

Lmna
4
0.393
0.072
0.62
0.0E+00
0.0E+00

Rgs2
4
0.811
0.482
0.61
0.0E+00
0.0E+00

Lmo4
4
0.817
0.295
0.60
0.0E+00
0.0E+00

Rorc
4
0.557
0.059
0.60
0.0E+00
0.0E+00

Egr1
4
0.526
0.186
0.59
0.0E+00
0.0E+00

Cited2
4
0.57
0.23
0.59
0.0E+00
0.0E+00

Lgals3
4
0.742
0.255
0.58
0.0E+00
0.0E+00

Klf4
4
0.457
0.123
0.58
0.0E+00
0.0E+00

Nrip1
4
0.715
0.302
0.57
0.0E+00
0.0E+00

Ffar2
4
0.563
0.107
0.56
0.0E+00
0.0E+00

Emb
4
0.846
0.424
0.56
0.0E+00
0.0E+00

Sfr1
4
0.779
0.346
0.56
0.0E+00
0.0E+00

Cd81
4
0.65
0.232
0.56
0.0E+00
0.0E+00

Tmem59
4
0.848
0.483
0.55
0.0E+00
0.0E+00

Serpina3g
4
0.543
0.142
0.55
0.0E+00
0.0E+00

Tnfrsf25
4
0.607
0.118
0.54
0.0E+00
0.0E+00

Podnl1
4
0.606
0.139
0.53
0.0E+00
0.0E+00

Ube2e3
4
0.589
0.179
0.53
0.0E+00
0.0E+00

Ldhb
4
0.466
0.092
0.53
0.0E+00
0.0E+00

Gpr132
4
0.66
0.261
0.52
0.0E+00
0.0E+00

Upp1
4
0.507
0.091
0.52
0.0E+00
0.0E+00

Kit
4
0.551
0.103
0.51
0.0E+00
0.0E+00

Dgat1
4
0.504
0.116
0.51
0.0E+00
0.0E+00

Arrdc4
4
0.499
0.094
0.50
0.0E+00
0.0E+00

Znrf1
4
0.632
0.219
0.49
0.0E+00
0.0E+00

Slc6a13
4
0.41
0.032
0.49
0.0E+00
0.0E+00

Rabac1
4
0.889
0.614
0.48
0.0E+00
0.0E+00

M1ap
4
0.417
0.037
0.48
0.0E+00
0.0E+00

Il18r1
4
0.548
0.125
0.47
0.0E+00
0.0E+00

Arg1
4
0.265
0.038
0.47
0.0E+00
0.0E+00

Acot7
4
0.573
0.172
0.46
0.0E+00
0.0E+00

Tspo
4
0.871
0.58
0.46
0.0E+00
0.0E+00

Asb2
4
0.504
0.122
0.46
0.0E+00
0.0E+00

Lamp1
4
0.806
0.463
0.46
0.0E+00
0.0E+00

Ostf1
4
0.844
0.573
0.44
0.0E+00
0.0E+00

2010300C02Rik
4
0.456
0.077
0.44
0.0E+00
0.0E+00

Fdx1
4
0.479
0.138
0.44
0.0E+00
0.0E+00

Mast4
4
0.493
0.126
0.44
0.0E+00
0.0E+00

Serpinb1a
4
0.606
0.181
0.43
0.0E+00
0.0E+00

Kcnk1
4
0.435
0.049
0.42
0.0E+00
0.0E+00

Shisa5
4
0.994
0.87
0.42
0.0E+00
0.0E+00

Pxdc1
4
0.379
0.089
0.41
0.0E+00
0.0E+00

Anxa5
4
0.609
0.22
0.41
0.0E+00
0.0E+00

Sec11c
4
0.862
0.516
0.41
0.0E+00
0.0E+00

Tm9sf2
4
0.484
0.149
0.40
0.0E+00
0.0E+00

Itm2c
4
0.733
0.362
0.40
0.0E+00
0.0E+00

St6galnac3
4
0.529
0.147
0.40
0.0E+00
0.0E+00

Cmc2
4
0.562
0.194
0.39
0.0E+00
0.0E+00

Dkkl1
4
0.408
0.07
0.38
0.0E+00
0.0E+00

Nrp1
4
0.354
0.042
0.37
0.0E+00
0.0E+00

Ptges
4
0.319
0.009
0.36
0.0E+00
0.0E+00

Xlr4a
4
0.399
0.076
0.36
0.0E+00
0.0E+00

Il17re
4
0.36
0.028
0.36
0.0E+00
0.0E+00

Il2ra
4
0.39
0.085
0.35
0.0E+00
0.0E+00

S100a6
4
0.553
0.176
0.35
0.0E+00
0.0E+00

Stom
4
0.358
0.034
0.35
0.0E+00
0.0E+00

Piwil4
4
0.291
0.005
0.35
0.0E+00
0.0E+00

Scn1b
4
0.347
0.039
0.35
0.0E+00
0.0E+00

Nmrk1
4
0.339
0.086
0.35
0.0E+00
0.0E+00

Igfbp7
4
0.515
0.05
0.34
0.0E+00
0.0E+00

Slc41a3
4
0.33
0.031
0.34
0.0E+00
0.0E+00

Xlr4c
4
0.415
0.11
0.34
0.0E+00
0.0E+00

Eef2k
4
0.393
0.084
0.33
0.0E+00
0.0E+00

Cntn1
4
0.312
0.014
0.33
0.0E+00
0.0E+00

Xist
4
0.999
0.871
0.33
0.0E+00
0.0E+00

Casp4
4
0.334
0.069
0.32
0.0E+00
0.0E+00

Dtx4
4
0.356
0.064
0.32
0.0E+00
0.0E+00

Hmgn3
4
0.48
0.16
0.31
0.0E+00
0.0E+00

Cx3cl1
4
0.267
0.012
0.31
0.0E+00
0.0E+00

Oaz1
4
0.999
0.945
0.30
0.0E+00
0.0E+00

Dkk3
4
0.309
0.033
0.30
0.0E+00
0.0E+00

Serinc2
4
0.309
0.025
0.29
0.0E+00
0.0E+00

Ret
4
0.298
0.032
0.29
0.0E+00
0.0E+00

Sdc1
4
0.302
0.048
0.29
0.0E+00
0.0E+00

Igf1r
4
0.31
0.053
0.27
0.0E+00
0.0E+00

Clnk
4
0.318
0.054
0.27
0.0E+00
0.0E+00

Ddc
4
0.222
0.022
0.27
0.0E+00
0.0E+00

Cdc14a
4
0.249
0.036
0.27
0.0E+00
0.0E+00

Ptger2
4
0.252
0.03
0.26
0.0E+00
0.0E+00

Vipr2
4
0.261
0.014
0.26
0.0E+00
0.0E+00

Il1r1
4
0.259
0.022
0.25
0.0E+00
0.0E+00

Bcl2
4
0.85
0.511
0.41
2.2E−302
4.2E−298

S100a1
4
0.291
0.058
0.26
2.8E−300
5.3E−296

Aqp3
4
0.29
0.052
0.26
1.1E−299
2.2E−295

Ecm1
4
0.272
0.047
0.29
5.6E−298
1.1E−293

Mrfap1
4
0.789
0.534
0.36
2.9E−297
5.5E−293

Dbp
4
0.306
0.076
0.31
1.4E−289
2.8E−285

Rabgap1l
4
0.607
0.294
0.36
3.5E−287
6.7E−283

Gpx4
4
0.903
0.657
0.38
8.7E−286
1.7E−281

Agtrap
4
0.362
0.1
0.27
2.2E−282
4.2E−278

Tgif1
4
0.558
0.247
0.41
1.3E−280
2.6E−276

Fhl2
4
0.289
0.058
0.27
2.9E−279
5.6E−275

Nfatc2
4
0.31
0.076
0.26
9.3E−278
1.8E−273

Lta
4
0.264
0.06
0.39
3.4E−276
6.6E−272

Sptssa
4
0.786
0.468
0.38
1.2E−274
2.4E−270

Ptms
4
0.618
0.285
0.30
6.8E−274
1.3E−269

Cd8b1
5
0.947
0.092
1.29
0.0E+00
0.0E+00

Cd8a
5
0.799
0.06
0.90
0.0E+00
0.0E+00

Dapl1
5
0.55
0.082
0.86
0.0E+00
0.0E+00

Ms4a4b
5
0.935
0.373
0.76
0.0E+00
0.0E+00

Cd3d
5
0.934
0.326
0.75
0.0E+00
0.0E+00

Cd3e
5
0.912
0.299
0.69
0.0E+00
0.0E+00

Thy1
5
0.793
0.265
0.67
0.0E+00
0.0E+00

Lef1
5
0.818
0.246
0.67
0.0E+00
0.0E+00

Cd3g
5
0.942
0.344
0.62
0.0E+00
0.0E+00

Trbc2
5
0.958
0.549
0.56
0.0E+00
0.0E+00

Trac
5
0.796
0.279
0.54
0.0E+00
0.0E+00

Wdr89
5
0.98
0.854
0.52
0.0E+00
0.0E+00

Lat
5
0.797
0.332
0.51
0.0E+00
0.0E+00

Arl4c
5
0.626
0.188
0.50
0.0E+00
0.0E+00

Nkg7
5
0.818
0.215
0.50
0.0E+00
0.0E+00

Ms4a6b
5
0.799
0.365
0.50
0.0E+00
0.0E+00

Klk8
5
0.572
0.162
0.47
0.0E+00
0.0E+00

Tmsb10
5
1
0.977
0.41
0.0E+00
0.0E+00

Acp5
5
0.595
0.246
0.38
0.0E+00
0.0E+00

Npc2
5
0.909
0.61
0.31
0.0E+00
0.0E+00

Saraf
5
0.76
0.431
0.39
5.5E−314
0.0E+00

Igfbp4
5
0.555
0.175
0.43
1.1E−313
0.0E+00

Ccr7
5
0.678
0.28
0.38
9.7E−298
1.9E−293

Klf2
5
0.931
0.614
0.40
1.4E−276
2.6E−272

Bst2
6
0.998
0.243
2.99
0.0E+00
0.0E+00

Ly6c2
6
0.997
0.082
2.81
0.0E+00
0.0E+00

Tyrobp
6
0.999
0.263
2.67
0.0E+00
0.0E+00

Siglech
6
0.998
0.053
2.67
0.0E+00
0.0E+00

Ccl4
6
0.868
0.134
2.60
0.0E+00
0.0E+00

Klk1
6
0.96
0.041
2.60
0.0E+00
0.0E+00

Plac8
6
0.999
0.204
2.59
0.0E+00
0.0E+00

Cox6a2
6
0.969
0.019
2.42
0.0E+00
0.0E+00

Ly6c1
6
0.991
0.062
2.36
0.0E+00
0.0E+00

Irf8
6
0.997
0.371
2.27
0.0E+00
0.0E+00

Ctsb
6
0.994
0.335
2.20
0.0E+00
0.0E+00

Psap
6
0.998
0.502
2.19
0.0E+00
0.0E+00

Rnase6
6
0.992
0.124
2.15
0.0E+00
0.0E+00

Grn
6
0.986
0.119
2.11
0.0E+00
0.0E+00

Ctsl
6
0.96
0.079
2.01
0.0E+00
0.0E+00

Mpeg1
6
0.983
0.048
1.97
0.0E+00
0.0E+00

D13Ertd608e
6
0.924
0.007
1.92
0.0E+00
0.0E+00

Klk1b27
6
0.965
0.018
1.88
0.0E+00
0.0E+00

Fth1
6
1
0.978
1.80
0.0E+00
0.0E+00

Pld4
6
0.975
0.098
1.78
0.0E+00
0.0E+00

Ctsh
6
0.988
0.27
1.76
0.0E+00
0.0E+00

Ccr9
6
0.956
0.11
1.75
0.0E+00
0.0E+00

Cybb
6
0.978
0.146
1.70
0.0E+00
0.0E+00

Lgals1
6
0.978
0.292
1.68
0.0E+00
0.0E+00

Iglc3
6
0.968
0.236
1.67
0.0E+00
0.0E+00

Tcf4
6
0.977
0.184
1.67
0.0E+00
0.0E+00

Dnajc7
6
0.982
0.321
1.64
0.0E+00
0.0E+00

Clec12a
6
0.93
0.053
1.57
0.0E+00
0.0E+00

Lair1
6
0.937
0.034
1.54
0.0E+00
0.0E+00

Tsc22d1
6
0.908
0.088
1.50
0.0E+00
0.0E+00

Sell
6
0.973
0.28
1.49
0.0E+00
0.0E+00

Cd8b1
6
0.593
0.116
1.48
0.0E+00
0.0E+00

Slpi
6
0.789
0.06
1.47
0.0E+00
0.0E+00

Pgls
6
0.979
0.41
1.45
0.0E+00
0.0E+00

Tspan13
6
0.982
0.462
1.42
0.0E+00
0.0E+00

St8sia4
6
0.927
0.14
1.39
0.0E+00
0.0E+00

Snx5
6
0.974
0.39
1.39
0.0E+00
0.0E+00

Alox5ap
6
0.937
0.052
1.39
0.0E+00
0.0E+00

Ifi27l2a
6
0.844
0.368
1.37
0.0E+00
0.0E+00

P2ry14
6
0.874
0.029
1.35
0.0E+00
0.0E+00

Ly6e
6
0.891
0.331
1.32
0.0E+00
0.0E+00

Atp1b1
6
0.897
0.137
1.31
0.0E+00
0.0E+00

Bcl11a
6
0.889
0.103
1.30
0.0E+00
0.0E+00

Smim5
6
0.781
0.013
1.30
0.0E+00
0.0E+00

Gpx1
6
0.994
0.56
1.29
0.0E+00
0.0E+00

Serp1
6
0.989
0.518
1.29
0.0E+00
0.0E+00

Cd209d
6
0.564
0.009
1.28
0.0E+00
0.0E+00

Rilpl2
6
0.857
0.182
1.28
0.0E+00
0.0E+00

Tagln2
6
0.982
0.598
1.27
0.0E+00
0.0E+00

Upb1
6
0.86
0.017
1.27
0.0E+00
0.0E+00

Pltp
6
0.842
0.042
1.26
0.0E+00
0.0E+00

Ctss
6
0.96
0.357
1.26
0.0E+00
0.0E+00

Ncf1
6
0.861
0.131
1.25
0.0E+00
0.0E+00

Cd47
6
0.981
0.56
1.24
0.0E+00
0.0E+00

Gpr171
6
0.847
0.242
1.23
0.0E+00
0.0E+00

Ctsz
6
0.954
0.316
1.23
0.0E+00
0.0E+00

Cd209a
6
0.578
0.013
1.22
0.0E+00
0.0E+00

Nucb2
6
0.868
0.035
1.22
0.0E+00
0.0E+00

Unc93b1
6
0.934
0.238
1.20
0.0E+00
0.0E+00

Xbp1
6
0.906
0.229
1.20
0.0E+00
0.0E+00

Dap
6
0.95
0.304
1.18
0.0E+00
0.0E+00

Ppfia4
6
0.864
0.034
1.18
0.0E+00
0.0E+00

Rnaset2a
6
0.974
0.54
1.17
0.0E+00
0.0E+00

Tmed3
6
0.896
0.159
1.16
0.0E+00
0.0E+00

Syngr2
6
0.933
0.328
1.15
0.0E+00
0.0E+00

Cadm1
6
0.848
0.02
1.14
0.0E+00
0.0E+00

Runx2
6
0.811
0.053
1.13
0.0E+00
0.0E+00

Ccr2
6
0.777
0.066
1.12
0.0E+00
0.0E+00

Gnas
6
0.992
0.818
1.12
0.0E+00
0.0E+00

Selplg
6
0.983
0.576
1.12
0.0E+00
0.0E+00

Ifnar2
6
0.868
0.126
1.11
0.0E+00
0.0E+00

Cd68
6
0.83
0.039
1.11
0.0E+00
0.0E+00

Prkca
6
0.876
0.282
1.11
0.0E+00
0.0E+00

Npc2
6
0.98
0.605
1.11
0.0E+00
0.0E+00

Emp3
6
0.897
0.307
1.08
0.0E+00
0.0E+00

Fcrla
6
0.788
0.136
1.06
0.0E+00
0.0E+00

Stx7
6
0.897
0.213
1.05
0.0E+00
0.0E+00

Pkib
6
0.782
0.067
1.03
0.0E+00
0.0E+00

Neat1
6
0.848
0.362
1.02
0.0E+00
0.0E+00

Fam174a
6
0.85
0.187
1.02
0.0E+00
0.0E+00

Cd7
6
0.954
0.343
1.02
0.0E+00
0.0E+00

Lsp1
6
0.976
0.665
1.01
0.0E+00
0.0E+00

Fyb
6
0.944
0.401
1.01
0.0E+00
0.0E+00

Mef2c
6
0.947
0.263
1.01
0.0E+00
0.0E+00

Sub1
6
0.984
0.74
1.01
0.0E+00
0.0E+00

S100a6
6
0.895
0.158
1.00
0.0E+00
0.0E+00

Kctd12
6
0.81
0.113
1.00
0.0E+00
0.0E+00

Snx18
6
0.81
0.128
1.00
0.0E+00
0.0E+00

Pir
6
0.67
0.008
0.99
0.0E+00
0.0E+00

Trib1
6
0.722
0.066
0.98
0.0E+00
0.0E+00

Irf7
6
0.712
0.12
0.98
0.0E+00
0.0E+00

Kmo
6
0.79
0.042
0.98
0.0E+00
0.0E+00

Sec61b
6
0.985
0.67
0.97
0.0E+00
0.0E+00

Cst3
6
0.993
0.557
0.97
0.0E+00
0.0E+00

Ier5
6
0.919
0.474
0.97
0.0E+00
0.0E+00

Tubgcp5
6
0.744
0.043
0.97
0.0E+00
0.0E+00

Mbnl1
6
0.97
0.57
0.97
0.0E+00
0.0E+00

Abhd17b
6
0.78
0.158
0.97
0.0E+00
0.0E+00

Gltp
6
0.917
0.335
0.96
0.0E+00
0.0E+00

Spib
6
0.823
0.149
0.96
0.0E+00
0.0E+00

Sec61g
6
0.986
0.745
0.95
0.0E+00
0.0E+00

Amica1
6
0.791
0.117
0.95
0.0E+00
0.0E+00

Evi2a
6
0.768
0.135
0.95
0.0E+00
0.0E+00

Sh3bgr
6
0.7
0.008
0.95
0.0E+00
0.0E+00

Pacsin1
6
0.819
0.133
0.94
0.0E+00
0.0E+00

Lefty1
6
0.739
0.041
0.94
0.0E+00
0.0E+00

Ramp1
6
0.879
0.289
0.92
0.0E+00
0.0E+00

Plaur
6
0.561
0.064
0.91
0.0E+00
0.0E+00

Gm2a
6
0.91
0.303
0.91
0.0E+00
0.0E+00

H13
6
0.864
0.267
0.90
0.0E+00
0.0E+00

Zeb2
6
0.725
0.072
0.89
0.0E+00
0.0E+00

Cyth4
6
0.803
0.174
0.89
0.0E+00
0.0E+00

Hpse
6
0.73
0.079
0.89
0.0E+00
0.0E+00

Gapt
6
0.69
0.022
0.88
0.0E+00
0.0E+00

Reep5
6
0.918
0.409
0.88
0.0E+00
0.0E+00

Gsn
6
0.819
0.152
0.88
0.0E+00
0.0E+00

Rrbp1
6
0.798
0.202
0.87
0.0E+00
0.0E+00

Blnk
6
0.812
0.153
0.87
0.0E+00
0.0E+00

Hsp90b1
6
0.885
0.331
0.86
0.0E+00
0.0E+00

Ech1
6
0.843
0.285
0.86
0.0E+00
0.0E+00

H2-DMb1
6
0.711
0.133
0.86
0.0E+00
0.0E+00

Svbp
6
0.75
0.225
0.85
0.0E+00
0.0E+00

Ifnar1
6
0.758
0.199
0.84
0.0E+00
0.0E+00

Manf
6
0.913
0.432
0.84
0.0E+00
0.0E+00

Fyn
6
0.777
0.221
0.84
0.0E+00
0.0E+00

Tnfrsf13b
6
0.786
0.166
0.84
0.0E+00
0.0E+00

Ly86
6
0.733
0.109
0.83
0.0E+00
0.0E+00

Serinc3
6
0.867
0.317
0.83
0.0E+00
0.0E+00

Cd164
6
0.838
0.271
0.82
0.0E+00
0.0E+00

Tmem229b
6
0.706
0.069
0.82
0.0E+00
0.0E+00

Stk17b
6
0.859
0.565
0.82
0.0E+00
0.0E+00

Mtdh
6
0.863
0.382
0.81
0.0E+00
0.0E+00

Irf2bp2
6
0.712
0.106
0.81
0.0E+00
0.0E+00

Atp2a1
6
0.654
0.007
0.81
0.0E+00
0.0E+00

Slamf9
6
0.592
0.01
0.79
0.0E+00
0.0E+00

Ighm
6
0.993
0.397
0.77
0.0E+00
0.0E+00

Vimp
6
0.814
0.3
0.77
0.0E+00
0.0E+00

Klra17
6
0.57
0.007
0.76
0.0E+00
0.0E+00

I830077J02Rik
6
0.63
0.029
0.76
0.0E+00
0.0E+00

Fgfr1op2
6
0.822
0.264
0.76
0.0E+00
0.0E+00

Scimp
6
0.785
0.133
0.76
0.0E+00
0.0E+00

Ctsa
6
0.75
0.21
0.74
0.0E+00
0.0E+00

R3hdm4
6
0.798
0.291
0.74
0.0E+00
0.0E+00

Abhd17a
6
0.804
0.27
0.74
0.0E+00
0.0E+00

Smc6
6
0.845
0.457
0.73
0.0E+00
0.0E+00

Sla2
6
0.67
0.117
0.73
0.0E+00
0.0E+00

Ahnak
6
0.688
0.147
0.73
0.0E+00
0.0E+00

Litaf
6
0.728
0.186
0.72
0.0E+00
0.0E+00

Timp2
6
0.68
0.132
0.72
0.0E+00
0.0E+00

Gpcpd1
6
0.773
0.264
0.71
0.0E+00
0.0E+00

Edem2
6
0.687
0.145
0.71
0.0E+00
0.0E+00

Plekhm3
6
0.635
0.05
0.70
0.0E+00
0.0E+00

Slc44a2
6
0.713
0.154
0.70
0.0E+00
0.0E+00

Rnf149
6
0.601
0.122
0.70
0.0E+00
0.0E+00

Cdkn2d
6
0.703
0.203
0.69
0.0E+00
0.0E+00

Irf1
6
0.65
0.177
0.69
0.0E+00
0.0E+00

Rell1
6
0.586
0.052
0.68
0.0E+00
0.0E+00

Klk4
6
0.257
0.008
0.68
0.0E+00
0.0E+00

Fgr
6
0.623
0.049
0.68
0.0E+00
0.0E+00

Clec10a
6
0.48
0.007
0.68
0.0E+00
0.0E+00

Tbc1d8
6
0.593
0.025
0.67
0.0E+00
0.0E+00

Trim30a
6
0.597
0.087
0.66
0.0E+00
0.0E+00

Spns3
6
0.564
0.028
0.64
0.0E+00
0.0E+00

Lifr
6
0.543
0.012
0.64
0.0E+00
0.0E+00

Cd180
6
0.627
0.103
0.63
0.0E+00
0.0E+00

Rpgrip1
6
0.5
0.034
0.62
0.0E+00
0.0E+00

Csf2rb
6
0.577
0.039
0.62
0.0E+00
0.0E+00

Lag3
6
0.548
0.06
0.62
0.0E+00
0.0E+00

Tcf12
6
0.633
0.146
0.62
0.0E+00
0.0E+00

Rnf13
6
0.633
0.127
0.62
0.0E+00
0.0E+00

Ctse
6
0.673
0.213
0.61
0.0E+00
0.0E+00

Fam3c
6
0.678
0.188
0.60
0.0E+00
0.0E+00

Lpgat1
6
0.511
0.063
0.60
0.0E+00
0.0E+00

Rnf122
6
0.525
0.049
0.59
0.0E+00
0.0E+00

Sdc4
6
0.676
0.18
0.59
0.0E+00
0.0E+00

Klrd1
6
0.685
0.139
0.59
0.0E+00
0.0E+00

Havcr1
6
0.568
0.042
0.58
0.0E+00
0.0E+00

Nek6
6
0.518
0.025
0.58
0.0E+00
0.0E+00

Fcer1g
6
0.917
0.336
0.58
0.0E+00
0.0E+00

Card11
6
0.607
0.121
0.58
0.0E+00
0.0E+00

Hhex
6
0.553
0.093
0.58
0.0E+00
0.0E+00

Arhgef6
6
0.62
0.123
0.58
0.0E+00
0.0E+00

Mef2a
6
0.584
0.11
0.57
0.0E+00
0.0E+00

Rasgrp2
6
0.695
0.261
0.57
0.0E+00
0.0E+00

Sema4b
6
0.492
0.069
0.56
0.0E+00
0.0E+00

Mctp2
6
0.5
0.025
0.56
0.0E+00
0.0E+00

Csf2rb2
6
0.49
0.016
0.56
0.0E+00
0.0E+00

Paqr5
6
0.487
0.008
0.56
0.0E+00
0.0E+00

Rab33b
6
0.517
0.061
0.56
0.0E+00
0.0E+00

Hs3st1
6
0.551
0.071
0.55
0.0E+00
0.0E+00

Scpep1
6
0.564
0.094
0.55
0.0E+00
0.0E+00

Gpr137b
6
0.53
0.032
0.54
0.0E+00
0.0E+00

Cmah
6
0.546
0.084
0.54
0.0E+00
0.0E+00

Dntt
6
0.392
0.005
0.54
0.0E+00
0.0E+00

Man1a2
6
0.548
0.099
0.54
0.0E+00
0.0E+00

Adssl1
6
0.468
0.036
0.54
0.0E+00
0.0E+00

Flt3
6
0.51
0.043
0.54
0.0E+00
0.0E+00

Tgfbr1
6
0.52
0.086
0.54
0.0E+00
0.0E+00

Tex2
6
0.522
0.043
0.53
0.0E+00
0.0E+00

Atp13a2
6
0.507
0.046
0.53
0.0E+00
0.0E+00

Dirc2
6
0.493
0.029
0.53
0.0E+00
0.0E+00

Gas7
6
0.499
0.032
0.53
0.0E+00
0.0E+00

Net1
6
0.485
0.044
0.53
0.0E+00
0.0E+00

Npc1
6
0.484
0.029
0.53
0.0E+00
0.0E+00

Il10rb
6
0.59
0.14
0.52
0.0E+00
0.0E+00

Clec9a
6
0.445
0.01
0.52
0.0E+00
0.0E+00

Lgals3
6
0.756
0.26
0.52
0.0E+00
0.0E+00

Grina
6
0.578
0.145
0.51
0.0E+00
0.0E+00

Gna15
6
0.474
0.041
0.51
0.0E+00
0.0E+00

Cdh5
6
0.413
0.009
0.50
0.0E+00
0.0E+00

Ptprs
6
0.458
0.021
0.50
0.0E+00
0.0E+00

Mzb1
6
0.81
0.219
0.50
0.0E+00
0.0E+00

BC147527
6
0.456
0.026
0.49
0.0E+00
0.0E+00

Polr3gl
6
0.515
0.105
0.49
0.0E+00
0.0E+00

Ddr1
6
0.44
0.017
0.49
0.0E+00
0.0E+00

Rassf4
6
0.458
0.035
0.48
0.0E+00
0.0E+00

Fbxl13
6
0.435
0.004
0.48
0.0E+00
0.0E+00

Rgs18
6
0.443
0.034
0.47
0.0E+00
0.0E+00

Ccdc162
6
0.424
0.006
0.47
0.0E+00
0.0E+00

Ccr5
6
0.442
0.049
0.46
0.0E+00
0.0E+00

Nceh1
6
0.441
0.037
0.46
0.0E+00
0.0E+00

5430427O19Rik
6
0.417
0.042
0.46
0.0E+00
0.0E+00

Cd33
6
0.301
0.01
0.46
0.0E+00
0.0E+00

Cacna1e
6
0.409
0.013
0.45
0.0E+00
0.0E+00

B3gnt8
6
0.424
0.033
0.45
0.0E+00
0.0E+00

Stambpl1
6
0.433
0.054
0.45
0.0E+00
0.0E+00

Mycl
6
0.39
0.013
0.45
0.0E+00
0.0E+00

Tlr7
6
0.405
0.009
0.45
0.0E+00
0.0E+00

Slc29a3
6
0.424
0.024
0.45
0.0E+00
0.0E+00

Rilpl1
6
0.418
0.013
0.44
0.0E+00
0.0E+00

Lrrc16a
6
0.415
0.014
0.44
0.0E+00
0.0E+00

Eepd1
6
0.414
0.025
0.43
0.0E+00
0.0E+00

Klhl42
6
0.417
0.053
0.42
0.0E+00
0.0E+00

Tifab
6
0.393
0.019
0.41
0.0E+00
0.0E+00

Cd300lf
6
0.414
0.031
0.40
0.0E+00
0.0E+00

Pdzd4
6
0.368
0.004
0.39
0.0E+00
0.0E+00

Tnni2
6
0.416
0.038
0.39
0.0E+00
0.0E+00

Arhgap27os2
6
0.354
0.011
0.39
0.0E+00
0.0E+00

Tmem163
6
0.368
0.012
0.38
0.0E+00
0.0E+00

Tom1
6
0.391
0.036
0.38
0.0E+00
0.0E+00

Pirb
6
0.374
0.023
0.37
0.0E+00
0.0E+00

Zeb2os
6
0.351
0.014
0.37
0.0E+00
0.0E+00

Atp1a3
6
0.339
0.017
0.37
0.0E+00
0.0E+00

Rbm47
6
0.364
0.024
0.37
0.0E+00
0.0E+00

Tcf7l2
6
0.287
0.012
0.32
0.0E+00
0.0E+00

Plxdc1
6
0.295
0.007
0.31
0.0E+00
0.0E+00

Ldlrad3
6
0.291
0.009
0.31
0.0E+00
0.0E+00

Slco4a1
6
0.279
0.008
0.30
0.0E+00
0.0E+00

Pnck
6
0.268
0.005
0.29
0.0E+00
0.0E+00

P2ry13
6
0.246
0.004
0.28
0.0E+00
0.0E+00

P2ry6
6
0.277
0.01
0.28
0.0E+00
0.0E+00

Cpne2
6
0.273
0.012
0.28
0.0E+00
0.0E+00

Epha2
6
0.252
0.004
0.28
0.0E+00
0.0E+00

B3galnt1
6
0.258
0.005
0.27
0.0E+00
0.0E+00

Nbl1
6
0.256
0.01
0.27
0.0E+00
0.0E+00

Rap1a
6
0.94
0.466
0.90
1.3E−313
0.0E+00

9-Sep
6
0.721
0.272
0.60
5.6E−313
0.0E+00

Dclre1c
6
0.31
0.024
0.33
2.7E−312
5.2E−308

Ptpn6
6
0.892
0.426
0.89
2.0E−311
3.9E−307

Cd8a
6
0.436
0.084
0.78
2.9E−310
5.6E−306

Snx9
6
0.417
0.05
0.40
0.0E+00
8.7E−305

Ly6a
6
0.275
0.019
0.83
0.0E+00
1.1E−304

N4bp3
6
0.377
0.041
0.38
2.1E−307
4.1E−303

Cxxc5
6
0.58
0.135
0.54
3.6E−306
6.8E−302

Il7r
6
0.757
0.371
0.30
1.6E−305
3.1E−301

Asah1
6
0.433
0.053
0.42
1.5E−302
2.9E−298

Ftl1
6
0.999
0.963
0.91
1.2E−301
2.4E−297

Mgat1
6
0.589
0.125
0.54
1.4E−301
2.6E−297

Cd14
6
0.262
0.017
0.25
1.7E−301
3.3E−297

Itga4
6
0.716
0.214
0.69
1.8E−301
3.5E−297

Bloc1s2
6
0.739
0.189
0.71
1.8E−299
3.5E−295

Ifi44
6
0.248
0.011
0.35
1.6E−297
3.0E−293

Rab7b
6
0.24
0.011
0.28
2.9E−297
5.6E−293

Zfp691
6
0.281
0.021
0.32
1.9E−296
3.7E−292

Cib1
6
0.742
0.233
0.69
3.3E−295
6.3E−291

Zyx
6
0.623
0.157
0.61
3.3E−291
6.3E−287

Ubc
6
0.763
0.341
0.75
2.1E−290
4.0E−286

Rabgap1l
6
0.743
0.288
0.60
1.3E−289
2.6E−285

Trf
6
0.513
0.106
0.45
2.6E−289
4.9E−285

Gpr137b-ps
6
0.323
0.028
0.34
2.7E−289
5.1E−285

Eps15
6
0.53
0.119
0.47
2.5E−288
4.8E−284

Tgfb1
6
0.876
0.434
0.83
3.4E−288
6.6E−284

Gns
6
0.455
0.073
0.43
7.1E−288
1.4E−283

Mapkapk2
6
0.574
0.138
0.55
5.4E−286
1.0E−281

Adpgk
6
0.409
0.066
0.37
9.8E−286
1.9E−281

Tifa
6
0.409
0.056
0.44
7.0E−285
1.3E−280

Traf4
6
0.563
0.129
0.57
1.9E−284
3.7E−280

Gne
6
0.344
0.037
0.33
3.9E−284
7.6E−280

Cd44
6
0.609
0.148
0.58
9.1E−284
1.7E−279

Tbxa2r
6
0.312
0.044
0.32
2.9E−283
5.5E−279

Slc41a2
6
0.327
0.026
0.33
1.1E−280
2.0E−276

Fdps
6
0.637
0.156
0.80
1.1E−278
2.1E−274

Nptn
6
0.521
0.113
0.49
2.1E−276
4.0E−272

5730508B09Rik
6
0.29
0.026
0.31
3.7E−276
7.2E−272

Ifi44l
6
0.229
0.01
0.27
1.8E−275
3.6E−271

Lmo2
6
0.563
0.105
0.50
1.2E−274
2.4E−270

Xist
6
0.997
0.873
0.89
2.1E−274
4.0E−270

Arhgap17
6
0.597
0.156
0.54
3.9E−273
7.5E−269

Izumo1r
7
0.861
0.073
1.51
0.0E+00
0.0E+00

Trbc2
7
0.977
0.548
1.12
0.0E+00
0.0E+00

Cd3g
7
0.968
0.343
1.03
0.0E+00
0.0E+00

Trac
7
0.883
0.274
1.02
0.0E+00
0.0E+00

Cd3e
7
0.94
0.298
1.02
0.0E+00
0.0E+00

Cd3d
7
0.94
0.327
0.98
0.0E+00
0.0E+00

Rgs10
7
0.857
0.472
0.87
0.0E+00
0.0E+00

Tnfrsf4
7
0.47
0.038
0.80
0.0E+00
0.0E+00

Ifi27l2a
7
0.802
0.372
0.76
0.0E+00
0.0E+00

Lat
7
0.829
0.331
0.75
0.0E+00
0.0E+00

Tnfsf8
7
0.365
0.064
0.69
0.0E+00
0.0E+00

Lck
7
0.882
0.477
0.69
0.0E+00
0.0E+00

Ctla4
7
0.45
0.043
0.66
0.0E+00
0.0E+00

Cd28
7
0.704
0.207
0.66
0.0E+00
0.0E+00

Cd2
7
0.741
0.309
0.63
0.0E+00
0.0E+00

Pdcd1
7
0.336
0.037
0.63
0.0E+00
0.0E+00

Cd27
7
0.771
0.343
0.63
0.0E+00
0.0E+00

Sh2d1a
7
0.489
0.092
0.60
0.0E+00
0.0E+00

Cdk2ap2
7
0.863
0.601
0.56
0.0E+00
0.0E+00

Shisa5
7
0.991
0.872
0.54
0.0E+00
0.0E+00

Fyb
7
0.809
0.411
0.53
0.0E+00
0.0E+00

Maf
7
0.476
0.128
0.51
0.0E+00
0.0E+00

Cd6
7
0.494
0.09
0.50
0.0E+00
0.0E+00

Skap1
7
0.739
0.352
0.50
0.0E+00
0.0E+00

Cd5
7
0.459
0.081
0.49
0.0E+00
0.0E+00

Cd247
7
0.56
0.183
0.49
0.0E+00
0.0E+00

Tbc1d4
7
0.413
0.055
0.42
0.0E+00
0.0E+00

Hif1a
7
0.444
0.185
0.41
0.0E+00
0.0E+00

Cd4
7
0.485
0.145
0.38
2.3E−308
4.3E−304

Tox
7
0.435
0.155
0.38
3.5E−293
6.8E−289

Foxp3
7
0.174
0.01
0.25
1.0E−286
2.0E−282

Slamf6
7
0.506
0.215
0.42
1.8E−286
3.5E−282

Ccl5
8
0.993
0.181
2.74
0.0E+00
0.0E+00

Gzma
8
0.745
0.069
2.38
0.0E+00
0.0E+00

Nkg7
8
0.983
0.216
1.80
0.0E+00
0.0E+00

AW112010
8
0.996
0.569
1.52
0.0E+00
0.0E+00

Ncr1
8
0.951
0.125
1.42
0.0E+00
0.0E+00

Ctla2a
8
0.697
0.051
1.24
0.0E+00
0.0E+00

Klrd1
8
0.908
0.135
1.20
0.0E+00
0.0E+00

Ms4a4b
8
0.932
0.382
0.93
0.0E+00
0.0E+00

Klre1
8
0.703
0.016
0.93
0.0E+00
0.0E+00

Ccl3
8
0.426
0.063
0.92
0.0E+00
0.0E+00

Xcl1
8
0.532
0.077
0.90
0.0E+00
0.0E+00

Klrb1c
8
0.688
0.043
0.88
0.0E+00
0.0E+00

Klrc1
8
0.548
0.045
0.87
0.0E+00
0.0E+00

Il2rb
8
0.802
0.192
0.86
0.0E+00
0.0E+00

Klrk1
8
0.828
0.171
0.84
0.0E+00
0.0E+00

Klra3
8
0.455
0.011
0.83
0.0E+00
0.0E+00

Klri2
8
0.542
0.052
0.80
0.0E+00
0.0E+00

Serpinb9
8
0.596
0.116
0.79
0.0E+00
0.0E+00

Tyrobp
8
0.989
0.275
0.74
0.0E+00
0.0E+00

Vps37b
8
0.804
0.398
0.73
0.0E+00
0.0E+00

Ctsw
8
0.789
0.226
0.73
0.0E+00
0.0E+00

Gzmb
8
0.336
0.029
0.71
0.0E+00
0.0E+00

Eomes
8
0.578
0.021
0.71
0.0E+00
0.0E+00

Fcer1g
8
0.921
0.344
0.69
0.0E+00
0.0E+00

Ccl4
8
0.579
0.159
0.66
0.0E+00
0.0E+00

Serpinb6b
8
0.598
0.143
0.66
0.0E+00
0.0E+00

Ctsd
8
0.764
0.316
0.65
0.0E+00
0.0E+00

Nabp1
8
0.694
0.261
0.63
0.0E+00
0.0E+00

Gimap4
8
0.861
0.453
0.62
0.0E+00
0.0E+00

Ugcg
8
0.625
0.122
0.62
0.0E+00
0.0E+00

Fasl
8
0.552
0.061
0.59
0.0E+00
0.0E+00

Klra7
8
0.284
0.006
0.58
0.0E+00
0.0E+00

Dok2
8
0.648
0.192
0.57
0.0E+00
0.0E+00

Jak1
8
0.781
0.445
0.56
0.0E+00
0.0E+00

Klra9
8
0.364
0.005
0.56
0.0E+00
0.0E+00

Irf8
8
0.899
0.385
0.55
0.0E+00
0.0E+00

Klrc2
8
0.452
0.036
0.54
0.0E+00
0.0E+00

Sh2d2a
8
0.537
0.17
0.54
0.0E+00
0.0E+00

Ifngr1
8
0.833
0.423
0.51
0.0E+00
0.0E+00

Ctla2b
8
0.418
0.019
0.49
0.0E+00
0.0E+00

Klrb1f
8
0.491
0.089
0.48
0.0E+00
0.0E+00

Ccr2
8
0.475
0.092
0.46
0.0E+00
0.0E+00

Anxa2
8
0.625
0.16
0.46
0.0E+00
0.0E+00

Ptprc
8
0.904
0.632
0.46
0.0E+00
0.0E+00

Samd3
8
0.402
0.018
0.43
0.0E+00
0.0E+00

Ccr5
8
0.413
0.056
0.43
0.0E+00
0.0E+00

Pglyrp1
8
0.51
0.108
0.42
0.0E+00
0.0E+00

Klrb1a
8
0.338
0.026
0.40
0.0E+00
0.0E+00

Tm6sf1
8
0.404
0.07
0.36
0.0E+00
0.0E+00

Trdc
8
0.37
0.032
0.35
0.0E+00
0.0E+00

Ifitm10
8
0.339
0.016
0.35
0.0E+00
0.0E+00

Metrnl
8
0.325
0.037
0.35
0.0E+00
0.0E+00

1700025G04Rik
8
0.346
0.048
0.32
0.0E+00
0.0E+00

H2afz
8
0.965
0.731
0.32
0.0E+00
0.0E+00

Cma1
8
0.215
0.006
0.30
0.0E+00
0.0E+00

Prf1
8
0.232
0.011
0.28
0.0E+00
0.0E+00

Chsy1
8
0.33
0.056
0.30
7.6E−311
1.5E−306

Selplg
8
0.918
0.585
0.46
0.0E+00
4.6E−305

Cd7
8
0.779
0.361
0.56
2.7E−297
5.3E−293

Ahnak
8
0.519
0.164
0.37
4.3E−292
8.2E−288

Calm2
8
0.916
0.691
0.31
5.5E−284
1.1E−279

Txk
8
0.751
0.353
0.52
2.1E−278
4.0E−274

S100a10
8
0.899
0.574
0.47
6.0E−273
1.2E−268

Sh2d1a
8
0.438
0.1
0.38
8.2E−272
1.6E−267

Hmgb2
9
0.999
0.513
2.75
0.0E+00
0.0E+00

2810417H13Rik
9
0.919
0.038
2.64
0.0E+00
0.0E+00

Stmn1
9
0.977
0.103
2.49
0.0E+00
0.0E+00

Tuba1b
9
0.948
0.469
2.38
0.0E+00
0.0E+00

Tubb5
9
0.971
0.589
2.28
0.0E+00
0.0E+00

Ptma
9
1
0.958
2.21
0.0E+00
0.0E+00

H2afz
9
0.998
0.73
2.19
0.0E+00
0.0E+00

Ms4a1
9
0.995
0.178
2.07
0.0E+00
0.0E+00

H2afx
9
0.861
0.17
2.05
0.0E+00
0.0E+00

Hmgn2
9
0.99
0.328
2.03
0.0E+00
0.0E+00

Cd24a
9
0.976
0.187
1.92
0.0E+00
0.0E+00

Hmgn1
9
0.997
0.485
1.89
0.0E+00
0.0E+00

Cd79b
9
0.998
0.272
1.87
0.0E+00
0.0E+00

Ran
9
0.995
0.586
1.86
0.0E+00
0.0E+00

Nap1l1
9
0.997
0.432
1.85
0.0E+00
0.0E+00

Ighg1
9
0.891
0.111
1.84
0.0E+00
0.0E+00

Hmces
9
0.915
0.131
1.84
0.0E+00
0.0E+00

Hmgb1
9
0.995
0.764
1.83
0.0E+00
0.0E+00

Rgs13
9
0.948
0.065
1.83
0.0E+00
0.0E+00

Gapdh
9
0.998
0.746
1.83
0.0E+00
0.0E+00

Cd79a
9
0.997
0.232
1.81
0.0E+00
0.0E+00

Pou2af1
9
0.963
0.124
1.81
0.0E+00
0.0E+00

Anp32b
9
0.994
0.537
1.81
0.0E+00
0.0E+00

Mzb1
9
0.985
0.22
1.76
0.0E+00
0.0E+00

Cks2
9
0.807
0.116
1.74
0.0E+00
0.0E+00

Arpc5l
9
0.991
0.393
1.74
0.0E+00
0.0E+00

Vpreb3
9
0.894
0.128
1.69
0.0E+00
0.0E+00

Ebf1
9
0.987
0.193
1.69
0.0E+00
0.0E+00

Ube2s
9
0.947
0.464
1.66
0.0E+00
0.0E+00

H3f3a
9
1
0.925
1.64
0.0E+00
0.0E+00

Dut
9
0.883
0.181
1.63
0.0E+00
0.0E+00

Pold4
9
0.988
0.343
1.63
0.0E+00
0.0E+00

Slc25a5
9
0.997
0.7
1.62
0.0E+00
0.0E+00

H2afv
9
0.952
0.406
1.61
0.0E+00
0.0E+00

Txn1
9
0.987
0.501
1.60
0.0E+00
0.0E+00

Rbm3
9
0.999
0.819
1.59
0.0E+00
0.0E+00

Hnrnpa2b1
9
0.996
0.712
1.59
0.0E+00
0.0E+00

Chchd10
9
0.916
0.214
1.58
0.0E+00
0.0E+00

Crip1
9
0.997
0.578
1.58
0.0E+00
0.0E+00

Erh
9
0.985
0.542
1.56
0.0E+00
0.0E+00

Cks1b
9
0.843
0.066
1.55
0.0E+00
0.0E+00

Glrx3
9
0.971
0.316
1.54
0.0E+00
0.0E+00

Prdx1
9
0.994
0.646
1.53
0.0E+00
0.0E+00

Basp1
9
0.922
0.129
1.53
0.0E+00
0.0E+00

Ranbp1
9
0.927
0.449
1.53
0.0E+00
0.0E+00

Klhl6
9
0.934
0.239
1.52
0.0E+00
0.0E+00

Birc5
9
0.688
0.019
1.51
0.0E+00
0.0E+00

Tubb4b
9
0.79
0.249
1.50
0.0E+00
0.0E+00

Gcsam
9
0.874
0.055
1.50
0.0E+00
0.0E+00

Hnrnpa3
9
0.985
0.603
1.49
0.0E+00
0.0E+00

Cmpk1
9
0.929
0.319
1.47
0.0E+00
0.0E+00

Snrpe
9
0.993
0.614
1.47
0.0E+00
0.0E+00

2700094K13Rik
9
0.918
0.267
1.47
0.0E+00
0.0E+00

Rrm2
9
0.591
0.013
1.47
0.0E+00
0.0E+00

Slbp
9
0.89
0.299
1.47
0.0E+00
0.0E+00

Eaf2
9
0.9
0.061
1.46
0.0E+00
0.0E+00

Clic1
9
0.997
0.716
1.43
0.0E+00
0.0E+00

Pkig
9
0.934
0.231
1.43
0.0E+00
0.0E+00

Uchl3
9
0.922
0.226
1.42
0.0E+00
0.0E+00

Hnrnpk
9
0.994
0.73
1.42
0.0E+00
0.0E+00

Ube2c
9
0.546
0.017
1.42
0.0E+00
0.0E+00

Srsf3
9
0.991
0.627
1.41
0.0E+00
0.0E+00

Sypl
9
0.962
0.201
1.41
0.0E+00
0.0E+00

Snrpd1
9
0.95
0.327
1.40
0.0E+00
0.0E+00

Ppp1ca
9
0.993
0.734
1.40
0.0E+00
0.0E+00

Atp5b
9
0.99
0.727
1.40
0.0E+00
0.0E+00

Aicda
9
0.88
0.053
1.39
0.0E+00
0.0E+00

Top1
9
0.962
0.383
1.39
0.0E+00
0.0E+00

Dek
9
0.91
0.325
1.39
0.0E+00
0.0E+00

Lrmp
9
0.924
0.245
1.38
0.0E+00
0.0E+00

Snrpg
9
0.995
0.784
1.38
0.0E+00
0.0E+00

Hsp90aa1
9
0.976
0.629
1.37
0.0E+00
0.0E+00

Polr2g
9
0.938
0.316
1.37
0.0E+00
0.0E+00

Apitd1
9
0.894
0.08
1.36
0.0E+00
0.0E+00

Tnfrsf13c
9
0.906
0.147
1.35
0.0E+00
0.0E+00

Anp32e
9
0.9
0.249
1.35
0.0E+00
0.0E+00

Lmnb1
9
0.847
0.111
1.33
0.0E+00
0.0E+00

Gtf2a2
9
0.942
0.298
1.33
0.0E+00
0.0E+00

Top2a
9
0.667
0.023
1.32
0.0E+00
0.0E+00

H1fx
9
0.675
0.019
1.32
0.0E+00
0.0E+00

Cdc20
9
0.522
0.021
1.32
0.0E+00
0.0E+00

Psip1
9
0.918
0.232
1.32
0.0E+00
0.0E+00

Tcp1
9
0.955
0.36
1.32
0.0E+00
0.0E+00

Srsf2
9
0.962
0.554
1.32
0.0E+00
0.0E+00

Atp5a1
9
0.986
0.663
1.31
0.0E+00
0.0E+00

Mcm5
9
0.77
0.065
1.31
0.0E+00
0.0E+00

2700029M09Rik
9
0.883
0.183
1.31
0.0E+00
0.0E+00

Rhoh
9
0.969
0.478
1.30
0.0E+00
0.0E+00

Scimp
9
0.933
0.137
1.30
0.0E+00
0.0E+00

Bfsp2
9
0.775
0.057
1.30
0.0E+00
0.0E+00

Smagp
9
0.866
0.055
1.28
0.0E+00
0.0E+00

Cdca8
9
0.672
0.02
1.28
0.0E+00
0.0E+00

Hnrnpf
9
0.998
0.826
1.28
0.0E+00
0.0E+00

Dynll1
9
0.988
0.68
1.27
0.0E+00
0.0E+00

Ccnb2
9
0.623
0.013
1.27
0.0E+00
0.0E+00

Grb2
9
0.941
0.347
1.26
0.0E+00
0.0E+00

Pcna
9
0.759
0.171
1.26
0.0E+00
0.0E+00

Dbi
9
0.947
0.301
1.26
0.0E+00
0.0E+00

Rfc2
9
0.876
0.241
1.25
0.0E+00
0.0E+00

Snrpf
9
0.962
0.514
1.25
0.0E+00
0.0E+00

Calm3
9
0.938
0.429
1.25
0.0E+00
0.0E+00

Asf1b
9
0.75
0.034
1.24
0.0E+00
0.0E+00

Dnajc9
9
0.868
0.22
1.24
0.0E+00
0.0E+00

Lsm5
9
0.938
0.398
1.22
0.0E+00
0.0E+00

Snrpb
9
0.977
0.641
1.21
0.0E+00
0.0E+00

Mcm6
9
0.72
0.057
1.20
0.0E+00
0.0E+00

Srsf7
9
0.92
0.365
1.20
0.0E+00
0.0E+00

Pttg1
9
0.642
0.043
1.19
0.0E+00
0.0E+00

Tipin
9
0.781
0.103
1.19
0.0E+00
0.0E+00

Nudt21
9
0.94
0.338
1.19
0.0E+00
0.0E+00

Lsm6
9
0.926
0.337
1.19
0.0E+00
0.0E+00

Hnrnpu
9
0.916
0.399
1.18
0.0E+00
0.0E+00

Ube2d2a
9
0.981
0.56
1.18
0.0E+00
0.0E+00

Lsm4
9
0.927
0.417
1.18
0.0E+00
0.0E+00

Zfp706
9
0.956
0.492
1.16
0.0E+00
0.0E+00

Neil1
9
0.792
0.078
1.15
0.0E+00
0.0E+00

Alyref
9
0.807
0.21
1.15
0.0E+00
0.0E+00

Nusap1
9
0.568
0.009
1.15
0.0E+00
0.0E+00

Myl4
9
0.714
0.052
1.15
0.0E+00
0.0E+00

Smc4
9
0.795
0.286
1.15
0.0E+00
0.0E+00

Ube2n
9
0.94
0.393
1.13
0.0E+00
0.0E+00

Erp44
9
0.891
0.257
1.13
0.0E+00
0.0E+00

Ppp1cc
9
0.943
0.485
1.13
0.0E+00
0.0E+00

Lig1
9
0.693
0.056
1.12
0.0E+00
0.0E+00

U2af1
9
0.916
0.393
1.12
0.0E+00
0.0E+00

Tmpo
9
0.832
0.185
1.12
0.0E+00
0.0E+00

Ddx39
9
0.853
0.215
1.12
0.0E+00
0.0E+00

Vdac3
9
0.896
0.271
1.11
0.0E+00
0.0E+00

Mcm7
9
0.739
0.075
1.11
0.0E+00
0.0E+00

Ewsr1
9
0.923
0.386
1.11
0.0E+00
0.0E+00

Rbbp7
9
0.828
0.259
1.11
0.0E+00
0.0E+00

Sfpq
9
0.916
0.393
1.08
0.0E+00
0.0E+00

Bub3
9
0.841
0.301
1.08
0.0E+00
0.0E+00

Nasp
9
0.764
0.129
1.08
0.0E+00
0.0E+00

Csk
9
0.939
0.449
1.07
0.0E+00
0.0E+00

Mif4gd
9
0.887
0.301
1.07
0.0E+00
0.0E+00

Spc24
9
0.642
0.025
1.07
0.0E+00
0.0E+00

Mtf2
9
0.823
0.142
1.07
0.0E+00
0.0E+00

Tcf3
9
0.844
0.182
1.07
0.0E+00
0.0E+00

Mcm3
9
0.7
0.051
1.06
0.0E+00
0.0E+00

Iglc3
9
0.948
0.249
1.05
0.0E+00
0.0E+00

Gmnn
9
0.713
0.062
1.04
0.0E+00
0.0E+00

Nucks1
9
0.808
0.273
1.04
0.0E+00
0.0E+00

Ccna2
9
0.533
0.007
1.03
0.0E+00
0.0E+00

Dck
9
0.774
0.069
1.03
0.0E+00
0.0E+00

Phf5a
9
0.865
0.262
1.03
0.0E+00
0.0E+00

Dazap1
9
0.878
0.307
1.02
0.0E+00
0.0E+00

Hprt
9
0.862
0.329
1.02
0.0E+00
0.0E+00

Mki67
9
0.631
0.017
1.01
0.0E+00
0.0E+00

Bzw2
9
0.854
0.231
1.01
0.0E+00
0.0E+00

Ezh2
9
0.732
0.083
1.01
0.0E+00
0.0E+00

Akr1b3
9
0.896
0.396
0.99
0.0E+00
0.0E+00

Rbmxl1
9
0.802
0.187
0.99
0.0E+00
0.0E+00

Lsm3
9
0.838
0.251
0.99
0.0E+00
0.0E+00

Cdca3
9
0.597
0.013
0.98
0.0E+00
0.0E+00

Ssrp1
9
0.818
0.282
0.98
0.0E+00
0.0E+00

Lsm2
9
0.789
0.195
0.98
0.0E+00
0.0E+00

Tk1
9
0.631
0.02
0.98
0.0E+00
0.0E+00

Tmem243
9
0.86
0.28
0.97
0.0E+00
0.0E+00

Cdk1
9
0.53
0.01
0.97
0.0E+00
0.0E+00

Tcea1
9
0.848
0.264
0.97
0.0E+00
0.0E+00

Csrp2
9
0.742
0.043
0.96
0.0E+00
0.0E+00

Tra2b
9
0.956
0.568
0.96
0.0E+00
0.0E+00

Elof1
9
0.828
0.2
0.96
0.0E+00
0.0E+00

Apobec1
9
0.788
0.092
0.96
0.0E+00
0.0E+00

Mcm2
9
0.674
0.074
0.94
0.0E+00
0.0E+00

Cd19
9
0.801
0.106
0.94
0.0E+00
0.0E+00

Rfc1
9
0.765
0.125
0.94
0.0E+00
0.0E+00

Rbbp4
9
0.815
0.333
0.94
0.0E+00
0.0E+00

Sh2b2
9
0.724
0.061
0.91
0.0E+00
0.0E+00

H2-Ob
9
0.804
0.141
0.89
0.0E+00
0.0E+00

Rfc3
9
0.657
0.052
0.89
0.0E+00
0.0E+00

Rrm1
9
0.616
0.041
0.89
0.0E+00
0.0E+00

S1pr2
9
0.705
0.047
0.87
0.0E+00
0.0E+00

Dhfr
9
0.601
0.024
0.87
0.0E+00
0.0E+00

Cenpm
9
0.615
0.017
0.85
0.0E+00
0.0E+00

Lipc
9
0.66
0.032
0.83
0.0E+00
0.0E+00

Lbr
9
0.751
0.23
0.81
0.0E+00
0.0E+00

Igkc
9
1
0.693
0.77
0.0E+00
0.0E+00

Jchain
9
0.99
0.207
0.76
0.0E+00
0.0E+00

Tpx2
9
0.456
0.008
0.75
0.0E+00
0.0E+00

Mad2l1
9
0.605
0.035
0.74
0.0E+00
0.0E+00

Tacc3
9
0.565
0.018
0.73
0.0E+00
0.0E+00

Nuggc
9
0.586
0.026
0.72
0.0E+00
0.0E+00

Cenpe
9
0.459
0.008
0.71
0.0E+00
0.0E+00

Cep55
9
0.488
0.006
0.66
0.0E+00
0.0E+00

Fcmr
9
0.731
0.145
0.63
0.0E+00
0.0E+00

Ctsh
9
0.886
0.287
0.58
0.0E+00
0.0E+00

Esco2
9
0.388
0.003
0.58
0.0E+00
0.0E+00

Ncapg
9
0.47
0.01
0.58
0.0E+00
0.0E+00

Gpx1
9
0.887
0.572
0.46
0.0E+00
0.0E+00

Ftl1
9
0.999
0.964
0.44
0.0E+00
0.0E+00

Cyba
9
0.929
0.769
0.31
0.0E+00
0.0E+00

Lsp1
9
0.889
0.674
0.31
0.0E+00
0.0E+00

Dok3
9
0.723
0.102
0.87
1.0E−313
0.0E+00

Ssr4
9
0.754
0.529
0.27
1.2E−310
2.4E−306

Nono
9
0.919
0.408
1.01
0.0E+00
8.6E−305

Cdca2
9
0.411
0.008
0.60
0.0E+00
4.1E−304

Gdi2
9
0.987
0.532
1.35
5.2E−308
1.0E−303

Fen1
9
0.662
0.069
0.88
8.3E−308
1.6E−303

Xrcc1
9
0.709
0.093
0.82
6.1E−307
1.2E−302

Nedd8
9
0.981
0.604
1.18
1.4E−306
2.8E−302

Iglc2
9
0.847
0.209
0.97
2.8E−306
5.4E−302

Mybl2
9
0.417
0.005
0.59
6.4E−305
1.2E−300

Sumo2
9
0.99
0.781
1.30
8.3E−305
1.6E−300

Trp53i11
9
0.794
0.148
0.98
2.6E−304
5.0E−300

Mybl1
9
0.438
0.016
0.53
3.0E−304
5.7E−300

Cdkn3
9
0.425
0.008
0.74
3.1E−301
6.0E−297

Ybx1
9
0.998
0.788
1.62
1.7E−299
3.3E−295

Cd37
9
0.975
0.568
1.10
6.7E−299
1.3E−294

Cenpa
9
0.617
0.112
1.06
6.8E−297
1.3E−292

Cd22
9
0.642
0.079
0.72
1.4E−296
2.8E−292

Arhgap8
9
0.538
0.025
0.62
2.3E−295
4.4E−291

Aurkb
9
0.473
0.012
0.72
3.6E−295
6.9E−291

Atp5j
9
0.979
0.648
1.20
9.4E−294
1.8E−289

Mtmr14
9
0.771
0.099
1.00
1.2E−292
2.3E−288

Prim1
9
0.548
0.034
0.68
1.1E−289
2.2E−285

Ppp4r2
9
0.765
0.154
0.85
1.2E−289
2.2E−285

Rfc5
9
0.641
0.065
0.82
7.4E−289
1.4E−284

Pmf1
9
0.753
0.118
0.85
8.4E−289
1.6E−284

Arpp19
9
0.952
0.559
1.06
7.0E−286
1.4E−281

Hnrnpa1
9
0.985
0.616
1.36
2.1E−285
4.0E−281

H2afj
9
0.766
0.568
0.30
2.7E−285
5.2E−281

Atp5k
9
0.962
0.518
1.16
8.7E−285
1.7E−280

Ublcp1
9
0.695
0.116
0.83
2.8E−284
5.5E−280

Raly
9
0.94
0.526
1.03
7.7E−283
1.5E−278

Nuf2
9
0.38
0.004
0.52
1.3E−281
2.5E−277

Hist1h2ap
9
0.555
0.062
2.33
9.2E−281
1.8E−276

Cdc25b
9
0.565
0.056
0.71
3.8E−280
7.4E−276

H2-DMb2
9
0.98
0.275
1.39
2.0E−279
3.8E−275

Atp6v0e
9
0.84
0.619
0.38
4.1E−279
7.9E−275

Id3
9
0.722
0.112
1.01
5.2E−279
1.0E−274

Snrpa1
9
0.805
0.2
1.00
3.5E−278
6.8E−274

Uhrf1
9
0.502
0.016
0.72
6.8E−278
1.3E−273

Ccnb1
9
0.403
0.008
0.82
2.2E−277
4.3E−273

Cdk4
9
0.835
0.3
1.12
2.2E−276
4.3E−272

Racgap1
9
0.546
0.041
0.81
1.1E−275
2.1E−271

Set
9
0.936
0.524
1.22
8.7E−275
1.7E−270

Irf8
9
0.963
0.383
0.56
1.6E−274
3.1E−270

Smc2
9
0.594
0.061
0.84
3.3E−274
6.3E−270

Mbd4
9
0.529
0.033
0.58
2.0E−273
3.8E−269

Fignl1
9
0.394
0.007
0.44
3.5E−273
6.7E−269

Pbk
9
0.376
0.004
0.56
6.0E−273
1.1E−268

Polr1d
9
0.961
0.564
1.09
6.9E−273
1.3E−268

Atp5g2
9
0.991
0.741
1.31
8.6E−273
1.7E−268

Ucp2
9
0.996
0.747
1.40
1.0E−272
2.0E−268

Ckap2l
9
0.37
0.005
0.51
2.3E−272
4.4E−268

Hells
9
0.582
0.048
0.79
7.1E−272
1.4E−267

Ms4a1
10
0.991
0.178
1.67
0.0E+00
0.0E+00

Cd79b
10
0.995
0.273
1.67
0.0E+00
0.0E+00

Cd79a
10
0.998
0.232
1.51
0.0E+00
0.0E+00

Ebf1
10
0.992
0.193
1.40
0.0E+00
0.0E+00

Ighg1
10
0.844
0.114
1.39
0.0E+00
0.0E+00

Rgs13
10
0.907
0.068
1.31
0.0E+00
0.0E+00

Cd74
10
1
0.655
1.26
0.0E+00
0.0E+00

Pold4
10
0.973
0.344
1.24
0.0E+00
0.0E+00

Mzb1
10
0.97
0.221
1.23
0.0E+00
0.0E+00

H2-Eb1
10
0.999
0.43
1.16
0.0E+00
0.0E+00

H2-DMb2
10
0.971
0.276
1.15
0.0E+00
0.0E+00

Aicda
10
0.833
0.056
1.15
0.0E+00
0.0E+00

H2-Aa
10
0.999
0.472
1.14
0.0E+00
0.0E+00

Tnfrsf13c
10
0.864
0.149
1.11
0.0E+00
0.0E+00

Sypl
10
0.903
0.205
1.11
0.0E+00
0.0E+00

Crip1
10
0.982
0.579
1.10
0.0E+00
0.0E+00

Rhoh
10
0.96
0.479
1.04
0.0E+00
0.0E+00

H2-Ab1
10
0.995
0.505
1.02
0.0E+00
0.0E+00

Eaf2
10
0.798
0.067
1.00
0.0E+00
0.0E+00

Ifi30
10
0.922
0.288
1.00
0.0E+00
0.0E+00

Nap1l1
10
0.96
0.434
0.99
0.0E+00
0.0E+00

Arpc5l
10
0.944
0.396
0.99
0.0E+00
0.0E+00

Scimp
10
0.855
0.141
0.97
0.0E+00
0.0E+00

Cd37
10
0.965
0.569
0.95
0.0E+00
0.0E+00

Apoe
10
0.81
0.211
0.95
0.0E+00
0.0E+00

H2-DMa
10
0.934
0.319
0.94
0.0E+00
0.0E+00

Iglc1
10
0.827
0.204
0.93
0.0E+00
0.0E+00

Basp1
10
0.821
0.135
0.93
0.0E+00
0.0E+00

Pou2af1
10
0.84
0.131
0.91
0.0E+00
0.0E+00

Smim14
10
0.95
0.468
0.91
0.0E+00
0.0E+00

Hmces
10
0.8
0.138
0.90
0.0E+00
0.0E+00

Vpreb3
10
0.743
0.136
0.88
0.0E+00
0.0E+00

Bfsp2
10
0.649
0.063
0.83
0.0E+00
0.0E+00

Grb2
10
0.877
0.35
0.83
0.0E+00
0.0E+00

Mef2c
10
0.922
0.276
0.81
0.0E+00
0.0E+00

Klhl6
10
0.817
0.245
0.81
0.0E+00
0.0E+00

Zbtb20
10
0.829
0.314
0.78
0.0E+00
0.0E+00

Neil1
10
0.705
0.082
0.78
0.0E+00
0.0E+00

Erp44
10
0.801
0.262
0.78
0.0E+00
0.0E+00

Glrx3
10
0.828
0.324
0.77
0.0E+00
0.0E+00

Siglecg
10
0.794
0.164
0.77
0.0E+00
0.0E+00

H3f3a
10
0.999
0.926
0.77
0.0E+00
0.0E+00

Iglc2
10
0.825
0.21
0.76
0.0E+00
0.0E+00

Hvcn1
10
0.747
0.263
0.76
0.0E+00
0.0E+00

Smagp
10
0.691
0.064
0.76
0.0E+00
0.0E+00

Gcsam
10
0.674
0.065
0.75
0.0E+00
0.0E+00

Cd19
10
0.745
0.109
0.74
0.0E+00
0.0E+00

Pou2f2
10
0.792
0.215
0.74
0.0E+00
0.0E+00

Cfl1
10
0.998
0.94
0.73
0.0E+00
0.0E+00

Lrmp
10
0.797
0.252
0.73
0.0E+00
0.0E+00

Mif4gd
10
0.81
0.305
0.73
0.0E+00
0.0E+00

Cd24a
10
0.842
0.195
0.73
0.0E+00
0.0E+00

Lat2
10
0.763
0.194
0.71
0.0E+00
0.0E+00

H2-Ob
10
0.741
0.145
0.70
0.0E+00
0.0E+00

Hmgn1
10
0.924
0.489
0.69
0.0E+00
0.0E+00

Ube2d2a
10
0.897
0.564
0.69
0.0E+00
0.0E+00

Coro1a
10
0.989
0.879
0.68
0.0E+00
0.0E+00

S1pr2
10
0.602
0.053
0.68
0.0E+00
0.0E+00

Cd22
10
0.64
0.08
0.68
0.0E+00
0.0E+00

Plekho1
10
0.731
0.155
0.68
0.0E+00
0.0E+00

Apobec1
10
0.68
0.098
0.66
0.0E+00
0.0E+00

Pkig
10
0.788
0.239
0.66
0.0E+00
0.0E+00

Dynll1
10
0.958
0.682
0.66
0.0E+00
0.0E+00

Rftn1
10
0.768
0.266
0.64
0.0E+00
0.0E+00

Clic1
10
0.958
0.718
0.64
0.0E+00
0.0E+00

Arpc2
10
0.985
0.831
0.64
0.0E+00
0.0E+00

Lpxn
10
0.742
0.25
0.63
0.0E+00
0.0E+00

Trp53i11
10
0.64
0.156
0.63
0.0E+00
0.0E+00

Spib
10
0.706
0.166
0.62
0.0E+00
0.0E+00

Swap70
10
0.64
0.136
0.62
0.0E+00
0.0E+00

Fcmr
10
0.732
0.145
0.61
0.0E+00
0.0E+00

Lipc
10
0.523
0.039
0.60
0.0E+00
0.0E+00

Iglc3
10
0.89
0.252
0.59
0.0E+00
0.0E+00

Apitd1
10
0.641
0.093
0.58
0.0E+00
0.0E+00

Snx29
10
0.579
0.105
0.57
0.0E+00
0.0E+00

Sh2b2
10
0.575
0.069
0.55
0.0E+00
0.0E+00

Blnk
10
0.676
0.171
0.55
0.0E+00
0.0E+00

Mtf2
10
0.631
0.152
0.55
0.0E+00
0.0E+00

Dok3
10
0.602
0.108
0.55
0.0E+00
0.0E+00

Mtmr14
10
0.563
0.109
0.53
0.0E+00
0.0E+00

Dcaf12
10
0.632
0.17
0.52
0.0E+00
0.0E+00

Lyl1
10
0.529
0.083
0.50
0.0E+00
0.0E+00

Myl4
10
0.443
0.066
0.50
0.0E+00
0.0E+00

Slc25a19
10
0.533
0.108
0.50
0.0E+00
0.0E+00

Fcrl1
10
0.552
0.098
0.49
0.0E+00
0.0E+00

Srpk3
10
0.472
0.048
0.47
0.0E+00
0.0E+00

Nuggc
10
0.458
0.033
0.46
0.0E+00
0.0E+00

4930597A21Rik
10
0.395
0.049
0.45
0.0E+00
0.0E+00

Ildr1
10
0.404
0.035
0.42
0.0E+00
0.0E+00

Rab30
10
0.427
0.062
0.41
0.0E+00
0.0E+00

Cd86
10
0.448
0.068
0.40
0.0E+00
0.0E+00

Arhgap8
10
0.397
0.032
0.39
0.0E+00
0.0E+00

Csrp2
10
0.414
0.059
0.38
0.0E+00
0.0E+00

Mbd4
10
0.367
0.041
0.35
0.0E+00
0.0E+00

Tmem243
10
0.732
0.287
0.59
1.4E−312
2.9E−308

Anp32b
10
0.927
0.541
0.62
1.4E−310
2.8E−306

1-Mar
10
0.426
0.068
0.39
2.5E−307
4.9E−303

Efnb1
10
0.333
0.038
0.33
4.7E−307
9.0E−303

Cd83
10
0.773
0.277
0.76
1.9E−305
3.7E−301

Top1
10
0.831
0.389
0.63
1.1E−303
2.1E−299

Il4i1
10
0.417
0.065
0.62
1.0E−298
1.9E−294

Il21r
10
0.655
0.22
0.56
4.5E−298
8.7E−294

Gh
10
0.26
0.019
0.32
3.1E−297
6.0E−293

Mybl1
10
0.274
0.024
0.28
2.3E−292
4.5E−288

Eef2
10
0.998
0.945
0.64
1.6E−291
3.1E−287

Blk
10
0.474
0.09
0.41
1.8E−289
3.5E−285

Ublcp1
10
0.536
0.124
0.45
1.0E−288
1.9E−284

Bcar3
10
0.411
0.066
0.38
3.7E−287
7.2E−283

Pxk
10
0.515
0.122
0.44
1.5E−286
2.9E−282

Cd81
10
0.722
0.241
0.53
3.7E−286
7.1E−282

Ctsh
10
0.816
0.29
0.31
4.3E−284
8.3E−280

Zfos1
10
0.755
0.342
0.61
3.3E−283
6.3E−279

Eif3h
10
0.971
0.809
0.58
8.7E−283
1.7E−278

Dck
10
0.456
0.085
0.38
1.7E−282
3.3E−278

Csk
10
0.838
0.455
0.59
4.7E−282
9.0E−278

Bach2
10
0.449
0.086
0.40
2.3E−276
4.3E−272

Cd180
10
0.52
0.117
0.47
1.5E−274
2.9E−270

Xcl1
11
0.908
0.077
1.72
0.0E+00
0.0E+00

Ccl5
11
0.973
0.2
1.58
0.0E+00
0.0E+00

Ncr1
11
0.952
0.143
1.39
0.0E+00
0.0E+00

Nkg7
11
0.964
0.233
1.20
0.0E+00
0.0E+00

AW112010
11
0.997
0.578
1.19
0.0E+00
0.0E+00

Klrd1
11
0.853
0.154
1.00
0.0E+00
0.0E+00

Ctsw
11
0.906
0.235
0.97
0.0E+00
0.0E+00

Klrk1
11
0.88
0.184
0.95
0.0E+00
0.0E+00

Klrc1
11
0.595
0.055
0.92
0.0E+00
0.0E+00

Cd7
11
0.924
0.366
0.90
0.0E+00
0.0E+00

Gimap4
11
0.944
0.46
0.89
0.0E+00
0.0E+00

Ikzf2
11
0.759
0.211
0.87
0.0E+00
0.0E+00

Il2rb
11
0.779
0.207
0.78
0.0E+00
0.0E+00

Cd160
11
0.681
0.121
0.75
0.0E+00
0.0E+00

Gimap3
11
0.928
0.509
0.74
0.0E+00
0.0E+00

Fcer1g
11
0.966
0.356
0.69
0.0E+00
0.0E+00

Fasl
11
0.598
0.071
0.61
0.0E+00
0.0E+00

Klrc2
11
0.484
0.045
0.60
0.0E+00
0.0E+00

Klrb1f
11
0.579
0.095
0.60
0.0E+00
0.0E+00

Klrb1a
11
0.432
0.03
0.57
0.0E+00
0.0E+00

Hopx
11
0.493
0.044
0.51
0.0E+00
0.0E+00

Tyrobp
11
0.945
0.292
0.38
0.0E+00
0.0E+00

Serpinb6b
11
0.642
0.152
0.72
7.4E−288
1.4E−283

Car2
11
0.783
0.243
0.82
3.9E−283
7.4E−279

Bcl2a1d
11
0.643
0.165
0.61
1.2E−282
2.3E−278

Hcst
11
0.921
0.522
0.69
3.4E−276
6.5E−272

Klrb1c
11
0.484
0.063
0.56
1.2E−275
2.3E−271

Hes1
12
0.772
0.06
2.21
0.0E+00
0.0E+00

Lmo4
12
0.988
0.317
2.02
0.0E+00
0.0E+00

Hilpda
12
0.86
0.158
1.90
0.0E+00
0.0E+00

Calca
12
0.616
0.014
1.87
0.0E+00
0.0E+00

Il13
12
0.444
0.01
1.68
0.0E+00
0.0E+00

Gata3
12
0.946
0.128
1.68
0.0E+00
0.0E+00

Hs3st1
12
0.846
0.082
1.55
0.0E+00
0.0E+00

Areg
12
0.448
0.018
1.41
0.0E+00
0.0E+00

Tcrg-C1
12
0.786
0.108
1.34
0.0E+00
0.0E+00

Junb
12
0.989
0.749
1.28
0.0E+00
0.0E+00

Nfkb1
12
0.834
0.322
1.22
0.0E+00
0.0E+00

Nr4a1
12
0.894
0.376
1.16
0.0E+00
0.0E+00

Il4
12
0.546
0.018
1.13
0.0E+00
0.0E+00

Furin
12
0.662
0.153
1.11
0.0E+00
0.0E+00

Nfkbiz
12
0.813
0.236
1.03
0.0E+00
0.0E+00

Nrip1
12
0.878
0.319
0.99
0.0E+00
0.0E+00

Dnaja1
12
0.903
0.61
0.98
0.0E+00
0.0E+00

Samsn1
12
0.891
0.328
0.95
0.0E+00
0.0E+00

Spty2d1
12
0.618
0.157
0.94
0.0E+00
0.0E+00

Sptssa
12
0.903
0.481
0.94
0.0E+00
0.0E+00

Rora
12
0.788
0.189
0.92
0.0E+00
0.0E+00

Zfp36l1
12
0.956
0.604
0.92
0.0E+00
0.0E+00

Emb
12
0.926
0.443
0.89
0.0E+00
0.0E+00

Gpr65
12
0.758
0.174
0.83
0.0E+00
0.0E+00

H3f3b
12
0.997
0.953
0.76
0.0E+00
0.0E+00

Il17rb
12
0.643
0.013
0.76
0.0E+00
0.0E+00

Deptor
12
0.59
0.015
0.74
0.0E+00
0.0E+00

4930523C07Rik
12
0.769
0.416
0.72
0.0E+00
0.0E+00

Frmd4b
12
0.6
0.072
0.68
0.0E+00
0.0E+00

Itk
12
0.613
0.173
0.65
0.0E+00
0.0E+00

Epas1
12
0.605
0.055
0.64
0.0E+00
0.0E+00

1810011H11Rik
12
0.536
0.041
0.59
0.0E+00
0.0E+00

Homer2
12
0.446
0.007
0.54
0.0E+00
0.0E+00

AA467197
12
0.416
0.016
0.51
0.0E+00
0.0E+00

Ret
12
0.493
0.041
0.50
0.0E+00
0.0E+00

Ptpn13
12
0.431
0.009
0.50
0.0E+00
0.0E+00

Rxrg
12
0.232
0.001
0.26
2.1E−305
4.1E−301

Icos
12
0.637
0.135
0.70
2.1E−301
4.0E−297

Ccr4
12
0.304
0.009
0.37
5.9E−293
1.1E−288

Btg2
12
0.959
0.72
0.94
3.7E−291
7.0E−287

Rgs2
12
0.835
0.498
1.02
1.8E−283
3.5E−279

Vps37b
12
0.812
0.408
1.03
1.9E−282
3.7E−278

S100a4
14
0.928
0.154
2.33
0.0E+00
0.0E+00

S100a11
14
0.983
0.494
2.33
0.0E+00
0.0E+00

Mdh2
14
0.973
0.515
2.27
0.0E+00
0.0E+00

S100a6
14
0.953
0.191
2.25
0.0E+00
0.0E+00

Atox1
14
0.962
0.498
2.08
0.0E+00
0.0E+00

Cfp
14
0.908
0.056
1.98
0.0E+00
0.0E+00

Napsa
14
0.981
0.271
1.83
0.0E+00
0.0E+00

Cst3
14
0.989
0.577
1.81
0.0E+00
0.0E+00

Bcl2a1b
14
0.883
0.173
1.78
0.0E+00
0.0E+00

Gm2a
14
0.964
0.33
1.75
0.0E+00
0.0E+00

Gpx1
14
0.995
0.58
1.72
0.0E+00
0.0E+00

Vim
14
0.925
0.324
1.67
0.0E+00
0.0E+00

Rogdi
14
0.917
0.093
1.67
0.0E+00
0.0E+00

Spi1
14
0.934
0.146
1.66
0.0E+00
0.0E+00

Taldo1
14
0.962
0.506
1.61
0.0E+00
0.0E+00

Bcl2a1d
14
0.901
0.165
1.59
0.0E+00
0.0E+00

Tbc1d4
14
0.793
0.064
1.58
0.0E+00
0.0E+00

Gsn
14
0.909
0.181
1.55
0.0E+00
0.0E+00

Lsp1
14
0.992
0.679
1.46
0.0E+00
0.0E+00

Grasp
14
0.723
0.059
1.44
0.0E+00
0.0E+00

Vasp
14
0.964
0.614
1.43
0.0E+00
0.0E+00

Ppp1r14a
14
0.718
0.009
1.40
0.0E+00
0.0E+00

Pglyrp1
14
0.786
0.116
1.39
0.0E+00
0.0E+00

Ms4a6c
14
0.861
0.085
1.36
0.0E+00
0.0E+00

Il1r2
14
0.603
0.016
1.34
0.0E+00
0.0E+00

Plbd1
14
0.833
0.051
1.33
0.0E+00
0.0E+00

Ywhah
14
0.915
0.429
1.29
0.0E+00
0.0E+00

Avpi1
14
0.787
0.086
1.26
0.0E+00
0.0E+00

Efhd2
14
0.839
0.215
1.10
0.0E+00
0.0E+00

Tctex1d2
14
0.792
0.104
1.07
0.0E+00
0.0E+00

Snx20
14
0.801
0.19
1.04
0.0E+00
0.0E+00

M6pr
14
0.854
0.333
1.03
0.0E+00
0.0E+00

Cyp4f16
14
0.671
0.075
1.02
0.0E+00
0.0E+00

Fam105a
14
0.776
0.194
0.98
0.0E+00
0.0E+00

Pak1
14
0.598
0.015
0.80
0.0E+00
0.0E+00

Clec4a2
14
0.512
0.009
0.77
3.5E−303
6.7E−299

2900052N01Rik
14
0.433
0.004
0.63
5.0E−302
9.6E−298

Bcl2a1a
14
0.66
0.031
1.28
6.0E−298
1.1E−293

Arpc1b
14
0.995
0.846
1.35
8.5E−295
1.6E−290

Ostf1
14
0.945
0.586
1.11
3.3E−293
6.3E−289

H2-Eb1
14
0.994
0.447
2.18
7.1E−289
1.4E−284

Btg2
14
0.984
0.722
1.34
6.3E−288
1.2E−283

Rel
14
0.826
0.204
1.14
1.3E−286
2.5E−282

Wdfy4
14
0.742
0.062
0.92
2.6E−285
5.0E−281

Mkrn1
14
0.833
0.344
0.93
3.3E−281
6.4E−277

Anpep
14
0.51
0.012
0.65

l.0E−277
2.0E−273

Ccnd1
14
0.651
0.052
1.13
2.8E−275
5.4E−271

H2-Ab1
14
0.995
0.519
2.12
1.7E−271
3.2E−267

Cd7
17
0.988
0.375
2.02
0.0E+00
0.0E+00

Cd160
17
0.924
0.128
1.50
0.0E+00
0.0E+00

Dapk2
17
0.786
0.067
1.16
0.0E+00
0.0E+00

Ctsw
17
0.956
0.246
1.26
3.1E−308
6.0E−304

Cd3g
17
0.83
0.377
1.58
8.6E−307
1.7E−302

Igha
20
0.924
0.291
6.73
0.0E+00
0.0E+00

Igkc
20
0.996
0.706
5.98
0.0E+00
0.0E+00

Jchain
20
0.996
0.239
5.84
0.0E+00
0.0E+00

Iglv1
20
0.75
0.034
3.48
0.0E+00
0.0E+00

Mzb1
20
0.962
0.251
3.03
0.0E+00
0.0E+00

Txndc5
20
0.873
0.188
2.71
0.0E+00
0.0E+00

Hsp90b1
20
0.907
0.362
2.68
0.0E+00
0.0E+00

Ssr4
20
0.919
0.537
2.39
0.0E+00
0.0E+00

Sec11c
20
0.928
0.538
2.19
0.0E+00
0.0E+00

Pdia4
20
0.839
0.186
2.11
0.0E+00
0.0E+00

Xbp1
20
0.86
0.268
2.07
0.0E+00
0.0E+00

Edem1
20
0.843
0.167
2.04
0.0E+00
0.0E+00

Manf
20
0.898
0.459
1.99
0.0E+00
0.0E+00

H13
20
0.869
0.301
1.94
0.0E+00
0.0E+00

Spcs1
20
0.886
0.484
1.78
0.0E+00
0.0E+00

Ppib
20
0.877
0.627
1.76
0.0E+00
0.0E+00

Sdf2l1
20
0.843
0.194
1.76
0.0E+00
0.0E+00

Sec61b
20
0.915
0.688
1.75
0.0E+00
0.0E+00

Pdia6
20
0.852
0.332
1.73
0.0E+00
0.0E+00

Derl3
20
0.805
0.017
1.70
0.0E+00
0.0E+00

Hspa5
20
0.86
0.503
1.68
0.0E+00
0.0E+00

Calr
20
0.881
0.524
1.67
0.0E+00
0.0E+00

Fkbp2
20
0.835
0.201
1.64
0.0E+00
0.0E+00

Rexo2
20
0.839
0.387
1.63
0.0E+00
0.0E+00

Edem2
20
0.835
0.174
1.62
0.0E+00
0.0E+00

Prdx4
20
0.771
0.085
1.60
0.0E+00
0.0E+00

Spcs2
20
0.898
0.599
1.60
0.0E+00
0.0E+00

Krtcap2
20
0.898
0.556
1.58
0.0E+00
0.0E+00

Creld2
20
0.767
0.128
1.55
0.0E+00
0.0E+00

Trp53inp1
20
0.746
0.115
1.49
0.0E+00
0.0E+00

Txndc11
20
0.792
0.136
1.46
0.0E+00
0.0E+00

Selk
20
0.877
0.596
1.41
0.0E+00
0.0E+00

Lman1
20
0.788
0.098
1.40
0.0E+00
0.0E+00

Dnajc3
20
0.784
0.268
1.38
0.0E+00
0.0E+00

Dnajb11
20
0.78
0.252
1.38
0.0E+00
0.0E+00

Srp9
20
0.869
0.534
1.34
0.0E+00
0.0E+00

Ssr2
20
0.805
0.325
1.33
0.0E+00
0.0E+00

Tmed10
20
0.86
0.388
1.30
0.0E+00
0.0E+00

Ddost
20
0.788
0.314
1.29
0.0E+00
0.0E+00

Ckap4
20
0.754
0.012
1.28
0.0E+00
0.0E+00

Ndufa1
20
0.814
0.502
1.27
0.0E+00
0.0E+00

Ssr3
20
0.754
0.207
1.24
0.0E+00
0.0E+00

Clptm1l
20
0.763
0.227
1.15
0.0E+00
0.0E+00

Ift20
20
0.763
0.283
1.14
0.0E+00
0.0E+00

Tmem248
20
0.703
0.148
0.92
0.0E+00
0.0E+00

Tnfrsf17
20
0.61
0.001
1.41
1.9E−307
3.6E−303

Spcs3
20
0.758
0.185
1.12
9.6E−307
1.9E−302

Cope
20
0.826
0.417
1.15
2.0E−303
3.8E−299

Fkbp11
20
0.682
0.005
1.36
3.1E−301
5.9E−297

Ccr10
20
0.602
0.001
1.39
1.6E−297
3.2E−293

Serp1
20
0.898
0.545
1.64
1.1E−290
2.1E−286

Derl1
20
0.733
0.292
1.00
1.4E−289
2.7E−285

Sdc1
20
0.729
0.062
1.25
1.1E−283
2.1E−279

Rpn2
20
0.75
0.306
1.13
4.4E−280
8.4E−276

Reep5
20
0.826
0.438
1.30
3.1E−279
6.0E−275

Slc35b1
20
0.674
0.133
0.96
3.3E−279
6.3E−275

Sec61g
20
0.881
0.759
1.35
1.3E−277
2.5E−273

Iglc2
20
0.907
0.234
3.07
1.0E−274
2.0E−270

Cst3
21
1
0.582
4.06
0.0E+00
0.0E+00

Ppt1
21
0.897
0.177
2.41
0.0E+00
0.0E+00

Vim
21
0.979
0.331
2.29
0.0E+00
0.0E+00

H2-DMb1
21
0.987
0.164
2.27
0.0E+00
0.0E+00

Naaa
21
0.838
0.034
2.27
0.0E+00
0.0E+00

Atox1
21
0.983
0.503
2.11
0.0E+00
0.0E+00

Fuca1
21
0.859
0.231
1.38
0.0E+00
0.0E+00

Cxx1a
21
0.778
0.09
1.28
4.7E−286
9.0E−282

Psmb9
21
0.944
0.441
1.57
3.6E−280
7.0E−276

Fgd2
21
0.876
0.051
1.29
2.8E−277
5.3E−273

Aif1
21
0.915
0.05
1.96
2.5E−274
4.8E−270

Lyz2
22
0.991
0.073
4.40
0.0E+00
0.0E+00

Ifitm3
22
0.961
0.058
2.97
0.0E+00
0.0E+00

Cebpb
22
0.953
0.256
2.44
0.0E+00
0.0E+00

Lst1
22
0.953
0.146
2.34
0.0E+00
0.0E+00

Psap
22
1
0.531
2.07
0.0E+00
0.0E+00

Ms4a6c
22
0.935
0.093
2.01
0.0E+00
0.0E+00

Ctss
22
0.957
0.391
1.80
0.0E+00
0.0E+00

Mafb
22
0.75
0.008
1.77
0.0E+00
0.0E+00

Msrb1
22
0.875
0.206
1.75
0.0E+00
0.0E+00

Sat1
22
0.953
0.458
1.67
0.0E+00
0.0E+00

Prdx5
22
0.901
0.466
1.59
0.0E+00
0.0E+00

Csf1r
22
0.832
0.007
1.31
0.0E+00
0.0E+00

Clec4a3
22
0.776
0.005
1.27
0.0E+00
0.0E+00

Ccl6
22
0.836
0.019
1.92
3.9E−305
7.5E−301

Ccl9
22
0.728
0.007
1.71
5.0E−293
9.6E−289

Sirpb1b
22
0.724
0.006
1.05
5.7E−293
1.1E−288

Sirpb1c
22
0.741
0.008
1.08
4.9E−289
9.4E−285

Lamp1
22
0.931
0.485
1.34
6.3E−288
1.2E−283

Clec4a1
22
0.69
0.006
1.00
1.4E−282
2.7E−278

Fscn1
24
0.883
0.029
2.62
0.0E+00
0.0E+00

Ccr7
24
0.906
0.302
2.44
0.0E+00
0.0E+00

Tbc1d4
24
0.928
0.071
2.07
0.0E+00
0.0E+00

Tmem123
24
0.924
0.376
1.83
0.0E+00
0.0E+00

Marcks
24
0.919
0.076
1.66
0.0E+00
0.0E+00

Tspan3
24
0.78
0.09
1.54
0.0E+00
0.0E+00

Lamp1
24
0.933
0.485
1.48
0.0E+00
0.0E+00

Ogfrl1
24
0.861
0.094
1.46
0.0E+00
0.0E+00

Iscu
24
0.915
0.32
1.44
0.0E+00
0.0E+00

Relb
24
0.924
0.189
1.43
0.0E+00
0.0E+00

Cacnb3
24
0.771
0.004
1.14
0.0E+00
0.0E+00

Birc2
24
0.78
0.101
1.09
0.0E+00
0.0E+00

Tmcc3
24
0.812
0.049
1.19
4.7E−307
9.1E−303

Marcksl1
24
0.951
0.177
2.06
1.0E−297
1.9E−293

Traf1
24
0.906
0.328
1.53
2.2E−294
4.3E−290

Cxcl16
24
0.839
0.026
1.73
1.3E−285
2.6E−281

Igfbp7
25
0.982
0.079
3.30
0.0E+00
0.0E+00

Fabp4
25
0.937
0.006
2.63
0.0E+00
0.0E+00

Plvap
25
0.878
0.01
2.31
0.0E+00
0.0E+00

Tm4sf1
25
0.869
0.003
1.92
0.0E+00
0.0E+00

Ramp2
25
0.819
0.004
1.53
0.0E+00
0.0E+00

Egfl7
25
0.837
0.004
1.30
0.0E+00
0.0E+00

Esam
25
0.801
0.007
1.27
0.0E+00
0.0E+00

Cav1
25
0.729
0.003
1.15
0.0E+00
0.0E+00

Flt1
25
0.783
0.002
1.11
0.0E+00
0.0E+00

Emcn
25
0.692
0.001
1.02
0.0E+00
0.0E+00

Crip2
25
0.792
0.019
1.22
6.3E−311
1.2E−306

Apold1
25
0.715
0.004
1.47
0.0E+00
1.1E−304

Ifitm3
25
0.95
0.059
2.03
2.1E−299
4.0E−295

Mgll
25
0.706
0.021
1.07
1.9E−296
3.6E−292

Ecscr
25
0.674
0.004
0.97
5.8E−291
1.1E−286

Tmem252
25
0.584
0.001
1.19
4.8E−282
9.2E−278

Ptprb
25
0.597
0.002
0.82
1.5E−279
2.8E−275

Mcpt1
26
0.899
0.071
6.05
0.0E+00
0.0E+00

Mcpt2
26
0.894
0.041
5.51
0.0E+00
0.0E+00

Ifitm1
26
0.991
0.034
3.82
0.0E+00
0.0E+00

Cpa3
26
0.991
0.011
3.73
0.0E+00
0.0E+00

Cd63
26
0.991
0.053
3.36
0.0E+00
0.0E+00

Fcer1a
26
0.982
0.008
3.13
0.0E+00
0.0E+00

Mcpt4
26
0.77
0.003
3.06
0.0E+00
0.0E+00

Ifitm2
26
0.986
0.085
2.80
0.0E+00
0.0E+00

Ier3
26
0.862
0.035
2.58
0.0E+00
0.0E+00

Prnp
26
0.899
0.028
2.47
0.0E+00
0.0E+00

Tph1
26
0.889
0.005
2.46
0.0E+00
0.0E+00

Furin
26
0.834
0.161
1.99
0.0E+00
0.0E+00

Scin
26
0.899
0.005
1.97
0.0E+00
0.0E+00

Srgn
26
1
0.784
1.94
0.0E+00
0.0E+00

Cyp11a1
26
0.917
0.004
1.90
0.0E+00
0.0E+00

Ms4a2
26
0.889
0.002
1.86
0.0E+00
0.0E+00

Gata2
26
0.866
0.004
1.76
0.0E+00
0.0E+00

Cmtm7
26
0.972
0.323
1.53
0.0E+00
0.0E+00

Cd34
26
0.876
0.008
1.44
0.0E+00
0.0E+00

Gmpr
26
0.857
0.005
1.36
0.0E+00
0.0E+00

Itga2b
26
0.719
0.003
1.10
0.0E+00
0.0E+00

Car8
26
0.677
0.002
0.95
1.5E−301
2.9E−297

Npl
26
0.742
0.02
1.14
3.3E−300
6.3E−296

Cx3cr1
26
0.783
0.009
1.11
3.8E−283
7.2E−279

Mcpt9
26
0.59
0.002
2.54
1.2E−275
2.4E−271

Gpx4
26
0.968
0.673
1.37
2.7E−274
5.3E−270

Il1rl1
26
0.724
0.007
0.96
7.9E−274
1.5E−269

Fabp2
30
0.963
0.058
5.36
0.0E+00
0.0E+00

Fabp1
30
0.904
0.029
4.81
0.0E+00
0.0E+00

Rbp2
30
0.926
0.017
4.50
0.0E+00
0.0E+00

Aldob
30
0.956
0.014
3.33
0.0E+00
0.0E+00

Crip1
30
0.978
0.596
2.94
0.0E+00
0.0E+00

Lgals4
30
0.993
0.026
2.92
0.0E+00
0.0E+00

2200002D01Rik
30
0.933
0.029
2.77
0.0E+00
0.0E+00

Dstn
30
0.956
0.14
2.44
0.0E+00
0.0E+00

Cystm1
30
0.919
0.028
2.39
0.0E+00
0.0E+00

Fth1
30
0.993
0.98
2.31
0.0E+00
0.0E+00

Txn1
30
0.97
0.522
2.24
0.0E+00
0.0E+00

Scp2
30
0.933
0.593
2.18
0.0E+00
0.0E+00

Smim24
30
0.83
0.069
2.15
0.0E+00
0.0E+00

Dbi
30
0.941
0.329
2.08
0.0E+00
0.0E+00

Mdh1
30
0.919
0.505
1.89
0.0E+00
0.0E+00

Atpif1
30
0.919
0.359
1.86
0.0E+00
0.0E+00

Prdx1
30
0.941
0.662
1.79
0.0E+00
0.0E+00

Hadh
30
0.859
0.137
1.79
0.0E+00
0.0E+00

Cyb5r3
30
0.778
0.178
1.74
0.0E+00
0.0E+00

Cyb5a
30
0.874
0.382
1.70
0.0E+00
0.0E+00

Cbr1
30
0.77
0.109
1.65
0.0E+00
0.0E+00

Cycs
30
0.889
0.505
1.65
0.0E+00
0.0E+00

Slc9a3r1
30
0.867
0.407
1.57
0.0E+00
0.0E+00

Glrx
30
0.8
0.123
1.55
0.0E+00
0.0E+00

Atp5o
30
0.859
0.559
1.46
0.0E+00
0.0E+00

Rfk
30
0.77
0.126
1.43
0.0E+00
0.0E+00

Txndc17
30
0.83
0.327
1.39
0.0E+00
0.0E+00

Pepd
30
0.711
0.11
1.24
0.0E+00
0.0E+00

Edf1
30
0.926
0.649
1.38
1.8E−310
3.6E−306

Phgr1
30
0.926
0.008
2.86
0.0E+00
2.9E−305

Acaa1a
30
0.733
0.153
1.17
0.0E+00
9.2E−305

Cndp2
30
0.659
0.125
1.16
1.2E−307
2.3E−303

Mdh2
30
0.889
0.522
1.78
4.5E−305
8.6E−301

Cox5a
30
0.933
0.594
1.41
8.4E−297
1.6E−292

Slc25a5
30
0.941
0.713
1.60
4.3E−293
8.3E−289

Atp5j2
30
0.933
0.746
1.31
4.8E−290
9.2E−286

Uqcrq
30
0.911
0.569
1.36
8.3E−288
1.6E−283

Abhd11os
30
0.852
0.003
1.59
1.5E−281
2.9E−277

Krt20
30
0.844
0.004
2.03
5.4E−280
1.0E−275

Ckmt1
30
0.837
0.005
2.24
4.6E−279
8.8E−275

Sephs2
30
0.741
0.16
1.17
5.4E−277
1.0E−272

Prap1
30
0.852
0.005
2.71
6.4E−276
1.2E−271

Calml4
30
0.852
0.005
1.72
8.0E−275
1.5E−270

Uqcrb
30
0.889
0.585
1.33
8.6E−274
1.7E−269

Cst3
31
0.978
0.583
2.21
0.0E+00
0.0E+00

Epsti1
31
0.425
0.174
1.60
0.0E+00
0.0E+00

Ccl21a
33
0.695
0.036
5.74
0.0E+00
0.0E+00

Mfge8
33
0.952
0.048
3.74
0.0E+00
0.0E+00

Igfbp7
33
0.981
0.082
3.64
1.8E−272
3.4E−268

Oat
35
0.717
0.164
2.24
0.0E+00
0.0E+00

Spint2
35
0.869
0.365
2.15
8.8E−311
1.7E−306

Msrb1
36
0.989
0.208
2.03
0.0E+00
0.0E+00

Mif
37
1
0.593
2.36
1.2E−276
2.3E−272

Defa24
39
0.328
0.068
7.77
0.0E+00
0.0E+00

Itln1
39
0.344
0.027
5.40
0.0E+00
0.0E+00

TABLE 2

Differential expression analysis between pairs of clusters in PP regions, related to FIG. 1. In certain

embodiments, the genes can be used as markers for the cell types represented by each cluster. The table

disclosed here represents only the genes with adjusted p values of 0 or less than or equal to 1.0E−150

and the genes were expressed in greater than 50% of cell type 1 and less than 10% of cell type 2.

cluster ID
cluster ID
percentage of
percentage of

of cell
of cell
expressing cells
expressing cells
LN (average

p value,

gene
type 1
type 2
in cell type 1
in cell type 2
fold change)
p value
adjusted

Ms4a4b
1
2
0.884
0.074
1.28E+00
0.00E+00
0.00E+00

Trbc1
1
2
0.612
0.061
1.26E+00
0.00E+00
0.00E+00

Cd3g
1
2
0.907
0.052
1.26E+00
0.00E+00
0.00E+00

Igfbp4
1
2
0.632
0.03
1.23E+00
0.00E+00
0.00E+00

Cd3d
1
2
0.892
0.073
1.19E+00
0.00E+00
0.00E+00

Trac
1
2
0.803
0.034
1.09E+00
0.00E+00
0.00E+00

Cd3e
1
2
0.846
0.057
1.09E+00
0.00E+00
0.00E+00

Lef1
1
2
0.804
0.046
1.09E+00
0.00E+00
0.00E+00

Lat
1
2
0.755
0.055
8.95E−01
0.00E+00
0.00E+00

Skap1
1
2
0.674
0.038
7.44E−01
0.00E+00
0.00E+00

Fyb
1
2
0.646
0.05
7.11E−01
0.00E+00
0.00E+00

Thy1
1
2
0.546
0.033
6.87E−01
0.00E+00
0.00E+00

Tcf7
1
2
0.531
0.026
5.85E−01
0.00E+00
0.00E+00

Txk
1
2
0.509
0.032
5.65E−01
0.00E+00
0.00E+00

Igfbp4
1
3
0.632
0.022
1.23E+00
0.00E+00
0.00E+00

Ms4a4b
1
3
0.884
0.088
1.22E+00
0.00E+00
0.00E+00

Cd3d
1
3
0.892
0.031
1.22E+00
0.00E+00
0.00E+00

Cd3g
1
3
0.907
0.081
1.12E+00
0.00E+00
0.00E+00

Trac
1
3
0.803
0.062
1.06E+00
0.00E+00
0.00E+00

Cd3e
1
3
0.846
0.047
1.01E+00
0.00E+00
0.00E+00

Ccr7
1
3
0.617
0.03
8.61E−01
0.00E+00
0.00E+00

Ifi27l2a
1
3
0.578
0.043
8.38E−01
0.00E+00
0.00E+00

Cd2
1
3
0.651
0.023
7.46E−01
0.00E+00
0.00E+00

Cd27
1
3
0.632
0.097
6.41E−01
0.00E+00
0.00E+00

Emp3
1
3
0.56
0.076
5.74E−01
0.00E+00
0.00E+00

Sell
1
3
0.548
0.064
5.65E−01
0.00E+00
0.00E+00

Ms4a4b
1
4
0.884
0.027
1.33E+00
0.00E+00
0.00E+00

Cd3g
1
4
0.907
0.032
1.25E+00
0.00E+00
0.00E+00

Cd3d
1
4
0.892
0.016
1.24E+00
0.00E+00
0.00E+00

Igfbp4
1
4
0.632
0.09
1.14E+00
0.00E+00
0.00E+00

Cd3e
1
4
0.846
0.012
1.12E+00
0.00E+00
0.00E+00

Trac
1
4
0.803
0.012
1.11E+00
0.00E+00
0.00E+00

Lef1
1
4
0.804
0.029
1.10E+00
0.00E+00
0.00E+00

Ms4a6b
1
4
0.745
0.027
9.17E−01
0.00E+00
0.00E+00

Ifi27l2a
1
4
0.578
0.038
8.50E−01
0.00E+00
0.00E+00

Ccr7
1
4
0.617
0.066
8.01E−01
0.00E+00
0.00E+00

Cd2
1
4
0.651
0.011
7.59E−01
0.00E+00
0.00E+00

Cd27
1
4
0.632
0.087
6.50E−01
0.00E+00
0.00E+00

Sell
1
4
0.548
0.064
5.66E−01
0.00E+00
0.00E+00

Trbc2
1
6
0.962
0.084
1.76E+00
0.00E+00
0.00E+00

Ms4a4b
1
6
0.884
0.057
1.29E+00
0.00E+00
0.00E+00

Cd3g
1
6
0.907
0.024
1.28E+00
0.00E+00
0.00E+00

Igfbp4
1
6
0.632
0.014
1.24E+00
0.00E+00
0.00E+00

Cd3d
1
6
0.892
0.026
1.23E+00
0.00E+00
0.00E+00

Lef1
1
6
0.804
0.011
1.12E+00
0.00E+00
0.00E+00

Cd3e
1
6
0.846
0.02
1.12E+00
0.00E+00
0.00E+00

Trac
1
6
0.803
0.013
1.11E+00
0.00E+00
0.00E+00

Lat
1
6
0.755
0.098
8.34E−01
0.00E+00
0.00E+00

Lck
1
6
0.762
0.098
8.33E−01
0.00E+00
0.00E+00

Skap1
1
6
0.674
0.033
7.48E−01
0.00E+00
0.00E+00

Cd2
1
6
0.651
0.031
7.37E−01
0.00E+00
0.00E+00

Thy1
1
6
0.546
0.092
6.14E−01
0.00E+00
0.00E+00

Tcf7
1
6
0.531
0.058
5.47E−01
3.02E−285
5.35E−278

Trbc1
1
6
0.612
0.07
1.23E+00
1.52E−280
2.68E−273

Txk
1
6
0.509
0.076
5.15E−01
5.04E−207
8.93E−200

Igfbp4
1
7
0.632
0.058
1.15E+00
0.00E+00
0.00E+00

Igfbp4
1
8
0.632
0.013
1.23E+00
0.00E+00
0.00E+00

Cd3e
1
8
0.846
0.016
1.12E+00
0.00E+00
0.00E+00

Trac
1
8
0.803
0.056
1.06E+00
0.00E+00
0.00E+00

Ifi27l2a
1
8
0.578
0.054
8.03E−01
0.00E+00
0.00E+00

Rgs10
1
8
0.583
0.099
6.06E−01
0.00E+00
0.00E+00

Bcl2
1
9
0.744
0.095
1.20E+00
0.00E+00
0.00E+00

Igfbp4
1
9
0.632
0.066
1.19E+00
0.00E+00
0.00E+00

Lef1
1
9
0.804
0.057
1.07E+00
0.00E+00
0.00E+00

Trac
1
9
0.803
0.083
1.04E+00
0.00E+00
0.00E+00

Skap1
1
9
0.674
0.088
6.92E−01
0.00E+00
0.00E+00

Thy1
1
9
0.546
0.086
6.26E−01
4.2E−310
7.37E−303

Satb1
1
9
0.622
0.069
6.80E−01
1.35E−297
2.40E−290

Itgb7
1
9
0.545
0.075
5.40E−01
2.71E−259
4.80E−252

Tcf7
1
9
0.531
0.052
5.52E−01
6.98E−216
1.24E−208

Sell
1
9
0.548
0.062
5.69E−01
1.72E−207
3.05E−200

S100a10
1
9
0.545
0.093
4.84E−01
5.57E−181
9.87E−174

Ms4a4b
1
10
0.884
0.07
1.28E+00
0.00E+00
0.00E+00

Trbcl
1
10
0.612
0.064
1.26E+00
0.00E+00
0.00E+00

Bcl2
1
10
0.744
0.05
1.26E+00
0.00E+00
0.00E+00

Cd3g
1
10
0.907
0.055
1.25E+00
0.00E+00
0.00E+00

Igfbp4
1
10
0.632
0.037
1.23E+00
0.00E+00
0.00E+00

Cd3d
1
10
0.892
0.083
1.18E+00
0.00E+00
0.00E+00

Lef1
1
10
0.804
0.031
1.10E+00
0.00E+00
0.00E+00

Trac
1
10
0.803
0.05
1.08E+00
0.00E+00
0.00E+00

Cd3e
1
10
0.846
0.07
1.07E+00
0.00E+00
0.00E+00

Lat
1
10
0.755
0.076
8.77E−01
0.00E+00
0.00E+00

Ccnd2
1
10
0.669
0.044
8.10E−01
0.00E+00
0.00E+00

Ccr7
1
10
0.617
0.069
8.07E−01
0.00E+00
0.00E+00

Selplg
1
10
0.677
0.09
7.56E−01
0.00E+00
0.00E+00

Skap1
1
10
0.674
0.035
7.47E−01
0.00E+00
0.00E+00

Hcst
1
10
0.662
0.089
7.41E−01
0.00E+00
0.00E+00

Fyb
1
10
0.646
0.059
7.02E−01
0.00E+00
0.00E+00

Satb1
1
10
0.622
0.061
6.88E−01
0.00E+00
0.00E+00

Cd2
1
10
0.651
0.074
6.77E−01
0.00E+00
0.00E+00

Thy1
1
10
0.546
0.049
6.71E−01
0.00E+00
0.00E+00

Sell
1
10
0.548
0.042
5.90E−01
0.00E+00
0.00E+00

Tcf7
1
10
0.531
0.029
5.83E−01
0.00E+00
0.00E+00

Emp3
1
10
0.56
0.071
5.80E−01
0.00E+00
0.00E+00

Itgb7
1
10
0.545
0.058
5.68E−01
0.00E+00
0.00E+00

Txk
1
10
0.509
0.03
5.69E−01
2.54E−292
4.50E−285

Igfbp4
1
11
0.632
0.009
1.25E+00
0.00E+00
0.00E+00

Cd3d
1
11
0.892
0.047
1.21E+00
0.00E+00
0.00E+00

Cd3g
1
11
0.907
0.069
1.17E+00
0.00E+00
0.00E+00

Cd3e
1
11
0.846
0.021
1.11E+00
0.00E+00
0.00E+00

Lef1
1
11
0.804
0.058
1.07E+00
0.00E+00
0.00E+00

Ccr7
1
11
0.617
0.035
8.56E−01
0.00E+00
0.00E+00

Ifi27l2a
1
11
0.578
0.07
8.00E−01
7.21E−255
1.28E−247

Sell
1
11
0.548
0.094
5.24E−01
8.98E−225
1.59E−217

Ms4a4b
1
12
0.884
0.051
1.29E+00
0.00E+00
0.00E+00

Cd3d
1
12
0.892
0.028
1.23E+00
0.00E+00
0.00E+00

Igfbp4
1
12
0.632
0.03
1.20E+00
0.00E+00
0.00E+00

Trac
1
12
0.803
0.014
1.12E+00
0.00E+00
0.00E+00

Cd3e
1
12
0.846
0.057
1.07E+00
0.00E+00
0.00E+00

Lef1
1
12
0.804
0.073
1.06E+00
0.00E+00
0.00E+00

Ms4a6b
1
12
0.745
0.08
8.58E−01
0.00E+00
0.00E+00

Ccr7
1
12
0.617
0.047
8.25E−01
0.00E+00
0.00E+00

Cd2
1
12
0.651
0.026
7.43E−01
0.00E+00
0.00E+00

Ifi27l2a
1
12
0.578
0.05
8.36E−01
4.79E−257
8.48E−250

Sell
1
12
0.548
0.081
5.45E−01
3.43E−226
6.07E−219

Cd3d
1
14
0.892
0.061
1.16E+00
0.00E+00
0.00E+00

Igfbp4
1
14
0.632
0.066
1.13E+00
0.00E+00
0.00E+00

Cd3e
1
14
0.846
0.038
1.07E+00
0.00E+00
0.00E+00

Lat
1
14
0.755
0.053
8.72E−01
0.00E+00
0.00E+00

Trac
1
14
0.803
0.033
1.07E+00
3.82E−308
6.76E−301

Cd3g
1
14
0.907
0.058
1.19E+00
7.15E−303
1.27E−295

Skap1
1
14
0.674
0.072
6.92E−01
4.35E−271
7.69E−264

Cd2
1
14
0.651
0.058
6.94E−01
6.52E−249
1.16E−241

Thy1
1
14
0.546
0.085
6.21E−01
2.23E−247
3.95E−240

Cd3d
1
15
0.892
0.013
1.25E+00
5.73E−259
1.01E−251

Cd3g
1
15
0.907
0.04
1.26E+00
9.38E−259
1.66E−251

Ms4a4b
1
15
0.884
0.032
1.32E+00
4.71E−243
8.34E−236

Cd3e
1
15
0.846
0.025
1.12E+00
1.87E−198
3.31E−191

Trac
1
15
0.803
0.013
1.11E+00
1.47E−192
2.61E−185

Lef1
1
15
0.804
0.034
1.10E+00
3.09E−170
5.47E−163

Igfbp4
1
17
0.632
0.023
1.19E+00
1.92E−274
3.40E−267

Lef1
1
17
0.804
0.062
1.05E+00
3.70E−268
6.54E−261

Ccr7
1
17
0.617
0.062
8.27E−01
1.49E−178
2.63E−171

Cd2
1
17
0.651
0.082
6.70E−01
4.20E−168
7.43E−161

Igfbp4
1
20
0.632
0.042
1.20E+00
2.40E−263
4.25E−256

Cd3e
1
20
0.846
0.064
1.00E+00
5.78E−250
1.02E−242

Cd3d
1
20
0.892
0.093
1.09E+00
9.39E−239
1.66E−231

Cd3g
1
20
0.907
0.081
1.17E+00
7.45E−235
1.32E−227

Lef1
1
20
0.804
0.034
1.10E+00
1.92E−233
3.40E−226

Trac
1
20
0.803
0.064
1.05E+00
1.52E−211
2.68E−204

Skap1
1
20
0.674
0.047
7.29E−01
3.49E−167
6.17E−160

Igfbp4
1
21
0.632
0.073
1.13E+00
0.00E+00
0.00E+00

Cd3e
1
21
0.846
0.064
1.04E+00
1.92E−234
3.39E−227

Lat
1
21
0.755
0.098
8.26E−01
5.52E−234
9.77E−227

Lef1
1
21
0.804
0.038
1.05E+00
5.55E−206
9.82E−199

Cd3d
1
21
0.892
0.064
1.14E+00
4.12E−196
7.29E−189

Trac
1
21
0.803
0.034
1.06E+00
4.30E−184
7.61E−177

Skap1
1
21
0.674
0.073
6.97E−01
2.20E−169
3.89E−162

Cd3g
1
21
0.907
0.098
1.11E+00
8.39E−168
1.49E−160

Cd2
1
21
0.651
0.06
7.07E−01
1.01E−167
1.78E−160

Igfbp4
1
22
0.632
0.065
1.19E+00
2.64E−257
4.68E−250

Cd3d
1
22
0.892
0.022
1.24E+00
5.10E−251
9.02E−244

Cd3e
1
22
0.846
0.039
1.10E+00
1.11E−249
1.97E−242

Lef1
1
22
0.804
0.034
1.10E+00
8.02E−233
1.42E−225

Cd3g
1
22
0.907
0.039
1.27E+00
9.46E−231
1.68E−223

Lat
1
22
0.755
0.047
9.04E−01
3.23E−219
5.72E−212

Trac
1
22
0.803
0.013
1.12E+00
3.49E−218
6.17E−211

Lck
1
22
0.762
0.082
8.19E−01
4.80E−202
8.51E−195

Skap1
1
22
0.674
0.047
7.37E−01
3.47E−169
6.14E−162

Igfbp4
1
24
0.632
0.031
1.23E+00
4.23E−268
7.50E−261

Cd3e
1
24
0.846
0.004
1.14E+00
6.11E−261
1.08E−253

Cd3d
1
24
0.892
0.018
1.25E+00
5.34E−244
9.46E−237

Cd3g
1
24
0.907
0.027
1.22E+00
4.55E−231
8.06E−224

Trbc2
1
24
0.962
0.081
1.73E+00
8.05E−228
1.43E−220

Bcl2
1
24
0.744
0.094
1.11E+00
8.83E−227
1.56E−219

Ms4a4b
1
24
0.884
0.031
1.31E+00
1.08E−223
1.91E−216

Lat
1
24
0.755
0.027
9.28E−01
6.40E−222
1.13E−214

Lef1
1
24
0.804
0.04
1.07E+00
2.05E−221
3.63E−214

Trac
1
24
0.803
0.013
1.11E+00
4.43E−212
7.84E−205

Lck
1
24
0.762
0.058
8.80E−01
1.94E−209
3.43E−202

Gimap4
1
24
0.684
0.058
7.56E−01
1.39E−171
2.46E−164

Skap1
1
24
0.674
0.031
7.43E−01
5.48E−164
9.70E−157

Cd2
1
24
0.651
0.027
7.47E−01
4.77E−161
8.44E−154

Coro1a
1
25
0.969
0.1
1.56E+00
2.73E−307
4.83E−300

Trbc2
1
25
0.962
0.063
1.78E+00
3.50E−290
6.20E−283

Limd2
1
25
0.928
0.1
1.37E+00
3.75E−282
6.63E−275

Cd3d
1
25
0.892
0.018
1.25E+00
5.85E−242
1.04E−234

Cd3g
1
25
0.907
0.027
1.29E+00
3.89E−237
6.88E−230

Cd3e
1
25
0.846
0.009
1.13E+00
1.41E−226
2.49E−219

Ms4a4b
1
25
0.884
0.018
1.33E+00
1.38E−223
2.44E−216

Lef1
1
25
0.804
0.014
1.12E+00
2.08E−194
3.68E−187

Trac
1
25
0.803
0.009
1.12E+00
1.07E−189
1.89E−182

Lat
1
25
0.755
0.018
9.36E−01
1.97E−170
3.48E−163

Ptprcap
1
25
0.766
0.063
9.42E−01
2.29E−169
4.05E−162

Lck
1
25
0.762
0.045
8.80E−01
1.18E−166
2.08E−159

Cd3d
1
26
0.892
0.032
1.23E+00
1.65E−246
2.93E−239

Cd3e
1
26
0.846
0.078
1.04E+00
1.45E−240
2.56E−233

Cd3g
1
26
0.907
0.014
1.28E+00
7.36E−237
1.30E−229

Trbc2
1
26
0.962
0.083
1.73E+00
6.15E−236
1.09E−228

Igfbp4
1
26
0.632
0.083
1.04E+00
1.95E−234
3.46E−227

Ms4a4b
1
26
0.884
0.06
1.27E+00
1.53E−227
2.71E−220

Lef1
1
26
0.804
0.014
1.11E+00
2.28E−225
4.04E−218

Trac
1
26
0.803
0.005
1.12E+00
7.72E−214
1.37E−206

Lck
1
26
0.762
0.032
9.05E−01
9.29E−203
1.64E−195

Ms4a6b
1
26
0.745
0.028
8.94E−01
5.75E−166
1.02E−158

Trbc2
1
30
0.962
0.059
1.78E+00
8.60E−194
1.52E−186

Cd52
1
32
0.968
0.094
1.85E+00
1.35E−213
2.39E−206

Coro1a
1
32
0.969
0.085
1.59E+00
1.86E−190
3.29E−183

Trbc2
1
32
0.962
0.017
1.86E+00
8.07E−175
1.43E−167

Rac2
1
32
0.946
0.085
1.40E+00
2.49E−164
4.41E−157

Cd52
1
33
0.968
0.076
1.91E+00
5.65E−191
l.OOE−183

Igfbp4
1
34
0.632
0.03
1.24E+00
2.01E−242
3.56E−235

Cd3e
1
34
0.846
0.04
1.11E+00
4.59E−179
8.13E−172

Lat
1
34
0.755
0.06
8.96E−01
1.61E−176
2.85E−169

Cd3e
1
35
0.846
0.051
1.08E+00
3.66E−180
6.47E−173

Cd79a
2
3
0.995
0.025
2.38E+00
0.00E+00
0.00E+00

Iglc2
2
3
0.897
0.025
1.91E+00
0.00E+00
0.00E+00

Apoe
2
3
0.618
0.058
1.83E+00
0.00E+00
0.00E+00

H2-DMb2
2
3
0.966
0.032
1.80E+00
0.00E+00
0.00E+00

Ebf1
2
3
0.971
0.009
1.77E+00
0.00E+00
0.00E+00

Iglc3
2
3
0.886
0.023
1.56E+00
0.00E+00
0.00E+00

Iglc1
2
3
0.54
0.06
1.51E+00
0.00E+00
0.00E+00

Ms4a1
2
3
0.876
0.01
1.38E+00
0.00E+00
0.00E+00

Fcmr
2
3
0.817
0.006
1.37E+00
0.00E+00
0.00E+00

Mef2c
2
3
0.811
0.025
1.20E+00
0.00E+00
0.00E+00

Ifi30
2
3
0.787
0.087
1.18E+00
0.00E+00
0.00E+00

Ighd
2
3
0.738
0.005
1.17E+00
0.00E+00
0.00E+00

Mzb1
2
3
0.671
0.032
1.01E+00
0.00E+00
0.00E+00

Vpreb3
2
3
0.635
0.006
9.94E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
3
0.687
0.008
9.26E−01
0.00E+00
0.00E+00

Ccr7
2
3
0.544
0.03
8.89E−01
0.00E+00
0.00E+00

Fcer2a
2
3
0.613
0.004
8.78E−01
0.00E+00
0.00E+00

Hvcn1
2
3
0.712
0.089
8.71E−01
0.00E+00
0.00E+00

Cd24a
2
3
0.59
0.011
8.58E−01
0.00E+00
0.00E+00

Napsa
2
3
0.686
0.071
8.44E−01
0.00E+00
0.00E+00

Bank1
2
3
0.628
0.01
7.60E−01
0.00E+00
0.00E+00

Pou2f2
2
3
0.578
0.026
7.26E−01
0.00E+00
0.00E+00

Pkig
2
3
0.611
0.057
7.05E−01
0.00E+00
0.00E+00

Siglecg
2
3
0.569
0.01
6.85E−01
0.00E+00
0.00E+00

H2-Oa
2
3
0.545
0.027
6.66E−01
0.00E+00
0.00E+00

Fcrla
2
3
0.535
0.022
6.62E−01
0.00E+00
0.00E+00

Chchd10
2
3
0.549
0.09
6.54E−01
0.00E+00
0.00E+00

H2-Ob
2
3
0.542
0.006
6.30E−01
0.00E+00
0.00E+00

Snn
2
3
0.524
0.015
6.08E−01
0.00E+00
0.00E+00

Cd79a
2
4
0.995
0.027
2.36E+00
0.00E+00
0.00E+00

Iglc2
2
4
0.897
0.024
1.90E+00
0.00E+00
0.00E+00

Apoe
2
4
0.618
0.057
1.84E+00
0.00E+00
0.00E+00

H2-DMb2
2
4
0.966
0.07
1.70E+00
0.00E+00
0.00E+00

Ebf1
2
4
0.971
0.062
1.67E+00
0.00E+00
0.00E+00

Iglc3
2
4
0.886
0.029
1.55E+00
0.00E+00
0.00E+00

Iglc1
2
4
0.54
0.071
1.50E+00
0.00E+00
0.00E+00

Ms4a1
2
4
0.876
0.014
1.38E+00
0.00E+00
0.00E+00

Fcmr
2
4
0.817
0.007
1.37E+00
0.00E+00
0.00E+00

Ifi30
2
4
0.787
0.071
1.20E+00
0.00E+00
0.00E+00

Ighd
2
4
0.738
0.009
1.16E+00
0.00E+00
0.00E+00

Mzb1
2
4
0.671
0.033
1.00E+00
0.00E+00
0.00E+00

Vpreb3
2
4
0.635
0.005
9.93E−01
0.00E+00
0.00E+00

Dusp2
2
4
0.616
0.054
9.49E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
4
0.687
0.007
9.28E−01
0.00E+00
0.00E+00

Fcer2a
2
4
0.613
0.006
8.73E−01
0.00E+00
0.00E+00

Cd24a
2
4
0.59
0.014
8.54E−01
0.00E+00
0.00E+00

Ccr7
2
4
0.544
0.066
8.29E−01
0.00E+00
0.00E+00

Bank1
2
4
0.628
0.008
7.60E−01
0.00E+00
0.00E+00

Pou2f2
2
4
0.578
0.026
7.23E−01
0.00E+00
0.00E+00

Chchd10
2
4
0.549
0.061
6.85E−01
0.00E+00
0.00E+00

Fcrla
2
4
0.535
0.015
6.69E−01
0.00E+00
0.00E+00

Siglecg
2
4
0.569
0.038
6.43E−01
0.00E+00
0.00E+00

H2-Ob
2
4
0.542
0.011
6.26E−01
0.00E+00
0.00E+00

Snn
2
4
0.524
0.022
6.01E−01
0.00E+00
0.00E+00

Iglc2
2
5
0.897
0.071
1.86E+00
0.00E+00
0.00E+00

Apoe
2
5
0.618
0.085
1.78E+00
0.00E+00
0.00E+00

H2-DMb2
2
5
0.966
0.068
1.76E+00
0.00E+00
0.00E+00

Ebf1
2
5
0.971
0.032
1.75E+00
0.00E+00
0.00E+00

Iglc3
2
5
0.886
0.045
1.54E+00
0.00E+00
0.00E+00

Fcmr
2
5
0.817
0.034
1.34E+00
0.00E+00
0.00E+00

Ms4a1
2
5
0.876
0.05
1.34E+00
0.00E+00
0.00E+00

Ifi30
2
5
0.787
0.059
1.21E+00
0.00E+00
0.00E+00

Mef2c
2
5
0.811
0.014
1.21E+00
0.00E+00
0.00E+00

Cd83
2
5
0.735
0.037
1.19E+00
0.00E+00
0.00E+00

Ighd
2
5
0.738
0.015
1.16E+00
0.00E+00
0.00E+00

Mzb1
2
5
0.671
0.048
9.91E−01
0.00E+00
0.00E+00

Vpreb3
2
5
0.635
0.03
9.70E−01
0.00E+00
0.00E+00

Napsa
2
5
0.686
0.018
9.02E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
5
0.687
0.034
9.01E−01
0.00E+00
0.00E+00

Irf8
2
5
0.701
0.045
8.98E−01
0.00E+00
0.00E+00

Fcer2a
2
5
0.613
0.016
8.65E−01
0.00E+00
0.00E+00

Cd24a
2
5
0.59
0.043
8.26E−01
0.00E+00
0.00E+00

Capg
2
5
0.635
0.076
8.01E−01
0.00E+00
0.00E+00

Bank1
2
5
0.628
0.02
7.50E−01
0.00E+00
0.00E+00

Pkig
2
5
0.611
0.02
7.43E−01
0.00E+00
0.00E+00

Ctsh
2
5
0.61
0.028
7.37E−01
0.00E+00
0.00E+00

Unc93b1
2
5
0.593
0.029
6.96E−01
0.00E+00
0.00E+00

Siglecg
2
5
0.569
0.018
6.77E−01
0.00E+00
0.00E+00

Fcrla
2
5
0.535
0.016
6.69E−01
0.00E+00
0.00E+00

Snn
2
5
0.524
0.013
6.10E−01
0.00E+00
0.00E+00

H2-Ob
2
5
0.542
0.071
5.65E−01
0.00E+00
0.00E+00

Cd79a
2
6
0.995
0.056
2.29E+00
0.00E+00
0.00E+00

Ebf1
2
6
0.971
0.023
1.73E+00
0.00E+00
0.00E+00

Ms4a1
2
6
0.876
0.022
1.35E+00
0.00E+00
0.00E+00

Fcmr
2
6
0.817
0.019
1.35E+00
0.00E+00
0.00E+00

Vpreb3
2
6
0.635
0.01
9.81E−01
0.00E+00
0.00E+00

H2-Ob
2
6
0.542
0.031
6.01E−01
5.5E−312
9.68E−305

Ighd
2
6
0.738
0.058
1.11E+00
6.49E−296
1.15E−288

Fcer2a
2
6
0.613
0.014
8.65E−01
8.28E−282
1.47E−274

Dusp2
2
6
0.616
0.098
8.92E−01
3.32E−226
5.88E−219

Iglc2
2
7
0.897
0.084
1.84E+00
0.00E+00
0.00E+00

Ebf1
2
7
0.971
0.029
1.74E+00
0.00E+00
0.00E+00

H2-DMb2
2
7
0.966
0.091
1.73E+00
0.00E+00
0.00E+00

Iglc3
2
7
0.886
0.055
1.52E+00
0.00E+00
0.00E+00

Iglc1
2
7
0.54
0.096
1.47E+00
0.00E+00
0.00E+00

Fcmr
2
7
0.817
0.039
1.34E+00
0.00E+00
0.00E+00

Ms4a1
2
7
0.876
0.059
1.34E+00
0.00E+00
0.00E+00

Mef2c
2
7
0.811
0.019
1.21E+00
0.00E+00
0.00E+00

Ifi30
2
7
0.787
0.072
1.20E+00
0.00E+00
0.00E+00

Ighd
2
7
0.738
0.033
1.14E+00
0.00E+00
0.00E+00

Mzb1
2
7
0.671
0.056
9.76E−01
0.00E+00
0.00E+00

Vpreb3
2
7
0.635
0.037
9.61E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
7
0.687
0.031
9.03E−01
0.00E+00
0.00E+00

Napsa
2
7
0.686
0.019
9.01E−01
0.00E+00
0.00E+00

Fcer2a
2
7
0.613
0.018
8.60E−01
0.00E+00
0.00E+00

Irf8
2
7
0.701
0.07
8.56E−01
0.00E+00
0.00E+00

Cd24a
2
7
0.59
0.063
7.87E−01
0.00E+00
0.00E+00

Cd72
2
7
0.628
0.067
7.60E−01
0.00E+00
0.00E+00

Bank1
2
7
0.628
0.023
7.46E−01
0.00E+00
0.00E+00

Ctsh
2
7
0.61
0.03
7.35E−01
0.00E+00
0.00E+00

Pkig
2
7
0.611
0.041
7.21E−01
0.00E+00
0.00E+00

Siglecg
2
7
0.569
0.012
6.82E−01
0.00E+00
0.00E+00

Fcrla
2
7
0.535
0.02
6.63E−01
0.00E+00
0.00E+00

Unc93b1
2
7
0.593
0.065
6.58E−01
0.00E+00
0.00E+00

H2-Oa
2
7
0.545
0.094
5.88E−01
0.00E+00
0.00E+00

Snn
2
7
0.524
0.043
5.79E−01
0.00E+00
0.00E+00

H2-Ob
2
7
0.542
0.089
5.44E−01
0.00E+00
0.00E+00

Cd79a
2
8
0.995
0.022
2.36E+00
0.00E+00
0.00E+00

Iglc2
2
8
0.897
0.029
1.91E+00
0.00E+00
0.00E+00

Apoe
2
8
0.618
0.058
1.84E+00
0.00E+00
0.00E+00

H2-DMb2
2
8
0.966
0.029
1.79E+00
0.00E+00
0.00E+00

Cd79b
2
8
0.952
0.025
1.78E+00
0.00E+00
0.00E+00

Ebf1
2
8
0.971
0.016
1.76E+00
0.00E+00
0.00E+00

Iglc1
2
8
0.54
0.071
1.49E+00
0.00E+00
0.00E+00

Iglc3
2
8
0.886
0.04
1.47E+00
0.00E+00
0.00E+00

Ms4a1
2
8
0.876
0.008
1.38E+00
0.00E+00
0.00E+00

Fcmr
2
8
0.817
0.009
1.37E+00
0.00E+00
0.00E+00

Ifi30
2
8
0.787
0.058
1.21E+00
0.00E+00
0.00E+00

Ighd
2
8
0.738
0.016
1.15E+00
0.00E+00
0.00E+00

Mzb1
2
8
0.671
0.025
1.01E+00
0.00E+00
0.00E+00

Vpreb3
2
8
0.635
0.007
9.89E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
8
0.687
0.018
9.15E−01
0.00E+00
0.00E+00

Fcer2a
2
8
0.613
0.004
8.75E−01
0.00E+00
0.00E+00

Cd24a
2
8
0.59
0.013
8.54E−01
0.00E+00
0.00E+00

Capg
2
8
0.635
0.089
7.74E−01
0.00E+00
0.00E+00

Bank1
2
8
0.628
0.01
7.60E−01
0.00E+00
0.00E+00

Pou2f2
2
8
0.578
0.049
6.98E−01
0.00E+00
0.00E+00

Siglecg
2
8
0.569
0.013
6.81E−01
0.00E+00
0.00E+00

Chchd10
2
8
0.549
0.07
6.79E−01
0.00E+00
0.00E+00

Ctsh
2
8
0.61
0.087
6.76E−01
0.00E+00
0.00E+00

Fcrla
2
8
0.535
0.015
6.69E−01
0.00E+00
0.00E+00

H2-Ob
2
8
0.542
0.01
6.27E−01
0.00E+00
0.00E+00

H2-Oa
2
8
0.545
0.062
6.24E−01
0.00E+00
0.00E+00

Snn
2
8
0.524
0.013
6.09E−01
0.00E+00
0.00E+00

S100a10
2
9
0.557
0.093
6.13E−01
5.99E−251
1.06E−243

Ighd
2
9
0.738
0.067
1.08E+00
6.91E−174
1.22E−166

Ighd
2
10
0.738
0.046
1.09E+00
0.00E+00
0.00E+00

S100a10
2
10
0.557
0.053
6.71E−01
0.00E+00
0.00E+00

S100a11
2
10
0.534
0.09
5.49E−01
0.00E+00
0.00E+00

Ccr7
2
10
0.544
0.069
8.35E−01
4.09E−304
7.25E−297

Cd79a
2
11
0.995
0.019
2.38E+00
0.00E+00
0.00E+00

Iglc2
2
11
0.897
0.027
1.91E+00
0.00E+00
0.00E+00

H2-DMb2
2
11
0.966
0.036
1.79E+00
0.00E+00
0.00E+00

Ebf1
2
11
0.971
0.004
1.78E+00
0.00E+00
0.00E+00

Cd79b
2
11
0.952
0.048
1.76E+00
0.00E+00
0.00E+00

Iglc3
2
11
0.886
0.024
1.56E+00
0.00E+00
0.00E+00

Ms4a1
2
11
0.876
0.007
1.39E+00
0.00E+00
0.00E+00

Fcmr
2
11
0.817
0.004
1.38E+00
0.00E+00
0.00E+00

Ifi30
2
11
0.787
0.064
1.21E+00
0.00E+00
0.00E+00

Mef2c
2
11
0.811
0.048
1.17E+00
0.00E+00
0.00E+00

Ighd
2
11
0.738
0.008
1.16E+00
0.00E+00
0.00E+00

Mzb1
2
11
0.671
0.029
1.01E+00
0.00E+00
0.00E+00

Vpreb3
2
11
0.635
0.012
9.88E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
11
0.687
0.016
9.17E−01
0.00E+00
0.00E+00

Bank1
2
11
0.628
0.001
7.69E−01
0.00E+00
0.00E+00

Fcer2a
2
11
0.613
0.004
8.77E−01
4.1E−315
7.22E−308

Pkig
2
11
0.611
0.055
7.09E−01
1.75E−306
3.09E−299

Apoe
2
11
0.618
0.037
1.86E+00
1.07E−298
1.90E−291

Siglecg
2
11
0.569
0.01
6.85E−01
5.52E−298
9.77E−291

Ctsh
2
11
0.61
0.07
6.93E−01
1.24E−285
2.19E−278

H2-Ob
2
11
0.542
0.007
6.30E−01
1.78E−281
3.16E−274

Snn
2
11
0.524
0.007
6.17E−01
4.96E−272
8.78E−265

Fcrla
2
11
0.535
0.017
6.67E−01
2.76E−271
4.89E−264

Iglc1
2
11
0.54
0.05
1.52E+00
3.25E−257
5.76E−250

H2-Oa
2
11
0.545
0.039
6.53E−01
9.48E−246
1.68E−238

Ccr7
2
11
0.544
0.035
8.84E−01
2.87E−242
5.09E−235

Chchd10
2
11
0.549
0.058
6.90E−01
1.12E−236
1.99E−229

Pou2f2
2
11
0.578
0.092
6.49E−01
1.25E−223
2.21E−216

Cd79a
2
12
0.995
0.036
2.36E+00
0.00E+00
0.00E+00

Iglc2
2
12
0.897
0.037
1.90E+00
0.00E+00
0.00E+00

H2-DMb2
2
12
0.966
0.043
1.78E+00
0.00E+00
0.00E+00

Ebf1
2
12
0.971
0.009
1.77E+00
0.00E+00
0.00E+00

Iglc3
2
12
0.886
0.019
1.56E+00
0.00E+00
0.00E+00

Ms4a1
2
12
0.876
0.02
1.37E+00
0.00E+00
0.00E+00

Fcmr
2
12
0.817
0.012
1.37E+00
0.00E+00
0.00E+00

Mef2c
2
12
0.811
0.021
1.20E+00
0.00E+00
0.00E+00

Ifi30
2
12
0.787
0.069
1.20E+00
0.00E+00
0.00E+00

Ighd
2
12
0.738
0.005
1.17E+00
0.00E+00
0.00E+00

Mzb1
2
12
0.671
0.034
1.00E+00
0.00E+00
0.00E+00

Vpreb3
2
12
0.635
0.003
9.96E−01
0.00E+00
0.00E+00

Tnfrsf13c
2
12
0.687
0.009
9.26E−01
0.00E+00
0.00E+00

Napsa
2
12
0.686
0.068
8.50E−01
0.00E+00
0.00E+00

Bank1
2
12
0.628
0.003
7.67E−01
0.00E+00
6.42E−302

Pkig
2
12
0.611
0.064
6.98E−01
7.21E−288
1.28E−280

Fcer2a
2
12
0.613
0.008
8.74E−01
8.49E−284
1.50E−276

Ly6e
2
12
0.673
0.088
1.03E+00
2.85E−281
5.05E−274

Siglecg
2
12
0.569
0.012
6.83E−01
2.14E−275
3.79E−268

Apoe
2
12
0.618
0.053
1.84E+00
1.70E−267
3.01E−260

Fcrla
2
12
0.535
0.012
6.72E−01
4.54E−263
8.05E−256

H2-Ob
2
12
0.542
0.01
6.27E−01
5.35E−258
9.48E−251

Ctsh
2
12
0.61
0.098
6.63E−01
3.85E−247
6.81E−240

Snn
2
12
0.524
0.012
6.11E−01
3.77E−245
6.68E−238

Ctss
2
12
0.601
0.087
6.12E−01
8.84E−239
1.57E−231

Cd24a
2
12
0.59
0.069
7.66E−01
2.56E−238
4.53E−231

Iglc1
2
12
0.54
0.07
1.50E+00
5.13E−224
9.09E−217

Chchd10
2
12
0.549
0.067
6.81E−01
8.46E−217
1.50E−209

Ccr7
2
12
0.544
0.047
8.53E−01
7.54E−211
1.33E−203

Ighd
2
13
0.738
0.006
1.17E+00
9.31E−288
1.65E−280

H2-Aa
2
13
0.994
0.076
3.19E+00
1.58E−267
2.80E−260

Mef2c
2
13
0.811
0.009
1.22E+00
8.09E−185
1.43E−177

H2-Eb1
2
13
0.989
0.059
2.65E+00
2.70E−178
4.77E−171

Fcmr
2
13
0.817
0.014
1.37E+00
3.39E−176
6.01E−169

Fcer2a
2
13
0.613
0.007
8.74E−01
1.56E−175
2.75E−168

Ebf1
2
13
0.971
0.004
1.78E+00
4.68E−172
8.29E−165

Bank1
2
13
0.628
0.004
7.66E−01
7.24E−166
1.28E−158

Cd79a
2
14
0.995
0.081
2.25E+00
0.00E+00
0.00E+00

Ebf1
2
14
0.971
0.034
1.71E+00
2.31E−299
4.09E−292

Ms4a1
2
14
0.876
0.053
1.31E+00
1.80E−295
3.19E−288

Iglc2
2
14
0.897
0.063
1.79E+00
5.45E−295
9.65E−288

Mzb1
2
14
0.671
0.094
8.58E−01
1.05E−239
1.86E−232

Fcmr
2
14
0.817
0.023
1.34E+00
2.25E−231
3.98E−224

Tnfrsf13c
2
14
0.687
0.091
8.31E−01
1.51E−209
2.67E−202

Vpreb3
2
14
0.635
0.014
9.81E−01
1.89E−184
3.34E−177

Chchd10
2
14
0.549
0.085
6.44E−01
4.45E−175
7.87E−168

Fcrla
2
14
0.535
0.061
6.16E−01
3.76E−165
6.66E−158

Cd79a
2
15
0.995
0.021
2.38E+00
0.00E+00
0.00E+00

Ighm
2
15
0.923
0.07
2.19E+00
9.9E−315
1.75E−307

Ebf1
2
15
0.971
0.013
1.76E+00
9.9E−310
1.77E−302

H2-DMb2
2
15
0.966
0.027
1.80E+00
2.09E−279
3.70E−272

Ighd
2
15
0.738
0
1.17E+00
7.89E−252
1.40E−244

Cd79b
2
15
0.952
0.061
1.74E+00
4.07E−241
7.21E−234

Iglc2
2
15
0.897
0.019
1.92E+00
5.23E−228
9.27E−221

Ms4a1
2
15
0.876
0
1.39E+00
7.94E−214
1.41E−206

Fcmr
2
15
0.817
0.008
1.37E+00
9.13E−206
1.62E−198

Iglc3
2
15
0.886
0.006
1.58E+00
4.90E−205
8.68E−198

Mef2c
2
15
0.811
0.038
1.19E+00
1.72E−183
3.05E−176

Ighm
2
16
0.923
0.049
2.20E+00
3.66E−252
6.49E−245

Cd79a
2
16
0.995
0.028
2.37E+00
2.35E−217
4.16E−210

Ighd
2
16
0.738
0.008
1.16E+00
1.14E−200
2.02E−193

Ebf1
2
16
0.971
0.036
1.73E+00
4.09E−185
7.24E−178

H2-DMb2
2
16
0.966
0.015
1.81E+00
1.88E−177
3.32E−170

Cd79a
2
17
0.995
0.082
2.30E+00
0.00E+00
0.00E+00

H2-DMb2
2
17
0.966
0.059
1.76E+00
0.00E+00
0.00E+00

Ebf1
2
17
0.971
0.018
1.75E+00
0.00E+00
0.00E+00

Iglc3
2
17
0.886
0.035
1.54E+00
7.17E−291
1.27E−283

Ms4a1
2
17
0.876
0.035
1.36E+00
5.25E−281
9.30E−274

Iglc2
2
17
0.897
0.05
1.88E+00
4.90E−280
8.68E−273

Fcmr
2
17
0.817
0.021
1.36E+00
1.61E−219
2.85E−212

Mef2c
2
17
0.811
0.041
1.17E+00
3.32E−204
5.88E−197

Cd83
2
17
0.735
0.065
1.16E+00
1.16E−168
2.06E−161

Tnfrsf13c
2
17
0.687
0.038
8.98E−01
1.02E−163
1.80E−156

Ebf1
2
18
0.971
0.036
1.74E+00
0.00E+00
0.00E+00

Iglc3
2
18
0.886
0.053
1.53E+00
1.07E−244
1.89E−237

Iglc2
2
18
0.897
0.085
1.85E+00
2.09E−227
3.71E−220

Ms4a1
2
18
0.876
0.078
1.31E+00
6.40E−223
1.13E−215

Mef2c
2
18
0.811
0.021
1.21E+00
1.58E−182
2.79E−175

Fcmr
2
18
0.817
0.039
1.34E+00
2.44E−182
4.32E−175

Ifi30
2
18
0.787
0.078
1.19E+00
1.51E−169
2.68E−162

Cd79a
2
19
0.995
0.072
2.33E+00
0.00E+00
0.00E+00

Ebf1
2
19
0.971
0.016
1.76E+00
8.53E−302
1.51E−294

H2-DMb2
2
19
0.966
0.04
1.78E+00
1.62E−288
2.88E−281

Cd79b
2
19
0.952
0.064
1.74E+00
1.02E−252
1.81E−245

Iglc3
2
19
0.886
0.02
1.56E+00
2.01E−206
3.55E−199

Iglc2
2
19
0.897
0.036
1.90E+00
7.14E−204
1.26E−196

Ms4a1
2
19
0.876
0.028
1.37E+00
8.31E−192
1.47E−184

Fcmr
2
19
0.817
0.012
1.37E+00
1.78E−162
3.16E−155

Cd79a
2
21
0.995
0.098
2.28E+00
3.60E−235
6.37E−228

Iglc3
2
21
0.886
0.081
1.49E+00
3.39E−181
5.99E−174

Ms4a1
2
21
0.876
0.034
1.36E+00
3.37E−174
5.96E−167

Cd79a
2
22
0.995
0.06
2.27E+00
1.90E−282
3.36E−275

Ebf1
2
22
0.971
0.043
1.70E+00
9.75E−224
1.73E−216

Iglc3
2
22
0.886
0.069
1.49E+00
1.76E−207
3.11E−200

Ms4a1
2
22
0.876
0.039
1.34E+00
3.73E−194
6.61E−187

Iglc2
2
22
0.897
0.056
1.80E+00
5.88E−186
1.04E−178

Cd79a
2
24
0.995
0.049
2.35E+00
1.67E−304
2.95E−297

Iglc3
2
24
0.886
0.081
1.45E+00
9.13E−201
1.62E−193

Ms4a1
2
24
0.876
0.045
1.35E+00
7.25E−194
1.28E−186

Iglc2
2
24
0.897
0.04
1.89E+00
2.69E−190
4.77E−183

Cd79a
2
25
0.995
0.027
2.38E+00
0.00E+00
0.00E+00

H2-DMb2
2
25
0.966
0.045
1.78E+00
8.70E−269
1.54E−261

Cd79b
2
25
0.952
0.009
1.80E+00
8.96E−260
1.59E−252

Coro1a
2
25
0.958
0.1
1.62E+00
1.35E−250
2.40E−243

Cd37
2
25
0.902
0.014
1.40E+00
1.55E−210
2.74E−203

Ptprcap
2
25
0.902
0.063
1.31E+00
5.36E−209
9.49E−202

Ms4a1
2
25
0.876
0
1.39E+00
4.12E−203
7.29E−196

Ighm
2
25
0.923
0.077
2.18E+00
2.75E−199
4.86E−192

Iglc3
2
25
0.886
0.027
1.55E+00
1.18E−195
2.08E−188

Iglc2
2
25
0.897
0.036
1.90E+00
2.77E−191
4.90E−184

Fcmr
2
25
0.817
0
1.38E+00
5.24E−159
9.27E−152

Cd79a
2
26
0.995
0.018
2.38E+00
5.72E−297
1.01E−289

H2-DMb2
2
26
0.966
0.069
1.73E+00
5.83E−248
1.03E−240

Ebf1
2
26
0.971
0.005
1.78E+00
3.67E−244
6.50E−237

Cd79b
2
26
0.952
0.092
1.70E+00
1.03E−224
1.83E−217

Iglc3
2
26
0.886
0.069
1.47E+00
1.20E−205
2.13E−198

Ms4a1
2
26
0.876
0.014
1.38E+00
1.91E−200
3.38E−193

Iglc2
2
26
0.897
0.055
1.86E+00
3.31E−189
5.87E−182

Cd79a
2
30
0.995
0.052
2.32E+00
5.67E−240
l.OOE−232

H2-DMb2
2
30
0.966
0.03
1.79E+00
3.43E−182
6.07E−175

Ebf1
2
30
0.971
0.022
1.76E+00
4.17E−181
7.38E−174

Cd79b
2
30
0.952
0.059
1.71E+00
2.66E−160
4.71E−153

Cd79a
2
31
0.995
0.037
2.37E+00
2.47E−182
4.38E−175

Cd52
2
32
0.991
0.094
2.51E+00
1.96E−209
3.48E−202

Cd79a
2
32
0.995
0.009
2.39E+00
1.10E−204
1.95E−197

Cd52
2
33
0.991
0.076
2.57E+00
3.71E−173
6.56E−166

Cd79a
2
33
0.995
0.057
2.34E+00
2.24E−169
3.96E−162

Ncr1
3
4
0.709
0.093
9.33E−01
0.00E+00
0.00E+00

Tmem176b
3
5
0.975
0.016
1.86E+00
0.00E+00
0.00E+00

Lgals3
3
5
0.938
0.012
1.72E+00
0.00E+00
0.00E+00

Tmem176a
3
5
0.952
0.018
1.69E+00
0.00E+00
0.00E+00

Car2
3
5
0.915
0.041
1.57E+00
0.00E+00
0.00E+00

Fcer1g
3
5
0.904
0.02
1.53E+00
0.00E+00
0.00E+00

Lmo4
3
5
0.86
0.101
1.35E+00
0.00E+00
0.00E+00

Gadd45b
3
5
0.621
0.051
1.32E+00
0.00E+00
0.00E+00

Serpinb1a
3
5
0.777
0.01
1.31E+00
0.00E+00
0.00E+00

Gem
3
5
0.587
0.028
1.21E+00
0.00E+00
0.00E+00

Nr4a1
3
5
0.684
0.095
1.14E+00
0.00E+00
0.00E+00

Klrk1
3
5
0.742
0.013
1.12E+00
0.00E+00
0.00E+00

Ckb
3
5
0.802
0.022
1.10E+00
0.00E+00
0.00E+00

Ncr1
3
5
0.709
0.002
1.05E+00
0.00E+00
0.00E+00

Bhlhe40
3
5
0.688
0.015
1.04E+00
0.00E+00
0.00E+00

Upp1
3
5
0.722
0.001
1.04E+00
0.00E+00
0.00E+00

Rora
3
5
0.756
0.016
1.03E+00
0.00E+00
0.00E+00

Ffar2
3
5
0.693
0.002
9.97E−01
0.00E+00
0.00E+00

Ncoa7
3
5
0.687
0.048
9.89E−01
0.00E+00
0.00E+00

Tcrg-C1
3
5
0.637
0.012
9.84E−01
0.00E+00
0.00E+00

Serpina3g
3
5
0.578
0.005
9.43E−01
0.00E+00
0.00E+00

Ikzf2
3
5
0.705
0.046
9.32E−01
0.00E+00
0.00E+00

St6galnac3
3
5
0.633
0.022
7.02E−01
0.00E+00
0.00E+00

Prr29
3
5
0.51
0.002
6.80E−01
0.00E+00
0.00E+00

Chad
3
5
0.55
0.003
6.78E−01
0.00E+00
0.00E+00

Stk19
3
5
0.567
0.035
6.78E−01
0.00E+00
0.00E+00

Podnl1
3
5
0.625
0.042
6.72E−01
0.00E+00
0.00E+00

Nrgn
3
5
0.509
0.004
6.68E−01
0.00E+00
0.00E+00

Asb2
3
5
0.507
0.006
6.62E−01
0.00E+00
0.00E+00

Maf
3
5
0.527
0.008
6.40E−01
0.00E+00
0.00E+00

Maff
3
5
0.508
0.023
7.09E−01
2.12E−304
3.75E−297

Tnfrsf25
3
5
0.527
0.034
5.52E−01
1.58E−289
2.79E−282

Cd160
3
5
0.503
0.039
5.57E−01
2.92E−248
5.17E−241

Samsn1
3
5
0.531
0.06
6.13E−01
9.53E−242
1.69E−234

Nfkbiz
3
5
0.511
0.074
6.23E−01
1.15E−204
2.03E−197

Capg
3
5
0.536
0.076
6.29E−01
2.48E−204
4.39E−197

Cxcr6
3
6
0.935
0.078
1.57E+00
0.00E+00
0.00E+00

Id2
3
6
0.824
0.096
1.50E+00
0.00E+00
0.00E+00

Car2
3
6
0.915
0.101
1.50E+00
0.00E+00
0.00E+00

Trbc2
3
6
0.818
0.084
1.33E+00
0.00E+00
0.00E+00

Serpinb1a
3
6
0.777
0.062
1.26E+00
0.00E+00
0.00E+00

Trbc1
3
6
0.862
0.07
1.24E+00
0.00E+00
0.00E+00

Upp1
3
6
0.722
0.044
9.97E−01
0.00E+00
0.00E+00

Ncr1
3
6
0.709
0.067
9.84E−01
0.00E+00
0.00E+00

Ffar2
3
6
0.693
0.035
9.63E−01
0.00E+00
0.00E+00

Tcrg-C1
3
6
0.637
0.037
9.61E−01
0.00E+00
0.00E+00

Rora
3
6
0.756
0.09
9.48E−01
0.00E+00
0.00E+00

Txk
3
6
0.747
0.076
8.89E−01
0.00E+00
0.00E+00

Prr29
3
6
0.51
0.02
6.62E−01
5.50E−298
9.75E−291

Gimap7
3
6
0.556
0.043
6.16E−01
6.91E−293
1.22E−285

Cd160
3
6
0.503
0.021
5.76E−01
9.52E−293
1.69E−285

Serpina3g
3
6
0.578
0.064
8.84E−01
4.05E−282
7.17E−275

Maf
3
6
0.527
0.015
6.33E−01
1.63E−281
2.89E−274

Lck
3
6
0.584
0.098
5.60E−01
5.02E−279
8.89E−272

Nrgn
3
6
0.509
0.04
6.29E−01
6.28E−276
1.11E−268

Tnfrsf25
3
6
0.527
0.027
5.58E−01
6.33E−269
1.12E−261

Ptpn22
3
6
0.552
0.057
5.86E−01
1.22E−268
2.16E−261

Asb2
3
6
0.507
0.05
6.16E−01
3.58E−264
6.35E−257

Skap1
3
6
0.5
0.033
5.10E−01
6.03E−260
1.07E−252

Il18r1
3
6
0.592
0.048
6.50E−01
2.01E−252
3.56E−245

Gimap5
3
6
0.5
0.058
5.21E−01
2.77E−245
4.90E−238

Chad
3
6
0.55
0.051
6.24E−01
1.34E−231
2.37E−224

Maff
3
6
0.508
0.072
6.55E−01
2.85E−204
5.05E−197

Tmem176b
3
7
0.975
0.031
1.83E+00
0.00E+00
0.00E+00

Lgals3
3
7
0.938
0.03
1.68E+00
0.00E+00
0.00E+00

Tmem176a
3
7
0.952
0.021
1.68E+00
0.00E+00
0.00E+00

Car2
3
7
0.915
0.019
1.58E+00
0.00E+00
0.00E+00

Fcer1g
3
7
0.904
0.019
1.53E+00
0.00E+00
0.00E+00

Cxcr6
3
7
0.935
0.099
1.50E+00
0.00E+00
0.00E+00

Serpinb1a
3
7
0.777
0.022
1.30E+00
0.00E+00
0.00E+00

Gem
3
7
0.587
0.088
1.12E+00
0.00E+00
0.00E+00

Klrk1
3
7
0.742
0.009
1.12E+00
0.00E+00
0.00E+00

Ncr1
3
7
0.709
0.006
1.05E+00
0.00E+00
0.00E+00

Upp1
3
7
0.722
0.004
1.04E+00
0.00E+00
0.00E+00

Ffar2
3
7
0.693
0.014
9.79E−01
0.00E+00
0.00E+00

Tcrg-C1
3
7
0.637
0.014
9.79E−01
0.00E+00
0.00E+00

Serpina3g
3
7
0.578
0.045
8.73E−01
0.00E+00
0.00E+00

Prr29
3
7
0.51
0.001
6.80E−01
0.00E+00
0.00E+00

Chad
3
7
0.55
0.005
6.75E−01
0.00E+00
0.00E+00

Il18r1
3
7
0.592
0.034
6.64E−01
0.00E+00
0.00E+00

Stk19
3
7
0.567
0.066
6.47E−01
0.00E+00
0.00E+00

Nrgn
3
7
0.509
0.042
5.78E−01
0.00E+00
0.00E+00

Cd160
3
7
0.503
0.08
4.93E−01
4.88E−261
8.64E−254

Runx3
3
7
0.518
0.101
4.63E−01
9.65E−246
1.71E−238

Cxcr6
3
8
0.935
0.085
1.56E+00
0.00E+00
0.00E+00

Serpinb1a
3
8
0.777
0.052
1.24E+00
0.00E+00
0.00E+00

Upp1
3
8
0.722
0.026
1.02E+00
0.00E+00
0.00E+00

Ffar2
3
8
0.693
0.021
9.74E−01
0.00E+00
0.00E+00

Ncoa7
3
8
0.687
0.08
9.54E−01
0.00E+00
0.00E+00

Tcrg-C1
3
8
0.637
0.036
9.43E−01
0.00E+00
0.00E+00

Prr29
3
8
0.51
0.008
6.74E−01
0.00E+00
0.00E+00

Chad
3
8
0.55
0.042
6.37E−01
0.00E+00
0.00E+00

Tnfrsf25
3
8
0.527
0.048
5.34E−01
1.65E−292
2.92E−285

Stk19
3
8
0.567
0.08
6.28E−01
6.16E−288
1.09E−280

Maf
3
8
0.527
0.079
5.54E−01
1.24E−241
2.20E−234

Capg
3
8
0.536
0.089
6.01E−01
5.04E−241
8.92E−234

Asb2
3
8
0.507
0.088
5.67E−01
3.60E−224
6.37E−217

Tmem176b
3
9
0.975
0.039
1.83E+00
0.00E+00
0.00E+00

Lgals3
3
9
0.938
0.035
1.68E+00
0.00E+00
0.00E+00

Tmem176a
3
9
0.952
0.034
1.67E+00
0.00E+00
0.00E+00

Cxcr6
3
9
0.935
0.017
1.64E+00
0.00E+00
0.00E+00

Fcer1g
3
9
0.904
0.038
1.51E+00
0.00E+00
0.00E+00

Il7r
3
9
0.911
0.043
1.48E+00
0.00E+00
0.00E+00

S100a10
3
9
0.914
0.093
1.29E+00
0.00E+00
0.00E+00

Ckb
3
9
0.802
0.052
1.05E+00
0.00E+00
0.00E+00

Serpinb1a
3
9
0.777
0.067
1.22E+00
1.71E−278
3.03E−271

Ctsw
3
9
0.705
0.04
8.99E−01
9.95E−276
1.76E−268

Ncr1
3
9
0.709
0.008
1.05E+00
2.71E−258
4.80E−251

Txk
3
9
0.747
0.055
9.10E−01
1.58E−257
2.79E−250

Upp1
3
9
0.722
0.015
1.03E+00
3.55E−250
6.29E−243

Cd7
3
9
0.733
0.077
1.31E+00
1.84E−249
3.27E−242

Rora
3
9
0.756
0.013
1.04E+00
1.38E−247
2.45E−240

Tcrg-C1
3
9
0.637
0.013
9.88E−01
8.95E−242
1.58E−234

Klrk1
3
9
0.742
0.005
1.13E+00
1.02E−238
1.81E−231

Ffar2
3
9
0.693
0.014
9.81E−01
3.26E−234
5.77E−227

Bcl2
3
9
0.602
0.095
8.37E−01
1.69E−220
2.99E−213

Sla
3
9
0.629
0.063
8.19E−01
3.88E−220
6.88E−213

Bhlhe40
3
9
0.688
0.05
9.97E−01
7.34E−214
1.30E−206

Il2rb
3
9
0.514
0.041
5.57E−01
3.47E−213
6.14E−206

Gpr183
3
9
0.635
0.07
7.46E−01
2.56E−212
4.53E−205

Podnl1
3
9
0.625
0.016
7.00E−01
1.20E−211
2.13E−204

Ikzf2
3
9
0.705
0.015
9.81E−01
9.17E−205
1.62E−197

Prr29
3
9
0.51
0.008
6.73E−01
1.19E−202
2.11E−195

Cd160
3
9
0.503
0.006
5.92E−01
2.80E−193
4.96E−186

Serpina3g
3
9
0.578
0.021
9.25E−01
3.16E−191
5.60E−184

Nabp1
3
9
0.569
0.082
7.92E−01
1.76E−189
3.11E−182

Ptpn22
3
9
0.552
0.038
6.06E−01
1.34E−186
2.37E−179

Tnfrsf25
3
9
0.527
0.012
5.74E−01
7.36E−183
1.30E−175

St6galnac3
3
9
0.633
0.019
7.05E−01
8.09E−183
1.43E−175

Asb2
3
9
0.507
0.025
6.37E−01
9.64E−182
1.71E−174

Il18r1
3
9
0.592
0.009
6.95E−01
1.07E−168
1.89E−161

Maf
3
9
0.527
0.016
6.27E−01
4.18E−166
7.39E−159

Runx3
3
9
0.518
0.097
4.50E−01
3.68E−162
6.51E−155

Maff
3
9
0.508
0.015
7.17E−01
5.96E−161
1.05E−153

Tmem176b
3
10
0.975
0.025
1.83E+00
0.00E+00
0.00E+00

Lgals3
3
10
0.938
0.03
1.70E+00
0.00E+00
0.00E+00

Tmem176a
3
10
0.952
0.023
1.67E+00
0.00E+00
0.00E+00

Cxcr6
3
10
0.935
0.013
1.64E+00
0.00E+00
0.00E+00

Id2
3
10
0.824
0.051
1.56E+00
0.00E+00
0.00E+00

Fcer1g
3
10
0.904
0.032
1.51E+00
0.00E+00
0.00E+00

Car2
3
10
0.915
0.1
1.50E+00
0.00E+00
0.00E+00

Il7r
3
10
0.911
0.026
1.49E+00
0.00E+00
0.00E+00

Emb
3
10
0.914
0.057
1.37E+00
0.00E+00
0.00E+00

Sepp1
3
10
0.904
0.075
1.36E+00
0.00E+00
0.00E+00

S100a10
3
10
0.914
0.053
1.35E+00
0.00E+00
0.00E+00

Cd7
3
10
0.733
0.043
1.34E+00
0.00E+00
0.00E+00

Selplg
3
10
0.901
0.09
1.28E+00
0.00E+00
0.00E+00

Trbc1
3
10
0.862
0.064
1.27E+00
0.00E+00
0.00E+00

Hcst
3
10
0.872
0.089
1.27E+00
0.00E+00
0.00E+00

Serpinb1a
3
10
0.777
0.088
1.18E+00
0.00E+00
0.00E+00

Klrk1
3
10
0.742
0.005
1.13E+00
0.00E+00
0.00E+00

Nr4a1
3
10
0.684
0.093
1.12E+00
0.00E+00
0.00E+00

Ckb
3
10
0.802
0.027
1.09E+00
0.00E+00
0.00E+00

Ncr1
3
10
0.709
0.009
1.05E+00
0.00E+00
0.00E+00

Rora
3
10
0.756
0.008
1.04E+00
0.00E+00
0.00E+00

Upp1
3
10
0.722
0.009
1.04E+00
0.00E+00
0.00E+00

Vps37b
3
10
0.607
0.074
1.03E+00
0.00E+00
0.00E+00

Bhlhe40
3
10
0.688
0.04
1.00E+00
0.00E+00
0.00E+00

Tcrg-C1
3
10
0.637
0.009
9.92E−01
0.00E+00
0.00E+00

Ikzf2
3
10
0.705
0.009
9.89E−01
0.00E+00
0.00E+00

Ffar2
3
10
0.693
0.009
9.88E−01
0.00E+00
0.00E+00

Ncoa7
3
10
0.687
0.074
9.61E−01
0.00E+00
0.00E+00

Txk
3
10
0.747
0.03
9.42E−01
0.00E+00
0.00E+00

Serpina3g
3
10
0.578
0.014
9.34E−01
0.00E+00
0.00E+00

Ctsw
3
10
0.705
0.018
9.21E−01
0.00E+00
0.00E+00

Bcl2
3
10
0.602
0.05
8.89E−01
0.00E+00
0.00E+00

Nabp1
3
10
0.569
0.04
8.35E−01
0.00E+00
0.00E+00

Sla
3
10
0.629
0.05
8.30E−01
0.00E+00
0.00E+00

S100a11
3
10
0.707
0.09
8.06E−01
0.00E+00
0.00E+00

Gpr183
3
10
0.635
0.048
7.69E−01
0.00E+00
0.00E+00

Maff
3
10
0.508
0.009
7.23E−01
0.00E+00
0.00E+00

Podnl1
3
10
0.625
0.008
7.07E−01
0.00E+00
0.00E+00

St6galnac3
3
10
0.633
0.019
7.04E−01
0.00E+00
0.00E+00

Il18r1
3
10
0.592
0.005
6.98E−01
0.00E+00
0.00E+00

Prr29
3
10
0.51
0.007
6.75E−01
0.00E+00
0.00E+00

Chad
3
10
0.55
0.005
6.73E−01
0.00E+00
0.00E+00

Asb2
3
10
0.507
0.01
6.57E−01
0.00E+00
0.00E+00

Maf
3
10
0.527
0.01
6.39E−01
0.00E+00
0.00E+00

Ptpn22
3
10
0.552
0.024
6.18E−01
0.00E+00
0.00E+00

Cd160
3
10
0.503
0.005
5.94E−01
0.00E+00
0.00E+00

Il2rb
3
10
0.514
0.021
5.82E−01
0.00E+00
0.00E+00

Tnfrsf25
3
10
0.527
0.011
5.76E−01
0.00E+00
0.00E+00

Skap1
3
10
0.5
0.035
5.09E−01
4.43E−306
7.85E−299

Gpr132
3
10
0.506
0.025
5.69E−01
1.88E−305
3.32E−298

Ccnd2
3
10
0.501
0.044
5.65E−01
2.22E−282
3.93E−275

Tnfaip3
3
10
0.518
0.07
6.70E−01
3.65E−282
6.46E−275

Runx3
3
10
0.518
0.049
5.27E−01
3.49E−277
6.17E−270

Ahcyl2
3
10
0.584
0.095
5.88E−01
1.87E−273
3.31E−266

Nfkbiz
3
10
0.511
0.082
6.08E−01
2.20E−254
3.90E−247

Prr29
3
11
0.51
0.026
6.44E−01
2.46E−199
4.35E−192

Car2
3
12
0.915
0.1
1.48E+00
0.00E+00
0.00E+00

Klrk1
3
12
0.742
0.059
1.06E+00
0.00E+00
0.00E+00

Upp1
3
12
0.722
0.039
1.00E+00
0.00E+00
0.00E+00

Ncr1
3
12
0.709
0.076
9.46E−01
2.27E−278
4.03E−271

Ncoa7
3
12
0.687
0.096
9.31E−01
3.69E−246
6.53E−239

Il18r1
3
12
0.592
0.07
6.10E−01
8.42E−191
1.49E−183

Chad
3
12
0.55
0.072
6.07E−01
5.93E−169
1.05E−161

Prr29
3
12
0.51
0.054
6.21E−01
3.24E−165
5.74E−158

Cxcr6
3
14
0.935
0.091
1.52E+00
1.09E−274
1.92E−267

Upp1
3
14
0.722
0.052
9.88E−01
3.46E−173
6.12E−166

Ncr1
3
14
0.709
0.077
9.39E−01
2.37E−171
4.20E−164

Tmem176b
3
17
0.975
0.094
1.74E+00
0.00E+00
0.00E+00

Serpinb1a
3
17
0.777
0.026
1.30E+00
5.39E−195
9.53E−188

Upp1
3
17
0.722
0.009
1.04E+00
4.52E−171
8.01E−164

Ffar2
3
17
0.693
0.009
9.78E−01
3.09E−158
5.47E−151

Tmem176b
3
18
0.975
0.032
1.84E+00
0.00E+00
0.00E+00

Tmem176a
3
18
0.952
0.011
1.69E+00
7.52E−299
1.33E−291

Lgals3
3
18
0.938
0.025
1.71E+00
4.73E−275
8.37E−268

Cxcr6
3
18
0.935
0.06
1.57E+00
1.03E−253
1.82E−246

Car2
3
18
0.915
0.028
1.59E+00
1.22E−247
2.17E−240

Fcer1g
3
18
0.904
0.05
1.50E+00
2.29E−229
4.06E−222

Lmo4
3
18
0.86
0.089
1.36E+00
3.31E−171
5.86E−164

Serpinb1a
3
18
0.777
0.018
1.31E+00
5.90E−164
1.04E−156

Tmem176b
3
19
0.975
0.096
1.77E+00
8.87E−200
1.57E−192

Tmem176a
3
19
0.952
0.052
1.65E+00
1.42E−185
2.52E−178

Lgals3
3
19
0.938
0.076
1.63E+00
3.13E−161
5.54E−154

Id2
3
20
0.824
0.059
1.41E+00
1.24E−160
2.19E−153

Cxcr6
3
22
0.935
0.086
1.54E+00
2.08E−206
3.69E−199

Cxcr6
3
24
0.935
0.049
1.56E+00
5.53E−210
9.78E−203

Sepp1
3
24
0.904
0.09
1.35E+00
6.20E−174
1.10E−166

Gimap3
3
24
0.88
0.049
1.21E+00
3.21E−165
5.69E−158

Cxcr6
3
25
0.935
0.054
1.56E+00
1.35E−189
2.40E−182

Lgals3
3
25
0.938
0.086
1.65E+00
1.46E−189
2.59E−182

Car2
3
25
0.915
0.054
1.49E+00
4.23E−172
7.49E−165

Il7r
3
25
0.911
0.081
1.40E+00
2.80E−161
4.96E−154

Emb
3
25
0.914
0.086
1.32E+00
9.93E−160
1.76E−152

Tmem176b
3
26
0.975
0.101
1.75E+00
6.96E−260
1.23E−252

Cxcr6
3
26
0.935
0.055
1.54E+00
1.21E−199
2.15E−192

Tmem176b
3
29
0.975
0.047
1.81E+00
9.29E−181
1.64E−173

Tmem176a
3
29
0.952
0.034
1.67E+00
5.29E−161
9.37E−154

Tmem176a
4
5
0.979
0.018
1.97E+00
0.00E+00
0.00E+00

Tmem176b
4
5
0.976
0.016
1.95E+00
0.00E+00
0.00E+00

S100a4
4
5
0.884
0.006
1.83E+00
0.00E+00
0.00E+00

Fcer1g
4
5
0.98
0.02
1.82E+00
0.00E+00
0.00E+00

Gem
4
5
0.777
0.028
1.72E+00
0.00E+00
0.00E+00

Nr4a1
4
5
0.774
0.095
1.43E+00
0.00E+00
0.00E+00

Ckb
4
5
0.891
0.022
1.42E+00
0.00E+00
0.00E+00

Fosb
4
5
0.623
0.011
1.32E+00
0.00E+00
0.00E+00

Cd83
4
5
0.578
0.037
1.27E+00
0.00E+00
0.00E+00

Lgals3
4
5
0.742
0.012
1.25E+00
0.00E+00
0.00E+00

Ncoa7
4
5
0.798
0.048
1.22E+00
0.00E+00
0.00E+00

Gadd45b
4
5
0.623
0.051
1.22E+00
0.00E+00
0.00E+00

Lmo4
4
5
0.817
0.101
1.17E+00
0.00E+00
0.00E+00

Prr29
4
5
0.784
0.002
1.15E+00
0.00E+00
0.00E+00

Car2
4
5
0.803
0.041
1.15E+00
0.00E+00
0.00E+00

Sdc4
4
5
0.748
0.004
1.12E+00
0.00E+00
0.00E+00

Bhlhe40
4
5
0.709
0.015
1.11E+00
0.00E+00
0.00E+00

Rasl11a
4
5
0.603
0.002
1.10E+00
0.00E+00
0.00E+00

Rora
4
5
0.73
0.016
1.03E+00
0.00E+00
0.00E+00

Chad
4
5
0.724
0.003
9.89E−01
0.00E+00
0.00E+00

Cited4
4
5
0.614
0.003
9.82E−01
0.00E+00
0.00E+00

Nrgn
4
5
0.719
0.004
9.65E−01
0.00E+00
0.00E+00

Maff
4
5
0.631
0.023
9.24E−01
0.00E+00
0.00E+00

Cd81
4
5
0.65
0.035
9.17E−01
0.00E+00
0.00E+00

Dhrs3
4
5
0.674
0.009
8.22E−01
0.00E+00
0.00E+00

Serpinb1a
4
5
0.606
0.01
8.13E−01
0.00E+00
0.00E+00

Fam110a
4
5
0.55
0.011
8.09E−01
0.00E+00
0.00E+00

Ffar2
4
5
0.563
0.002
7.72E−01
0.00E+00
0.00E+00

Ccr6
4
5
0.618
0.003
7.34E−01
0.00E+00
0.00E+00

Espn
4
5
0.591
0.008
7.30E−01
0.00E+00
0.00E+00

Rorc
4
5
0.557
0.003
6.76E−01
0.00E+00
0.00E+00

Kit
4
5
0.551
0.005
6.47E−01
0.00E+00
0.00E+00

Serpina3g
4
5
0.543
0.005
8.53E−01
1.9E−313
3.38E−306

Upp1
4
5
0.507
0.001
7.04E−01
3.2E−313
5.80E−306

Tnfrsf25
4
5
0.607
0.034
6.52E−01
7.1E−313
1.27E−305

Hebp1
4
5
0.565
0.013
8.70E−01
0.00E+00
3.61E−302

S100a6
4
5
0.553
0.019
1.02E+00
1.72E−294
3.05E−287

St6galnac3
4
5
0.529
0.022
5.66E−01
3.73E−294
6.61E−287

Podnl1
4
5
0.606
0.042
6.73E−01
3.90E−287
6.91E−280

Asb2
4
5
0.504
0.006
6.39E−01
7.62E−284
1.35E−276

Igfbp7
4
5
0.515
0.005
7.54E−01
9.67E−280
1.71E−272

Ube2e3
4
5
0.589
0.049
6.87E−01
2.18E−273
3.87E−266

Ptms
4
5
0.618
0.05
7.02E−01
8.80E−265
1.56E−257

Acot7
4
5
0.573
0.037
6.36E−01
6.45E−254
1.14E−246

Dgat1
4
5
0.504
0.025
6.34E−01
1.02E−248
1.81E−241

Egr1
4
5
0.526
0.055
9.05E−01
2.39E−244
4.23E−237

Il18r1
4
5
0.548
0.065
5.74E−01
8.58E−226
1.52E−218

Samsn1
4
5
0.543
0.06
5.85E−01
1.32E−212
2.34E−205

Cmc2
4
5
0.562
0.1
5.33E−01
6.39E−176
1.13E−168

S100a4
4
6
0.884
0.085
1.74E+00
0.00E+00
0.00E+00

Id2
4
6
0.854
0.096
1.56E+00
0.00E+00
0.00E+00

Cxcr6
4
6
0.861
0.078
1.26E+00
0.00E+00
0.00E+00

Prr29
4
6
0.784
0.02
1.13E+00
0.00E+00
0.00E+00

Rasl11a
4
6
0.603
0.023
1.08E+00
0.00E+00
0.00E+00

Car2
4
6
0.803
0.101
1.07E+00
0.00E+00
0.00E+00

Rora
4
6
0.73
0.09
9.45E−01
0.00E+00
0.00E+00

Cited4
4
6
0.614
0.043
9.36E−01
0.00E+00
0.00E+00

Chad
4
6
0.724
0.051
9.35E−01
0.00E+00
0.00E+00

Nrgn
4
6
0.719
0.04
9.26E−01
0.00E+00
0.00E+00

Cd81
4
6
0.65
0.031
9.17E−01
0.00E+00
0.00E+00

Dhrs3
4
6
0.674
0.04
7.90E−01
0.00E+00
0.00E+00

Espn
4
6
0.591
0.025
7.13E−01
0.00E+00
0.00E+00

Igfbp7
4
6
0.515
0.053
7.06E−01
0.00E+00
0.00E+00

Podnl1
4
6
0.606
0.047
6.67E−01
0.00E+00
0.00E+00

Tnfrsf25
4
6
0.607
0.027
6.58E−01
0.00E+00
0.00E+00

Acot7
4
6
0.573
0.062
6.12E−01
0.00E+00
0.00E+00

Serpinb1a
4
6
0.606
0.062
7.56E−01
2.3E−315
4.18E−308

Rorc
4
6
0.557
0.034
6.43E−01
l.OE−313
1.85E−306

Tcf7
4
6
0.617
0.058
6.93E−01
1.1E−311
2.00E−304

Serpina3g
4
6
0.543
0.064
7.94E−01
1.48E−301
2.62E−294

Upp1
4
6
0.507
0.044
6.57E−01
1.60E−284
2.84E−277

Asb2
4
6
0.504
0.05
5.92E−01
1.76E−279
3.11E−272

Maff
4
6
0.631
0.072
8.70E−01
2.21E−273
3.91E−266

St6galnac3
4
6
0.529
0.033
5.53E−01
3.37E−264
5.97E−257

Trbc2
4
6
0.544
0.084
9.70E−01
2.49E−262
4.40E−255

Il18r1
4
6
0.548
0.048
5.90E−01
2.56E−251
4.53E−244

Txk
4
6
0.564
0.076
6.13E−01
4.15E−247
7.36E−240

Kit
4
6
0.551
0.082
5.65E−01
5.62E−233
9.96E−226

Tmem176a
4
7
0.979
0.021
1.96E+00
0.00E+00
0.00E+00

Tmem176b
4
7
0.976
0.031
1.92E+00
0.00E+00
0.00E+00

Fcer1g
4
7
0.98
0.019
1.82E+00
0.00E+00
0.00E+00

S100a4
4
7
0.884
0.063
1.68E+00
0.00E+00
0.00E+00

Gem
4
7
0.777
0.088
1.64E+00
0.00E+00
0.00E+00

Fosb
4
7
0.623
0.023
1.31E+00
0.00E+00
0.00E+00

Lgals3
4
7
0.742
0.03
1.21E+00
0.00E+00
0.00E+00

Cxcr6
4
7
0.861
0.099
1.20E+00
0.00E+00
0.00E+00

Car2
4
7
0.803
0.019
1.16E+00
0.00E+00
0.00E+00

Prr29
4
7
0.784
0.001
1.15E+00
0.00E+00
0.00E+00

Sdc4
4
7
0.748
0.041
1.08E+00
0.00E+00
0.00E+00

Rasl11a
4
7
0.603
0.028
1.07E+00
0.00E+00
0.00E+00

Chad
4
7
0.724
0.005
9.87E−01
0.00E+00
0.00E+00

Cited4
4
7
0.614
0.006
9.76E−01
0.00E+00
0.00E+00

Maff
4
7
0.631
0.052
8.78E−01
0.00E+00
0.00E+00

Nrgn
4
7
0.719
0.042
8.74E−01
0.00E+00
0.00E+00

Hebp1
4
7
0.565
0.016
8.67E−01
0.00E+00
0.00E+00

Serpinb1a
4
7
0.606
0.022
7.97E−01
0.00E+00
0.00E+00

Serpina3g
4
7
0.543
0.045
7.83E−01
0.00E+00
0.00E+00

Fam110a
4
7
0.55
0.049
7.65E−01
0.00E+00
0.00E+00

Ffar2
4
7
0.563
0.014
7.54E−01
0.00E+00
0.00E+00

Igfbp7
4
7
0.515
0.01
7.45E−01
0.00E+00
0.00E+00

Upp1
4
7
0.507
0.004
7.01E−01
0.00E+00
0.00E+00

Espn
4
7
0.591
0.043
6.93E−01
0.00E+00
0.00E+00

Ccr6
4
7
0.618
0.052
6.75E−01
0.00E+00
0.00E+00

Rorc
4
7
0.557
0.019
6.58E−01
0.00E+00
0.00E+00

Kit
4
7
0.551
0.006
6.44E−01
0.00E+00
0.00E+00

Il18r1
4
7
0.548
0.034
6.04E−01
0.00E+00
0.00E+00

Ube2e3
4
7
0.589
0.094
6.32E−01
8.0E−313
1.42E−305

Dgat1
4
7
0.504
0.063
5.90E−01
3.12E−273
5.52E−266

Runx3
4
7
0.508
0.101
4.70E−01
6.20E−216
1.10E−208

S100a4
4
8
0.884
0.101
1.65E+00
0.00E+00
0.00E+00

Cxcr6
4
8
0.861
0.085
1.26E+00
0.00E+00
0.00E+00

Ncoa7
4
8
0.798
0.08
1.18E+00
0.00E+00
0.00E+00

Prr29
4
8
0.784
0.008
1.14E+00
0.00E+00
0.00E+00

Rasl11a
4
8
0.603
0.019
1.08E+00
0.00E+00
0.00E+00

Chad
4
8
0.724
0.042
9.48E−01
0.00E+00
0.00E+00

Cd81
4
8
0.65
0.027
9.21E−01
0.00E+00
0.00E+00

Hebp1
4
8
0.565
0.025
8.58E−01
0.00E+00
0.00E+00

Ffar2
4
8
0.563
0.021
7.50E−01
0.00E+00
0.00E+00

Serpinb1a
4
8
0.606
0.052
7.43E−01
0.00E+00
0.00E+00

Ccr6
4
8
0.618
0.019
7.17E−01
0.00E+00
0.00E+00

Espn
4
8
0.591
0.027
7.10E−01
0.00E+00
0.00E+00

Rorc
4
8
0.557
0.025
6.54E−01
0.00E+00
0.00E+00

Tnfrsf25
4
8
0.607
0.048
6.34E−01
0.00E+00
0.00E+00

Fosb
4
8
0.623
0.091
1.18E+00
2.12E−305
3.76E−298

Upp1
4
8
0.507
0.026
6.78E−01
5.62E−296
9.96E−289

Igfbp7
4
8
0.515
0.032
7.20E−01
2.28E−288
4.04E−281

Fam110a
4
8
0.55
0.053
7.49E−01
4.44E−285
7.86E−278

Anxa5
4
8
0.609
0.088
6.17E−01
4.30E−283
7.62E−276

Rgs10
4
8
0.564
0.099
5.69E−01
2.60E−228
4.60E−221

Asb2
4
8
0.504
0.088
5.43E−01
1.25E−194
2.21E−187

Tmem176a
4
9
0.979
0.034
1.95E+00
0.00E+00
0.00E+00

Tmem176b
4
9
0.976
0.039
1.92E+00
0.00E+00
0.00E+00

Cd7
4
9
0.876
0.077
1.81E+00
0.00E+00
0.00E+00

S100a4
4
9
0.884
0.02
1.81E+00
0.00E+00
0.00E+00

Fcer1g
4
9
0.98
0.038
1.80E+00
0.00E+00
0.00E+00

Il7r
4
9
0.951
0.043
1.59E+00
0.00E+00
0.00E+00

Ckb
4
9
0.891
0.052
1.38E+00
0.00E+00
0.00E+00

Cxcr6
4
9
0.861
0.017
1.34E+00
0.00E+00
0.00E+00

Bcl2
4
9
0.85
0.095
1.24E+00
0.00E+00
0.00E+00

Lgals3
4
9
0.742
0.035
1.21E+00
0.00E+00
0.00E+00

Prr29
4
9
0.784
0.008
1.14E+00
0.00E+00
0.00E+00

S100a10
4
9
0.824
0.093
1.14E+00
0.00E+00
0.00E+00

Ramp1
4
9
0.719
0.053
1.04E+00
6.49E−304
1.15E−296

Sdc4
4
9
0.748
0.038
1.07E+00
1.97E−283
3.48E−276

Chad
4
9
0.724
0.009
9.83E−01
5.16E−265
9.14E−258

Bst2
4
9
0.687
0.099
7.89E−01
6.89E−259
1.22E−251

Cited4
4
9
0.614
0.009
9.72E−01
8.64E−251
1.53E−243

Rora
4
9
0.73
0.013
1.04E+00
4.19E−243
7.43E−236

Sla
4
9
0.697
0.063
1.01E+00
1.41E−239
2.50E−232

Igfbp7
4
9
0.515
0.01
7.49E−01
1.42E−239
2.52E−232

S100a6
4
9
0.553
0.029
1.00E+00
1.52E−235
2.69E−228

Gpr183
4
9
0.675
0.07
8.23E−01
1.14E−234
2.02E−227

Hebp1
4
9
0.565
0.024
8.60E−01
9.49E−234
1.68E−226

Podnl1
4
9
0.606
0.016
7.01E−01
5.77E−230
1.02E−222

Tnfrsf25
4
9
0.607
0.012
6.74E−01
5.55E−228
9.83E−221

Bhlhe40
4
9
0.709
0.05
1.06E+00
4.15E−226
7.35E−219

Ffar2
4
9
0.563
0.014
7.57E−01
5.97E−226
1.06E−218

Serpina3g
4
9
0.543
0.021
8.35E−01
8.93E−226
1.58E−218

Rorc
4
9
0.557
0.006
6.71E−01
2.53E−224
4.48E−217

Rasl11a
4
9
0.603
0.004
1.10E+00
7.17E−221
1.27E−213

Ccr6
4
9
0.618
0.015
7.19E−01
6.70E−205
1.19E−197

Tcf7
4
9
0.617
0.052
6.98E−01
1.71E−203
3.03E−196

Anxa5
4
9
0.609
0.077
6.29E−01
5.35E−203
9.46E−196

Gpr132
4
9
0.66
0.038
8.02E−01
1.11E−200
1.96E−193

Asb2
4
9
0.504
0.025
6.13E−01
1.60E−197
2.83E−190

Espn
4
9
0.591
0.023
7.16E−01
3.83E−197
6.79E−190

Serpinb1a
4
9
0.606
0.067
7.16E−01
2.30E−194
4.08E−187

Upp1
4
9
0.507
0.015
6.89E−01
2.77E−191
4.90E−184

Maff
4
9
0.631
0.015
9.33E−01
8.58E−187
1.52E−179

Il18r1
4
9
0.548
0.009
6.35E−01
1.22E−178
2.17E−171

Kit
4
9
0.551
0.007
6.43E−01
1.46E−175
2.58E−168

Runx3
4
9
0.508
0.097
4.57E−01
5.54E−169
9.81E−162

Dgat1
4
9
0.504
0.042
6.19E−01
2.01E−167
3.56E−160

St6galnac3
4
9
0.529
0.019
5.69E−01
8.27E−160
1.46E−152

Txk
4
9
0.564
0.055
6.34E−01
4.75E−159
8.41E−152

Tmem176a
4
10
0.979
0.023
1.96E+00
0.00E+00
0.00E+00

Tmem176b
4
10
0.976
0.025
1.92E+00
0.00E+00
0.00E+00

Cd7
4
10
0.876
0.043
1.84E+00
0.00E+00
0.00E+00

S100a4
4
10
0.884
0.014
1.83E+00
0.00E+00
0.00E+00

Fcer1g
4
10
0.98
0.032
1.80E+00
0.00E+00
0.00E+00

Id2
4
10
0.854
0.051
1.61E+00
0.00E+00
0.00E+00

Il7r
4
10
0.951
0.026
1.60E+00
0.00E+00
0.00E+00

Sepp1
4
10
0.944
0.075
1.42E+00
0.00E+00
0.00E+00

Ckb
4
10
0.891
0.027
1.42E+00
0.00E+00
0.00E+00

Nr4a1
4
10
0.774
0.093
1.41E+00
0.00E+00
0.00E+00

Cxcr6
4
10
0.861
0.013
1.34E+00
0.00E+00
0.00E+00

Bcl2
4
10
0.85
0.05
1.30E+00
0.00E+00
0.00E+00

Fosb
4
10
0.623
0.041
1.28E+00
0.00E+00
0.00E+00

Lgals3
4
10
0.742
0.03
1.22E+00
0.00E+00
0.00E+00

S100a10
4
10
0.824
0.053
1.20E+00
0.00E+00
0.00E+00

Ncoa7
4
10
0.798
0.074
1.19E+00
0.00E+00
0.00E+00

Emb
4
10
0.846
0.057
1.17E+00
0.00E+00
0.00E+00

Prr29
4
10
0.784
0.007
1.14E+00
0.00E+00
0.00E+00

Rasl11a
4
10
0.603
0.005
1.10E+00
0.00E+00
0.00E+00

Ramp1
4
10
0.719
0.019
1.08E+00
0.00E+00
0.00E+00

Car2
4
10
0.803
0.1
1.08E+00
0.00E+00
0.00E+00

Bhlhe40
4
10
0.709
0.04
1.07E+00
0.00E+00
0.00E+00

Sdc4
4
10
0.748
0.044
1.05E+00
0.00E+00
0.00E+00

Rora
4
10
0.73
0.008
1.04E+00
0.00E+00
0.00E+00

S100a6
4
10
0.553
0.01
1.03E+00
0.00E+00
0.00E+00

Sla
4
10
0.697
0.05
1.02E+00
0.00E+00
0.00E+00

Chad
4
10
0.724
0.005
9.84E−01
0.00E+00
0.00E+00

Cited4
4
10
0.614
0.006
9.76E−01
0.00E+00
0.00E+00

Maff
4
10
0.631
0.009
9.38E−01
0.00E+00
0.00E+00

Hebp1
4
10
0.565
0.016
8.67E−01
0.00E+00
0.00E+00

Gpr183
4
10
0.675
0.048
8.46E−01
0.00E+00
0.00E+00

Serpina3g
4
10
0.543
0.014
8.44E−01
0.00E+00
0.00E+00

Bst2
4
10
0.687
0.051
8.44E−01
0.00E+00
0.00E+00

Selplg
4
10
0.712
0.09
8.21E−01
0.00E+00
0.00E+00

Gpr132
4
10
0.66
0.025
8.18E−01
0.00E+00
0.00E+00

Ffar2
4
10
0.563
0.009
7.63E−01
0.00E+00
0.00E+00

Igfbp7
4
10
0.515
0.012
7.47E−01
0.00E+00
0.00E+00

Tcf7
4
10
0.617
0.029
7.29E−01
0.00E+00
0.00E+00

Ccr6
4
10
0.618
0.014
7.20E−01
0.00E+00
0.00E+00

Podnl1
4
10
0.606
0.008
7.08E−01
0.00E+00
0.00E+00

Espn
4
10
0.591
0.029
7.08E−01
0.00E+00
0.00E+00

Upp1
4
10
0.507
0.009
6.97E−01
0.00E+00
0.00E+00

Tnfrsf25
4
10
0.607
0.011
6.76E−01
0.00E+00
0.00E+00

Rorc
4
10
0.557
0.002
6.76E−01
0.00E+00
0.00E+00

Znrf1
4
10
0.632
0.057
6.75E−01
0.00E+00
0.00E+00

Anxa5
4
10
0.609
0.043
6.67E−01
0.00E+00
0.00E+00

Txk
4
10
0.564
0.03
6.66E−01
0.00E+00
0.00E+00

Kit
4
10
0.551
0.007
6.44E−01
0.00E+00
0.00E+00

Il18r1
4
10
0.548
0.005
6.38E−01
0.00E+00
0.00E+00

Asb2
4
10
0.504
0.01
6.34E−01
0.00E+00
0.00E+00

St6galnac3
4
10
0.529
0.019
5.68E−01
0.00E+00
0.00E+00

Acot7
4
10
0.573
0.099
5.72E−01
2.1E−316
0.00E+00

Serpinb1a
4
10
0.606
0.088
6.82E−01
3.77E−307
6.68E−300

S100a11
4
10
0.563
0.09
6.10E−01
3.58E−302
6.34E−295

Tnfaip3
4
10
0.573
0.07
7.74E−01
1.16E−298
2.05E−291

Vps37b
4
10
0.549
0.074
9.19E−01
2.39E−275
4.23E−268

Runx3
4
10
0.508
0.049
5.35E−01
2.40E−275
4.25E−268

Hcst
4
10
0.511
0.089
5.47E−01
8.65E−248
1.53E−240

Prr29
4
11
0.784
0.026
1.11E+00
0.00E+00
0.00E+00

Cd81
4
11
0.65
0.042
8.99E−01
3.13E−256
5.54E−249

Ccr6
4
11
0.618
0.032
7.01E−01
2.96E−246
5.24E−239

Rasl11a
4
11
0.603
0.038
1.06E+00
1.56E−229
2.77E−222

Hebp1
4
11
0.565
0.044
8.35E−01
1.32E−195
2.33E−188

Rorc
4
11
0.557
0.052
6.21E−01
1.54E−181
2.73E−174

Igfbp7
4
11
0.515
0.041
7.13E−01
2.65E−166
4.69E−159

Ncoa7
4
12
0.798
0.096
1.16E+00
0.00E+00
0.00E+00

Prr29
4
12
0.784
0.054
1.09E+00
0.00E+00
0.00E+00

Chad
4
12
0.724
0.072
9.18E−01
8.94E−278
1.58E−270

Sdc4
4
12
0.748
0.095
1.02E+00
4.64E−275
8.21E−268

Ccr6
4
12
0.618
0.02
7.15E−01
6.12E−252
1.08E−244

Rasl11a
4
12
0.603
0.041
1.04E+00
1.99E−216
3.52E−209

Hebp1
4
12
0.565
0.042
8.35E−01
8.58E−194
1.52E−186

Rorc
4
12
0.557
0.044
6.31E−01
2.96E−186
5.24E−179

Upp1
4
12
0.507
0.039
6.61E−01
1.53E−164
2.71E−157

Igfbp7
4
12
0.515
0.045
6.86E−01
4.77E−160
8.44E−153

Cxcr6
4
14
0.861
0.091
1.22E+00
6.27E−239
1.11E−231

Prr29
4
14
0.784
0.063
9.79E−01
1.67E−222
2.95E−215

Chad
4
14
0.724
0.078
9.04E−01
9.40E−171
1.66E−163

Tmem176a
4
17
0.979
0.059
1.91E+00
0.00E+00
0.00E+00

Tmem176b
4
17
0.976
0.094
1.83E+00
0.00E+00
0.00E+00

S100a4
4
17
0.884
0.012
1.83E+00
9.45E−277
1.67E−269

Prr29
4
17
0.784
0.006
1.14E+00
2.32E−207
4.11E−200

Sdc4
4
17
0.748
0.023
1.10E+00
1.01E−170
1.78E−163

Ncoa7
4
17
0.798
0.094
1.16E+00
2.00E−162
3.54E−155

Ramp1
4
17
0.719
0.032
1.05E+00
2.36E−159
4.18E−152

Tmem176a
4
18
0.979
0.011
1.98E+00
0.00E+00
0.00E+00

S100a4
4
18
0.884
0.028
1.79E+00
9.91E−215
1.75E−207

Cd7
4
18
0.876
0.05
1.84E+00
2.91E−195
5.15E−188

Ckb
4
18
0.891
0.1
1.34E+00
1.20E−194
2.13E−187

Cxcr6
4
18
0.861
0.06
1.26E+00
2.34E−179
4.14E−172

Prr29
4
18
0.784
0.004
1.15E+00
9.47E−171
1.68E−163

Car2
4
18
0.803
0.028
1.16E+00
2.62E−160
4.64E−153

Tmem176a
4
19
0.979
0.052
1.93E+00
1.02E−193
1.81E−186

Tmem176b
4
19
0.976
0.096
1.87E+00
2.33E−175
4.12E−168

Id2
4
20
0.854
0.059
1.47E+00
1.98E−183
3.50E−176

Prr29
4
20
0.784
0.025
1.13E+00
1.18E−165
2.09E−158

Prr29
4
22
0.784
0.022
1.12E+00
1.40E−168
2.48E−161

Cxcr6
4
22
0.861
0.086
1.24E+00
3.90E−164
6.90E−157

Sepp1
4
24
0.944
0.09
1.41E+00
5.72E−219
1.01E−211

Cxcr6
4
24
0.861
0.049
1.26E+00
1.18E−169
2.09E−162

Bcl2
4
24
0.85
0.094
1.15E+00
9.74E−163
1.72E−155

Fcer1g
4
25
0.98
0.086
1.71E+00
1.44E−228
2.56E−221

Il7r
4
25
0.951
0.081
1.51E+00
2.87E−186
5.07E−179

Tmem176b
4
26
0.976
0.101
1.84E+00
1.93E−273
3.41E−266

S100a4
4
26
0.884
0.051
1.78E+00
6.55E−191
1.16E−183

Ckb
4
26
0.891
0.097
1.33E+00
4.88E−179
8.64E−172

Tmem176a
4
29
0.979
0.034
1.96E+00
8.35E−204
1.48E−196

Tmem176b
4
29
0.976
0.047
1.90E+00
1.75E−193
3.10E−186

Fcer1g
4
29
0.98
0.027
1.78E+00
2.57E−174
4.54E−167

Fcer1g
4
30
0.98
0.074
1.73E+00
1.68E−162
2.97E−155

Tmem176a
4
30
0.979
0.081
1.91E+00
1.28E−161
2.27E−154

Trbc2
5
6
0.958
0.084
1.80E+00
0.00E+00
0.00E+00

Ms4a4b
5
6
0.935
0.057
1.49E+00
0.00E+00
0.00E+00

Cd3d
5
6
0.934
0.026
1.40E+00
0.00E+00
0.00E+00

Cd3g
5
6
0.942
0.024
1.39E+00
0.00E+00
0.00E+00

Cd3e
5
6
0.912
0.02
1.29E+00
0.00E+00
0.00E+00

Lef1
5
6
0.818
0.011
1.10E+00
0.00E+00
0.00E+00

Trac
5
6
0.796
0.013
1.10E+00
0.00E+00
0.00E+00

Lck
5
6
0.802
0.098
9.17E−01
0.00E+00
0.00E+00

Lat
5
6
0.797
0.098
9.15E−01
0.00E+00
0.00E+00

Thy1
5
6
0.793
0.092
9.78E−01
6.4E−316
0.00E+00

Skap1
5
6
0.706
0.033
7.74E−01
1.37E−278
2.43E−271

Igfbp4
5
6
0.555
0.014
8.95E−01
5.40E−273
9.57E−266

Dapl1
5
6
0.55
0.006
1.04E+00
1.26E−256
2.23E−249

Cd2
5
6
0.613
0.031
6.73E−01
1.79E−253
3.16E−246

Klk8
5
6
0.572
0.03
6.42E−01
2.89E−242
5.11E−235

Arl4c
5
6
0.626
0.062
6.86E−01
2.80E−232
4.95E−225

Trbc1
5
6
0.631
0.07
1.29E+00
1.70E−208
3.00E−201

Cd247
5
6
0.514
0.011
5.38E−01
2.34E−203
4.14E−196

Tcf7
5
6
0.555
0.058
5.79E−01
3.71E−177
6.57E−170

Dusp2
5
6
0.5
0.098
6.04E−01
3.25E−168
5.76E−161

Txk
5
6
0.547
0.076
5.71E−01
3.11E−162
5.50E−155

Cd8b1
5
7
0.947
0.082
1.49E+00
0.00E+00
0.00E+00

Cd8a
5
7
0.799
0.035
1.00E+00
0.00E+00
0.00E+00

Nkg7
5
7
0.818
0.095
9.24E−01
0.00E+00
0.00E+00

Dapl1
5
7
0.55
0.047
8.85E−01
0.00E+00
0.00E+00

Igfbp4
5
7
0.555
0.058
7.98E−01
0.00E+00
0.00E+00

Cd8b1
5
8
0.947
0.033
1.63E+00
0.00E+00
0.00E+00

Cd3e
5
8
0.912
0.016
1.30E+00
0.00E+00
0.00E+00

Cd8a
5
8
0.799
0.014
1.07E+00
0.00E+00
0.00E+00

Trac
5
8
0.796
0.056
1.05E+00
0.00E+00
0.00E+00

Dapl1
5
8
0.55
0.001
1.04E+00
0.00E+00
0.00E+00

Igfbp4
5
8
0.555
0.013
8.79E−01
0.00E+00
0.00E+00

Rgs10
5
8
0.626
0.099
6.67E−01
0.00E+00
0.00E+00

Klk8
5
8
0.572
0.076
5.86E−01
0.00E+00
0.00E+00

Bcl2
5
9
0.762
0.095
1.27E+00
7.72E−296
1.37E−288

Nkg7
5
9
0.818
0.068
1.15E+00
3.37E−277
5.96E−270

Trac
5
9
0.796
0.083
1.02E+00
7.53E−267
1.33E−259

Lef1
5
9
0.818
0.057
1.04E+00
8.04E−257
1.42E−249

Thy1
5
9
0.793
0.086
9.90E−01
1.90E−238
3.37E−231

Cd8a
5
9
0.799
0.031
1.05E+00
4.61E−213
8.17E−206

Skap1
5
9
0.706
0.088
7.18E−01
2.66E−183
4.71E−176

Igfbp4
5
9
0.555
0.066
8.38E−01
1.30E−179
2.29E−172

Arl4c
5
9
0.626
0.037
7.19E−01
4.23E−179
7.49E−172

Dapl1
5
9
0.55
0.036
1.01E+00
4.26E−167
7.54E−160

Satb1
5
9
0.618
0.069
6.56E−01
2.82E−164
4.98E−157

Sell
5
9
0.604
0.062
6.59E−01
8.62E−163
1.53E−155

Klk8
5
9
0.572
0.034
6.35E−01
1.97E−160
3.48E−153

S100a10
5
9
0.656
0.093
6.51E−01
3.53E−160
6.25E−153

Cd8b1
5
10
0.947
0.027
1.63E+00
0.00E+00
0.00E+00

Ms4a4b
5
10
0.935
0.07
1.48E+00
0.00E+00
0.00E+00

Cd3g
5
10
0.942
0.055
1.36E+00
0.00E+00
0.00E+00

Cd3d
5
10
0.934
0.083
1.35E+00
0.00E+00
0.00E+00

Bcl2
5
10
0.762
0.05
1.33E+00
0.00E+00
0.00E+00

Cd3e
5
10
0.912
0.07
1.25E+00
0.00E+00
0.00E+00

Nkg7
5
10
0.818
0.045
1.18E+00
0.00E+00
0.00E+00

Lef1
5
10
0.818
0.031
1.08E+00
0.00E+00
0.00E+00

Trac
5
10
0.796
0.05
1.07E+00
0.00E+00
0.00E+00

Cd8a
5
10
0.799
0.023
1.06E+00
0.00E+00
0.00E+00

Thy1
5
10
0.793
0.049
1.04E+00
0.00E+00
0.00E+00

Selplg
5
10
0.825
0.09
1.01E+00
0.00E+00
0.00E+00

Lat
5
10
0.797
0.076
9.57E−01
0.00E+00
0.00E+00

Ccnd2
5
10
0.75
0.044
9.54E−01
0.00E+00
0.00E+00

Hcst
5
10
0.782
0.089
9.37E−01
0.00E+00
0.00E+00

Ccr7
5
10
0.678
0.069
9.00E−01
0.00E+00
0.00E+00

Skap1
5
10
0.706
0.035
7.73E−01
0.00E+00
0.00E+00

Arl4c
5
10
0.626
0.017
7.42E−01
0.00E+00
0.00E+00

Igfbp4
5
10
0.555
0.037
8.78E−01
7.8E−317
0.00E+00

Sell
5
10
0.604
0.042
6.80E−01
2.0E−315
3.62E−308

Dapl1
5
10
0.55
0.013
1.03E+00
4.5E−315
8.06E−308

Satb1
5
10
0.618
0.061
6.64E−01
3.05E−300
5.40E−293

Fyb
5
10
0.633
0.059
6.85E−01
3.34E−299
5.92E−292

Trbc1
5
10
0.631
0.064
1.32E+00
2.06E−298
3.65E−291

Itgb7
5
10
0.608
0.058
6.22E−01
1.31E−284
2.31E−277

Cd2
5
10
0.613
0.074
6.13E−01
9.74E−273
1.72E−265

Ramp1
5
10
0.528
0.019
5.78E−01
7.85E−268
1.39E−260

Tcf7
5
10
0.555
0.029
6.15E−01
3.02E−264
5.34E−257

Txk
5
10
0.547
0.03
6.25E−01
1.63E−243
2.88E−236

Cd247
5
10
0.514
0.025
5.25E−01
6.23E−243
1.10E−235

Ifi203
5
10
0.515
0.023
5.53E−01
1.57E−230
2.77E−223

Fam189b
5
10
0.506
0.025
5.28E−01
1.71E−229
3.03E−222

Mndal
5
10
0.506
0.024
5.35E−01
1.07E−223
1.90E−216

Emp3
5
10
0.574
0.071
5.97E−01
2.13E−222
3.77E−215

H2-Q7
5
10
0.549
0.101
5.17E−01
1.25E−210
2.21E−203

Cd8b1
5
11
0.947
0.018
1.64E+00
0.00E+00
0.00E+00

Cd3d
5
11
0.934
0.047
1.37E+00
0.00E+00
0.00E+00

Cd3e
5
11
0.912
0.021
1.28E+00
0.00E+00
0.00E+00

Cd3g
5
11
0.942
0.069
1.27E+00
0.00E+00
0.00E+00

Lef1
5
11
0.818
0.058
1.05E+00
0.00E+00
0.00E+00

Cd8a
5
11
0.799
0.014
1.05E+00
0.00E+00
0.00E+00

Ccr7
5
11
0.678
0.035
9.49E−01
0.00E+00
0.00E+00

Dapl1
5
11
0.55
0
1.05E+00
9.92E−289
1.76E−281

Igfbp4
5
11
0.555
0.009
9.05E−01
7.67E−283
1.36E−275

Sell
5
11
0.604
0.094
6.14E−01
8.04E−216
1.42E−208

Cd8b1
5
12
0.947
0.03
1.62E+00
0.00E+00
0.00E+00

Ms4a4b
5
12
0.935
0.051
1.49E+00
0.00E+00
0.00E+00

Cd3d
5
12
0.934
0.028
1.40E+00
0.00E+00
0.00E+00

Cd3e
5
12
0.912
0.057
1.25E+00
0.00E+00
0.00E+00

Trac
5
12
0.796
0.014
1.10E+00
0.00E+00
0.00E+00

Cd8a
5
12
0.799
0.02
1.06E+00
0.00E+00
0.00E+00

Lef1
5
12
0.818
0.073
1.03E+00
0.00E+00
0.00E+00

Ms4a6b
5
12
0.799
0.08
9.20E−01
0.00E+00
0.00E+00

Ccr7
5
12
0.678
0.047
9.18E−01
5.14E−295
9.10E−288

Cd2
5
12
0.613
0.026
6.79E−01
1.75E−271
3.09E−264

Dapl1
5
12
0.55
0.003
1.04E+00
9.79E−262
1.73E−254

Arl4c
5
12
0.626
0.048
7.07E−01
1.32E−252
2.34E−245

Igfbp4
5
12
0.555
0.03
8.47E−01
2.74E−243
4.85E−236

Sell
5
12
0.604
0.081
6.35E−01
9.27E−220
1.64E−212

Cd247
5
12
0.514
0.027
5.20E−01
9.38E−193
1.66E−185

Cd3d
5
14
0.934
0.061
1.33E+00
1.69E−223
2.99E−216

Cd8b1
5
14
0.947
0.061
1.58E+00
1.25E−210
2.22E−203

Cd3e
5
14
0.912
0.038
1.24E+00
1.22E−208
2.15E−201

Cd3g
5
14
0.942
0.058
1.30E+00
2.71E−192
4.79E−185

Lat
5
14
0.797
0.053
9.52E−01
1.02E−187
1.80E−180

Trac
5
14
0.796
0.033
1.06E+00
8.61E−187
1.52E−179

Lef1
5
14
0.818
0.033
1.06E+00
2.95E−168
5.22E−161

Cd8a
5
14
0.799
0.019
1.06E+00
2.46E−164
4.35E−157

Thy1
5
14
0.793
0.085
9.85E−01
2.27E−162
4.01E−155

Cd8b1
5
15
0.947
0.008
1.65E+00
1.82E−197
3.22E−190

Cd3d
5
15
0.934
0.013
1.42E+00
2.40E−165
4.25E−158

Cd3g
5
15
0.942
0.04
1.36E+00
9.49E−165
1.68E−157

Cd8b1
5
17
0.947
0.062
1.52E+00
2.23E−258
3.95E−251

Lef1
5
17
0.818
0.062
1.03E+00
8.96E−196
1.59E−188

Cd8b1
5
20
0.947
0.064
1.59E+00
1.42E−204
2.52E−197

Cd3d
5
20
0.934
0.093
1.25E+00
2.63E−193
4.66E−186

Cd3e
5
20
0.912
0.064
1.18E+00
2.15E−191
3.80E−184

Cd3g
5
20
0.942
0.081
1.28E+00
1.05E−188
1.86E−181

Cd3d
5
22
0.934
0.022
1.41E+00
1.13E−183
2.00E−176

Cd8b1
5
22
0.947
0.043
1.62E+00
5.11E−174
9.05E−167

Cd3e
5
22
0.912
0.039
1.28E+00
1.04E−169
1.84E−162

Cd3g
5
22
0.942
0.039
1.37E+00
2.02E−166
3.58E−159

Cd8b1
5
24
0.947
0.031
1.62E+00
6.07E−184
1.07E−176

Ms4a4b
5
24
0.935
0.031
1.52E+00
1.46E−180
2.58E−173

Cd3e
5
24
0.912
0.004
1.32E+00
5.08E−180
8.99E−173

Cd3d
5
24
0.934
0.018
1.42E+00
4.87E−179
8.62E−172

Trbc2
5
24
0.958
0.081
1.76E+00
5.81E−171
1.03E−163

Cd3g
5
24
0.942
0.027
1.33E+00
3.96E−170
7.02E−163

Nkg7
5
24
0.818
0.076
1.10E+00
1.16E−163
2.05E−156

Coro1a
5
25
0.982
0.1
1.63E+00
5.40E−263
9.56E−256

Trbc2
5
25
0.958
0.063
1.81E+00
1.45E−233
2.56E−226

Limd2
5
25
0.951
0.1
1.46E+00
1.06E−232
1.88E−225

Cd3d
5
25
0.934
0.018
1.42E+00
1.37E−225
2.43E−218

Cd8b1
5
25
0.947
0.023
1.61E+00
2.35E−225
4.15E−218

Ms4a4b
5
25
0.935
0.018
1.54E+00
6.53E−221
1.16E−213

Cd3g
5
25
0.942
0.027
1.39E+00
1.93E−218
3.42E−211

Cd3e
5
25
0.912
0.009
1.31E+00
1.51E−212
2.67E−205

Ptprcap
5
25
0.844
0.063
1.11E+00
2.09E−160
3.69E−153

Ms4a4b
5
26
0.935
0.06
1.48E+00
2.56E−197
4.52E−190

Cd3d
5
26
0.934
0.032
1.39E+00
5.62E−191
9.95E−184

Cd3g
5
26
0.942
0.014
1.39E+00
1.36E−180
2.40E−173

Cd3e
5
26
0.912
0.078
1.22E+00
2.76E−180
4.89E−173

Trbc2
5
26
0.958
0.083
1.77E+00
8.90E−180
1.58E−172

Cd8b1
5
26
0.947
0.046
1.55E+00
9.54E−180
1.69E−172

Trbc2
5
30
0.958
0.059
1.82E+00
2.56E−158
4.53E−151

Cd52
5
32
0.992
0.094
2.05E+00
8.42E−188
1.49E−180

Coro1a
5
32
0.982
0.085
1.66E+00
4.24E−162
7.51E−155

Tyrobp
6
7
0.999
0.04
3.69E+00
0.00E+00
0.00E+00

Plac8
6
7
0.999
0.054
3.41E+00
0.00E+00
0.00E+00

Ccl4
6
7
0.868
0.016
3.40E+00
0.00E+00
0.00E+00

Ly6c2
6
7
0.997
0.015
3.18E+00
0.00E+00
0.00E+00

Irf8
6
7
0.997
0.07
3.02E+00
0.00E+00
0.00E+00

Siglech
6
7
0.998
0.008
2.78E+00
0.00E+00
0.00E+00

Klk1
6
7
0.96
0.01
2.68E+00
0.00E+00
0.00E+00

Ly6c1
6
7
0.991
0.007
2.62E+00
0.00E+00
0.00E+00

Cox6a2
6
7
0.969
0.005
2.48E+00
0.00E+00
0.00E+00

Rnase6
6
7
0.992
0.009
2.35E+00
0.00E+00
0.00E+00

Iglc3
6
7
0.968
0.055
2.34E+00
0.00E+00
0.00E+00

Ctsh
6
7
0.988
0.03
2.27E+00
0.00E+00
0.00E+00

Mpeg1
6
7
0.983
0.004
2.09E+00
0.00E+00
0.00E+00

Ctsl
6
7
0.96
0.098
2.01E+00
0.00E+00
0.00E+00

D13Ertd608e
6
7
0.924
0.001
1.94E+00
0.00E+00
0.00E+00

Pld4
6
7
0.975
0.013
1.94E+00
0.00E+00
0.00E+00

Tcf4
6
7
0.977
0.018
1.92E+00
0.00E+00
0.00E+00

Klk1b27
6
7
0.965
0.012
1.91E+00
0.00E+00
0.00E+00

Cybb
6
7
0.978
0.09
1.87E+00
0.00E+00
0.00E+00

Ccr9
6
7
0.956
0.09
1.76E+00
0.00E+00
0.00E+00

Slpi
6
7
0.789
0.013
1.68E+00
0.00E+00
0.00E+00

Clec12a
6
7
0.93
0.002
1.66E+00
0.00E+00
0.00E+00

Tsc22d1
6
7
0.908
0.032
1.64E+00
0.00E+00
0.00E+00

Mef2c
6
7
0.947
0.019
1.63E+00
0.00E+00
0.00E+00

Lair1
6
7
0.937
0.008
1.59E+00
0.00E+00
0.00E+00

Alox5ap
6
7
0.937
0.004
1.58E+00
0.00E+00
0.00E+00

Fcer1g
6
7
0.917
0.019
1.55E+00
0.00E+00
0.00E+00

Unc93b1
6
7
0.934
0.065
1.50E+00
0.00E+00
0.00E+00

Bcl11a
6
7
0.889
0.007
1.44E+00
0.00E+00
0.00E+00

Ncf1
6
7
0.861
0.019
1.43E+00
0.00E+00
0.00E+00

P2ry14
6
7
0.874
0.006
1.40E+00
0.00E+00
0.00E+00

Pltp
6
7
0.842
0.004
1.32E+00
0.00E+00
0.00E+00

Smim5
6
7
0.781
0.001
1.32E+00
0.00E+00
0.00E+00

Upb1
6
7
0.86
0.008
1.29E+00
0.00E+00
0.00E+00

Napsa
6
7
0.849
0.019
1.28E+00
0.00E+00
0.00E+00

Ppfia4
6
7
0.864
0.002
1.24E+00
0.00E+00
0.00E+00

Nucb2
6
7
0.868
0.043
1.22E+00
0.00E+00
0.00E+00

Spib
6
7
0.823
0.021
1.21E+00
0.00E+00
0.00E+00

Cadm1
6
7
0.848
0.001
1.18E+00
0.00E+00
0.00E+00

Cd68
6
7
0.83
0.01
1.17E+00
0.00E+00
0.00E+00

Runx2
6
7
0.811
0.023
1.17E+00
0.00E+00
0.00E+00

Pkib
6
7
0.782
0.004
1.15E+00
0.00E+00
0.00E+00

Kctd12
6
7
0.81
0.02
1.15E+00
0.00E+00
0.00E+00

Blnk
6
7
0.812
0.022
1.12E+00
0.00E+00
0.00E+00

Amica1
6
7
0.791
0.007
1.11E+00
0.00E+00
0.00E+00

Kmo
6
7
0.79
0.003
1.03E+00
0.00E+00
0.00E+00

Gapt
6
7
0.69
0.002
9.05E−01
0.00E+00
0.00E+00

Sh3bgr
6
7
0.7
0
9.59E−01
4.1E−312
7.41E−305

Pkig
6
7
0.839
0.041
1.13E+00
1.6E−311
2.85E−304

Scimp
6
7
0.785
0.019
1.06E+00
8.50E−308
1.51E−300

Fcrla
6
7
0.788
0.02
1.26E+00
8.04E−303
1.42E−295

Lefty1
6
7
0.739
0.01
9.87E−01
5.71E−302
1.01E−294

H2-DMb1
6
7
0.711
0.007
1.12E+00
1.26E−294
2.23E−287

Hpse
6
7
0.73
0.008
9.91E−01
1.52E−294
2.68E−287

Ccr2
6
7
0.777
0.046
1.17E+00
4.98E−290
8.82E−283

Zeb2
6
7
0.725
0.022
9.78E−01
2.15E−287
3.81E−280

Pir
6
7
0.67
0.001
1.01E+00
4.22E−276
7.48E−269

Atp2a1
6
7
0.654
0.002
8.16E−01
5.80E−275
1.03E−267

Klrd1
6
7
0.685
0.007
8.81E−01
8.69E−275
1.54E−267

Mzb1
6
7
0.81
0.056
1.35E+00
5.34E−273
9.45E−266

Ifi30
6
7
0.846
0.072
1.40E+00
3.49E−267
6.18E−260

Lgals3
6
7
0.756
0.03
1.16E+00
7.20E−261
1.27E−253

I830077J02Rik
6
7
0.63
0
8.08E−01
3.03E−260
5.36E−253

Cd209a
6
7
0.578
0
1.25E+00
4.68E−251
8.29E−244

Tubgcp5
6
7
0.744
0.04
9.82E−01
1.35E−243
2.39E−236

Cd209d
6
7
0.564
0.001
1.30E+00
1.68E−242
2.98E−235

Tbc1d8
6
7
0.593
0.002
7.06E−01
7.43E−239
1.32E−231

Plekhm3
6
7
0.635
0.013
7.47E−01
1.32E−238
2.33E−231

Cd180
6
7
0.627
0.012
7.71E−01
4.96E−238
8.78E−231

Lyn
6
7
0.681
0.017
8.20E−01
7.23E−237
1.28E−229

Abhd17b
6
7
0.78
0.076
1.07E+00
8.27E−237
1.46E−229

Slamf9
6
7
0.592
0.002
8.00E−01
9.18E−236
1.62E−228

Sdc4
6
7
0.676
0.041
8.52E−01
4.11E−234
7.28E−227

Klra17
6
7
0.57
0.001
7.70E−01
2.06E−231
3.65E−224

Csf2rb
6
7
0.577
0.001
6.97E−01
6.95E−228
1.23E−220

Plek
6
7
0.634
0.017
8.31E−01
7.06E−225
1.25E−217

Lifr
6
7
0.543
0
6.51E−01
1.41E−224
2.50E−217

Rell1
6
7
0.586
0.005
7.41E−01
3.01E−223
5.32E−216

Pgr
6
7
0.623
0.01
7.38E−01
1.35E−222
2.38E−215

Lat2
6
7
0.644
0.019
7.70E−01
3.62E−215
6.41E−208

Gsn
6
7
0.819
0.08
1.09E+00
5.35E−215
9.47E−208

Havcr1
6
7
0.568
0.005
6.33E−01
1.48E−214
2.62E−207

Spns3
6
7
0.564
0.002
6.76E−01
2.36E−213
4.17E−206

Hs3st1
6
7
0.551
0.006
7.40E−01
4.11E−201
7.28E−194

Lmo2
6
7
0.563
0.011
6.36E−01
6.60E−200
1.17E−192

Pafah1b3
6
7
0.776
0.086
9.60E−01
2.03E−195
3.60E−188

Rpgrip1
6
7
0.5
0.005
6.57E−01
2.36E−194
4.17E−187

Plaur
6
7
0.561
0.019
9.97E−01
1.31E−193
2.32E−186

Flt3
6
7
0.51
0.002
5.96E−01
3.20E−190
5.67E−183

Hhex
6
7
0.553
0.011
6.88E−01
2.52E−187
4.46E−180

Klrk1
6
7
0.522
0.009
6.98E−01
8.33E−183
1.47E−175

Nek6
6
7
0.518
0.005
6.07E−01
3.08E−179
5.45E−172

Mctp2
6
7
0.5
0.009
5.78E−01
1.98E−176
3.51E−169

Hmgn3
6
7
0.6
0.033
6.78E−01
2.45E−171
4.33E−164

Syk
6
7
0.5
0.01
5.68E−01
5.95E−168
1.05E−160

Tmem229b
6
7
0.706
0.071
8.24E−01
3.39E−167
6.00E−160

Gpr137b
6
7
0.53
0.019
5.62E−01
3.22E−165
5.70E−158

Irf5
6
7
0.61
0.038
6.73E−01
1.51E−164
2.68E−157

Irf7
6
7
0.712
0.076
1.06E+00
2.37E−163
4.19E−156

Trf
6
7
0.513
0.017
6.03E−01
1.96E−158
3.47E−151

Klk1
6
8
0.96
0.074
2.61E+00
0.00E+00
0.00E+00

Cox6a2
6
8
0.969
0.044
2.41E+00
0.00E+00
0.00E+00

Rnase6
6
8
0.992
0.035
2.33E+00
0.00E+00
0.00E+00

Iglc3
6
8
0.968
0.04
2.28E+00
0.00E+00
0.00E+00

Ctsh
6
8
0.988
0.087
2.22E+00
0.00E+00
0.00E+00

Ctsl
6
8
0.96
0.053
2.11E+00
0.00E+00
0.00E+00

Mpeg1
6
8
0.983
0.041
2.06E+00
0.00E+00
0.00E+00

Cybb
6
8
0.978
0.026
1.96E+00
0.00E+00
0.00E+00

D13Ertd608e
6
8
0.924
0.008
1.94E+00
0.00E+00
0.00E+00

Klk1b27
6
8
0.965
0.016
1.90E+00
0.00E+00
0.00E+00

Pld4
6
8
0.975
0.057
1.89E+00
0.00E+00
0.00E+00

Ccr9
6
8
0.956
0.051
1.88E+00
0.00E+00
0.00E+00

Clec12a
6
8
0.93
0.02
1.64E+00
0.00E+00
0.00E+00

Alox5ap
6
8
0.937
0.029
1.55E+00
0.00E+00
0.00E+00

Lair1
6
8
0.937
0.071
1.52E+00
0.00E+00
0.00E+00

Bcl11a
6
8
0.889
0.015
1.43E+00
0.00E+00
0.00E+00

Nucb2
6
8
0.868
0.01
1.25E+00
0.00E+00
0.00E+00

Ppfia4
6
8
0.864
0.014
1.23E+00
0.00E+00
0.00E+00

Upb1
6
8
0.86
0.016
1.28E+00
1.67E−306
2.96E−299

Cadm1
6
8
0.848
0.016
1.16E+00
2.18E−304
3.86E−297

Spib
6
8
0.823
0.017
1.21E+00
6.90E−290
1.22E−282

Smim5
6
8
0.781
0.01
1.31E+00
2.86E−281
5.07E−274

Gm2a
6
8
0.91
0.092
1.37E+00
2.30E−274
4.08E−267

Ifi27l2a
6
8
0.844
0.054
2.11E+00
4.32E−272
7.66E−265

P2ry14
6
8
0.874
0.058
1.34E+00
1.44E−261
2.55E−254

Cd68
6
8
0.83
0.022
1.16E+00
1.42E−258
2.51E−251

Blnk
6
8
0.812
0.02
1.12E+00
1.20E−256
2.13E−249

Mzb1
6
8
0.81
0.025
1.39E+00
2.40E−255
4.26E−248

Pkib
6
8
0.782
0.013
1.14E+00
1.14E−254
2.01E−247

Slpi
6
8
0.789
0.029
1.66E+00
1.77E−242
3.13E−235

Fcrla
6
8
0.788
0.015
1.27E+00
1.46E−237
2.58E−230

Pltp
6
8
0.842
0.043
1.28E+00
3.11E−233
5.52E−226

Pacsin1
6
8
0.819
0.03
1.08E+00
2.15E−232
3.81E−225

Lefty1
6
8
0.739
0.009
9.89E−01
5.65E−232
1.00E−224

Kmo
6
8
0.79
0.02
1.01E+00
5.62E−230
9.96E−223

Sh3bgr
6
8
0.7
0.005
9.54E−01
7.57E−224
1.34E−216

Ly86
6
8
0.733
0.014
9.74E−01
1.93E−218
3.42E−211

Gapt
6
8
0.69
0.023
8.82E−01
1.65E−215
2.92E−208

Ifi30
6
8
0.846
0.058
1.42E+00
1.18E−213
2.09E−206

Amica1
6
8
0.791
0.04
1.07E+00
3.89E−205
6.90E−198

Tnfrsf13b
6
8
0.786
0.037
1.02E+00
5.71E−204
1.01E−196

Bmyc
6
8
0.807
0.041
1.07E+00
9.53E−204
1.69E−196

H2-DMb1
6
8
0.711
0.018
1.11E+00
7.48E−201
1.32E−193

Trib1
6
8
0.722
0.027
1.05E+00
1.24E−197
2.20E−190

Gsn
6
8
0.819
0.038
1.14E+00
8.13E−194
1.44E−186

Atp2a1
6
8
0.654
0.01
8.08E−01
1.34E−189
2.38E−182

Pir
6
8
0.67
0.007
1.00E+00
5.75E−186
1.02E−178

Cd180
6
8
0.627
0.011
7.71E−01
1.18E−182
2.09E−175

Tubgcp5
6
8
0.744
0.046
9.75E−01
8.31E−181
1.47E−173

Cd200
6
8
0.609
0.007
7.81E−01
1.45E−172
2.57E−165

Slamf9
6
8
0.592
0.004
7.97E−01
3.45E−171
6.11E−164

Cd209d
6
8
0.564
0.011
1.29E+00
3.78E−166
6.69E−159

Hpse
6
8
0.73
0.041
9.58E−01
1.70E−165
3.00E−158

I830077J02Rik
6
8
0.63
0.012
7.96E−01
3.02E−162
5.34E−155

Havcr1
6
8
0.568
0.007
6.31E−01
2.53E−159
4.47E−152

Tbc1d8
6
8
0.593
0.011
6.96E−01
5.35E−159
9.47E−152

Tyrobp
6
9
0.999
0.093
3.64E+00
0.00E+00
0.00E+00

Ccl4
6
9
0.868
0.033
3.40E+00
0.00E+00
0.00E+00

Bst2
6
9
0.998
0.099
3.31E+00
0.00E+00
0.00E+00

Ly6c2
6
9
0.997
0.036
3.16E+00
0.00E+00
0.00E+00

Siglech
6
9
0.998
0.022
2.77E+00
0.00E+00
0.00E+00

Klk1
6
9
0.96
0.021
2.67E+00
0.00E+00
0.00E+00

Ly6c1
6
9
0.991
0.008
2.63E+00
0.00E+00
0.00E+00

Cox6a2
6
9
0.969
0.013
2.48E+00
0.00E+00
0.00E+00

Grn
6
9
0.986
0.1
2.19E+00
0.00E+00
0.00E+00

Ctsl
6
9
0.96
0.021
2.14E+00
0.00E+00
0.00E+00

Mpeg1
6
9
0.983
0.02
2.07E+00
0.00E+00
0.00E+00

Cd7
6
9
0.954
0.077
1.94E+00
0.00E+00
0.00E+00

D13Ertd608e
6
9
0.924
0.002
1.94E+00
0.00E+00
0.00E+00

Klk1b27
6
9
0.965
0.008
1.91E+00
0.00E+00
0.00E+00

Ccr9
6
9
0.956
0.017
1.91E+00
0.00E+00
0.00E+00

Sell
6
9
0.973
0.062
1.82E+00
0.00E+00
0.00E+00

Cd8b1
6
9
0.593
0.057
1.75E+00
0.00E+00
0.00E+00

Tsc22d1
6
9
0.908
0.021
1.66E+00
0.00E+00
0.00E+00

Lair1
6
9
0.937
0.008
1.59E+00
0.00E+00
0.00E+00

S100a6
6
9
0.895
0.029
1.58E+00
0.00E+00
0.00E+00

Alox5ap
6
9
0.937
0.005
1.58E+00
0.00E+00
0.00E+00

Fcer1g
6
9
0.917
0.038
1.52E+00
0.00E+00
0.00E+00

Atp1b1
6
9
0.897
0.016
1.50E+00
0.00E+00
0.00E+00

Gpr171
6
9
0.847
0.081
1.47E+00
0.00E+00
0.00E+00

Rilpl2
6
9
0.857
0.078
1.45E+00
0.00E+00
0.00E+00

P2ry14
6
9
0.874
0.008
1.40E+00
0.00E+00
0.00E+00

Smim5
6
9
0.781
0.003
1.32E+00
0.00E+00
0.00E+00

Pltp
6
9
0.842
0.015
1.31E+00
0.00E+00
0.00E+00

Cd209d
6
9
0.564
0.005
1.29E+00
0.00E+00
0.00E+00

Ramp1
6
9
0.879
0.053
1.29E+00
0.00E+00
0.00E+00

Upb1
6
9
0.86
0.005
1.29E+00
0.00E+00
0.00E+00

Ccr2
6
9
0.777
0.004
1.26E+00
0.00E+00
0.00E+00

Cd209a
6
9
0.578
0.004
1.25E+00
0.00E+00
0.00E+00

Ifnar2
6
9
0.868
0.023
1.24E+00
0.00E+00
0.00E+00

Ppfia4
6
9
0.864
0.005
1.24E+00
0.00E+00
0.00E+00

Nucb2
6
9
0.868
0.046
1.21E+00
0.00E+00
0.00E+00

Runx2
6
9
0.811
0.009
1.19E+00
0.00E+00
0.00E+00

Cadm1
6
9
0.848
0.003
1.18E+00
0.00E+00
0.00E+00

Lgals3
6
9
0.756
0.035
1.15E+00
0.00E+00
0.00E+00

Kctd12
6
9
0.81
0.017
1.15E+00
0.00E+00
0.00E+00

Cd68
6
9
0.83
0.042
1.14E+00
0.00E+00
0.00E+00

Amica1
6
9
0.791
0.009
1.11E+00
0.00E+00
0.00E+00

Snx18
6
9
0.81
0.075
1.08E+00
0.00E+00
0.00E+00

Plaur
6
9
0.561
0.009
1.01E+00
0.00E+00
0.00E+00

Pir
6
9
0.67
0.003
1.00E+00
0.00E+00
0.00E+00

Trib1
6
9
0.722
0.072
1.00E+00
0.00E+00
0.00E+00

Il7r
6
9
0.757
0.043
9.84E−01
0.00E+00
0.00E+00

Zeb2
6
9
0.725
0.02
9.80E−01
0.00E+00
0.00E+00

Sh3bgr
6
9
0.7
0.005
9.53E−01
0.00E+00
0.00E+00

Socs3
6
9
0.52
0.033
9.25E−01
0.00E+00
0.00E+00

Mndal
6
9
0.694
0.035
9.07E−01
0.00E+00
0.00E+00

Ahnak
6
9
0.688
0.022
8.99E−01
0.00E+00
0.00E+00

Klrd1
6
9
0.685
0.015
8.78E−01
0.00E+00
0.00E+00

Timp2
6
9
0.68
0.019
8.59E−01
0.00E+00
0.00E+00

Gapt
6
9
0.69
0.048
8.58E−01
0.00E+00
0.00E+00

Sdc4
6
9
0.676
0.038
8.50E−01
0.00E+00
0.00E+00

Gpr183
6
9
0.624
0.07
8.40E−01
0.00E+00
0.00E+00

Sla2
6
9
0.67
0.026
8.33E−01
0.00E+00
0.00E+00

Irf2bp2
6
9
0.712
0.101
8.18E−01
0.00E+00
0.00E+00

Atp2a1
6
9
0.654
0.002
8.16E−01
0.00E+00
0.00E+00

I830077J02Rik
6
9
0.63
0.004
8.03E−01
0.00E+00
0.00E+00

Slamf9
6
9
0.592
0.003
7.98E−01
0.00E+00
0.00E+00

Irf1
6
9
0.65
0.092
7.96E−01
0.00E+00
0.00E+00

Tmem229b
6
9
0.706
0.1
7.91E−01
0.00E+00
0.00E+00

Rnf149
6
9
0.601
0.075
7.79E−01
0.00E+00
0.00E+00

Klra17
6
9
0.57
0.003
7.68E−01
0.00E+00
0.00E+00

Zyx
6
9
0.623
0.036
7.62E−01
0.00E+00
0.00E+00

Adgre5
6
9
0.617
0.052
7.57E−01
0.00E+00
0.00E+00

Ifi203
6
9
0.573
0.048
7.44E−01
0.00E+00
0.00E+00

Rell1
6
9
0.586
0.021
7.24E−01
0.00E+00
0.00E+00

Klrk1
6
9
0.522
0.005
7.05E−01
0.00E+00
0.00E+00

Tbc1d8
6
9
0.593
0.003
7.04E−01
0.00E+00
0.00E+00

Lag3
6
9
0.548
0.016
7.01E−01
0.00E+00
0.00E+00

Itgb7
6
9
0.622
0.075
7.00E−01
0.00E+00
0.00E+00

Csf2rb
6
9
0.577
0.006
6.92E−01
0.00E+00
0.00E+00

Trim30a
6
9
0.597
0.067
6.84E−01
0.00E+00
0.00E+00

Plekhm3
6
9
0.635
0.074
6.76E−01
0.00E+00
0.00E+00

Spns3
6
9
0.564
0.009
6.69E−01
0.00E+00
0.00E+00

Fgr
6
9
0.623
0.081
6.65E−01
0.00E+00
0.00E+00

Lifr
6
9
0.543
0.006
6.45E−01
0.00E+00
0.00E+00

Il10rb
6
9
0.59
0.045
6.29E−01
0.00E+00
0.00E+00

Trf
6
9
0.513
0.005
6.19E−01
0.00E+00
0.00E+00

Tex2
6
9
0.522
0.012
5.68E−01
0.00E+00
0.00E+00

Runx3
6
9
0.567
0.097
6.09E−01
1.44E−305
2.54E−298

Cmah
6
9
0.546
0.077
5.36E−01
8.39E−296
1.48E−288

Mctp2
6
9
0.5
0.038
5.49E−01
1.53E−293
2.71E−286

Nek6
6
9
0.518
0.089
5.18E−01
3.80E−284
6.73E−277

Rnf122
6
9
0.525
0.058
5.87E−01
1.18E−279
2.08E−272

Rpgrip1
6
9
0.5
0.039
6.19E−01
8.44E−279
1.50E−271

Bhlhe40
6
9
0.504
0.05
6.30E−01
2.55E−276
4.51E−269

Tyrobp
6
10
0.999
0.064
3.65E+00
0.00E+00
0.00E+00

Ccl4
6
10
0.868
0.025
3.41E+00
0.00E+00
0.00E+00

Plac8
6
10
0.999
0.063
3.39E+00
0.00E+00
0.00E+00

Bst2
6
10
0.998
0.051
3.36E+00
0.00E+00
0.00E+00

Ly6c2
6
10
0.997
0.019
3.17E+00
0.00E+00
0.00E+00

Siglech
6
10
0.998
0.011
2.78E+00
0.00E+00
0.00E+00

Klk1
6
10
0.96
0.014
2.67E+00
0.00E+00
0.00E+00

Ly6c1
6
10
0.991
0.007
2.62E+00
0.00E+00
0.00E+00

Cox6a2
6
10
0.969
0.008
2.48E+00
0.00E+00
0.00E+00

Grn
6
10
0.986
0.044
2.26E+00
0.00E+00
0.00E+00

Ctsl
6
10
0.96
0.016
2.14E+00
0.00E+00
0.00E+00

Mpeg1
6
10
0.983
0.015
2.08E+00
0.00E+00
0.00E+00

Cd7
6
10
0.954
0.043
1.97E+00
0.00E+00
0.00E+00

D13Ertd608e
6
10
0.924
0.001
1.94E+00
0.00E+00
0.00E+00

Ccr9
6
10
0.956
0.008
1.93E+00
0.00E+00
0.00E+00

Selplg
6
10
0.983
0.09
1.92E+00
0.00E+00
0.00E+00

Klk1b27
6
10
0.965
0.005
1.92E+00
0.00E+00
0.00E+00

Sell
6
10
0.973
0.042
1.84E+00
0.00E+00
0.00E+00

Tsc22d1
6
10
0.908
0.015
1.67E+00
0.00E+00
0.00E+00

S100a6
6
10
0.895
0.01
1.61E+00
0.00E+00
0.00E+00

Lair1
6
10
0.937
0.004
1.59E+00
0.00E+00
0.00E+00

Alox5ap
6
10
0.937
0.005
1.58E+00
0.00E+00
0.00E+00

Fyb
6
10
0.944
0.059
1.52E+00
0.00E+00
0.00E+00

Fcer1g
6
10
0.917
0.032
1.52E+00
0.00E+00
0.00E+00

Atp1b1
6
10
0.897
0.009
1.51E+00
0.00E+00
0.00E+00

Rilpl2
6
10
0.857
0.049
1.49E+00
0.00E+00
0.00E+00

Gpr171
6
10
0.847
0.076
1.48E+00
0.00E+00
0.00E+00

Emp3
6
10
0.897
0.071
1.43E+00
0.00E+00
0.00E+00

P2ry14
6
10
0.874
0.005
1.40E+00
0.00E+00
0.00E+00

Ramp1
6
10
0.879
0.019
1.33E+00
0.00E+00
0.00E+00

Smim5
6
10
0.781
0.001
1.32E+00
0.00E+00
0.00E+00

Pltp
6
10
0.842
0.012
1.31E+00
0.00E+00
0.00E+00

Upb1
6
10
0.86
0.001
1.29E+00
0.00E+00
0.00E+00

Ccr2
6
10
0.777
0.002
1.26E+00
0.00E+00
0.00E+00

Ifnar2
6
10
0.868
0.015
1.25E+00
0.00E+00
0.00E+00

Ppfia4
6
10
0.864
0.006
1.24E+00
0.00E+00
0.00E+00

Nucb2
6
10
0.868
0.034
1.23E+00
0.00E+00
0.00E+00

S100a11
6
10
0.877
0.09
1.22E+00
0.00E+00
0.00E+00

Runx2
6
10
0.811
0.005
1.19E+00
0.00E+00
0.00E+00

Cadm1
6
10
0.848
0.001
1.18E+00
0.00E+00
0.00E+00

Lgals3
6
10
0.756
0.03
1.17E+00
0.00E+00
0.00E+00

Cd68
6
10
0.83
0.019
1.17E+00
0.00E+00
0.00E+00

Kctd12
6
10
0.81
0.017
1.15E+00
0.00E+00
0.00E+00

Snx18
6
10
0.81
0.046
1.11E+00
0.00E+00
0.00E+00

Amica1
6
10
0.791
0.009
1.11E+00
0.00E+00
0.00E+00

Evi2a
6
10
0.768
0.076
1.05E+00
0.00E+00
0.00E+00

Trib1
6
10
0.722
0.046
1.03E+00
0.00E+00
0.00E+00

Pir
6
10
0.67
0.002
1.01E+00
0.00E+00
0.00E+00

Il7r
6
10
0.757
0.026
1.00E+00
0.00E+00
0.00E+00

Zeb2
6
10
0.725
0.015
9.84E−01
0.00E+00
0.00E+00

Tubgcp5
6
10
0.744
0.051
9.72E−01
0.00E+00
0.00E+00

Sh3bgr
6
10
0.7
0.004
9.55E−01
0.00E+00
0.00E+00

Kmo
6
10
0.79
0.075
9.52E−01
0.00E+00
0.00E+00

Litaf
6
10
0.728
0.049
9.47E−01
0.00E+00
0.00E+00

Mndal
6
10
0.694
0.024
9.27E−01
0.00E+00
0.00E+00

Ahnak
6
10
0.688
0.018
9.02E−01
0.00E+00
0.00E+00

Klrd1
6
10
0.685
0.007
8.85E−01
0.00E+00
0.00E+00

Timp2
6
10
0.68
0.014
8.66E−01
0.00E+00
0.00E+00

Sla2
6
10
0.67
0.016
8.43E−01
0.00E+00
0.00E+00

Atp2a1
6
10
0.654
0.001
8.17E−01
0.00E+00
0.00E+00

I830077J02Rik
6
10
0.63
0.002
8.07E−01
0.00E+00
0.00E+00

Tbc1d8
6
10
0.593
0.001
7.06E−01
3.7E−313
6.72E−306

Cd209a
6
10
0.578
0.002
1.25E+00
5.29E−306
9.37E−299

Slamf9
6
10
0.592
0.004
7.98E−01
7.25E−302
1.28E−294

Sdc4
6
10
0.676
0.044
8.31E−01
3.09E−300
5.47E−293

Klra17
6
10
0.57
0.001
7.71E−01
6.75E−298
1.20E−290

Tmem229b
6
10
0.706
0.059
8.33E−01
1.66E−295
2.94E−288

Cd209d
6
10
0.564
0.006
1.29E+00
1.24E−287
2.20E−280

Csf2rb
6
10
0.577
0.005
6.92E−01
4.51E−283
7.98E−276

Plaur
6
10
0.561
0.006
1.01E+00
5.25E−282
9.31E−275

Rell1
6
10
0.586
0.01
7.35E−01
6.41E−281
1.14E−273

Irf2bp2
6
10
0.712
0.073
8.55E−01
4.60E−278
8.14E−271

Zyx
6
10
0.623
0.024
7.76E−01
6.37E−273
1.13E−265

Cd8b1
6
10
0.593
0.027
1.78E+00
9.61E−270
1.70E−262

Lifr
6
10
0.543
0.005
6.46E−01
2.42E−266
4.28E−259

Tex2
6
10
0.522
0.002
5.78E−01
1.30E−261
2.30E−254

Adgre5
6
10
0.617
0.03
7.77E−01
3.51E−260
6.22E−253

Lag3
6
10
0.548
0.007
7.10E−01
1.09E−255
1.93E−248

Spns3
6
10
0.564
0.011
6.66E−01
2.50E−254
4.43E−247

Ifi203
6
10
0.573
0.023
7.73E−01
9.81E−254
1.74E−246

Klrk1
6
10
0.522
0.005
7.03E−01
1.72E−251
3.05E−244

Irf7
6
10
0.712
0.1
1.04E+00
5.55E−251
9.83E−244

Il10rb
6
10
0.59
0.026
6.48E−01
2.77E−249
4.90E−242

Leprotl1
6
10
0.634
0.045
6.91E−01
8.56E−245
1.52E−237

Trf
6
10
0.513
0.006
6.20E−01
1.30E−239
2.30E−232

Irf1
6
10
0.65
0.065
8.30E−01
3.67E−239
6.51E−232

Rnf149
6
10
0.601
0.041
8.20E−01
3.18E−228
5.63E−221

Trim30a
6
10
0.597
0.045
7.07E−01
1.57E−226
2.78E−219

Fgr
6
10
0.623
0.055
6.93E−01
1.46E−225
2.59E−218

Gpr183
6
10
0.624
0.048
8.64E−01
1.35E−223
2.38E−216

Itgb7
6
10
0.622
0.058
7.28E−01
3.41E−217
6.04E−210

Socs3
6
10
0.52
0.019
9.44E−01
2.02E−212
3.58E−205

Mctp2
6
10
0.5
0.02
5.67E−01
6.79E−202
1.20E−194

Runx3
6
10
0.567
0.049
6.86E−01
2.44E−196
4.33E−189

Cmah
6
10
0.546
0.038
5.94E−01
3.91E−195
6.93E−188

Plekhm3
6
10
0.635
0.097
6.60E−01
3.70E−191
6.55E−184

Hhex
6
10
0.553
0.048
6.41E−01
3.86E−186
6.83E−179

Rnf13
6
10
0.633
0.101
6.50E−01
2.27E−184
4.02E−177

Cd44
6
10
0.609
0.085
6.75E−01
3.87E−179
6.84E−172

Nek6
6
10
0.518
0.037
5.74E−01
1.56E−174
2.77E−167

Man1a2
6
10
0.548
0.063
5.81E−01
6.02E−172
1.06E−164

Gpr137b
6
10
0.53
0.053
5.28E−01
3.43E−170
6.07E−163

Bhlhe40
6
10
0.504
0.04
6.37E−01
3.39E−163
6.00E−156

Rnf122
6
10
0.525
0.064
5.80E−01
3.97E−159
7.02E−152

Ly6c2
6
11
0.997
0.069
3.10E+00
0.00E+00
0.00E+00

Siglech
6
11
0.998
0.093
2.69E+00
0.00E+00
0.00E+00

Ly6c1
6
11
0.991
0.028
2.59E+00
0.00E+00
0.00E+00

Cox6a2
6
11
0.969
0.037
2.45E+00
0.00E+00
0.00E+00

Iglc3
6
11
0.968
0.024
2.38E+00
0.00E+00
0.00E+00

Rnase6
6
11
0.992
0.031
2.33E+00
0.00E+00
0.00E+00

Ctsh
6
11
0.988
0.07
2.23E+00
0.00E+00
0.00E+00

Mpeg1
6
11
0.983
0.048
2.05E+00
0.00E+00
0.00E+00

Cybb
6
11
0.978
0.028
1.95E+00
0.00E+00
0.00E+00

Klk1b27
6
11
0.965
0.011
1.91E+00
5.08E−307
9.00E−300

Pld4
6
11
0.975
0.053
1.90E+00
4.35E−294
7.70E−287

Klk1
6
11
0.96
0.066
2.62E+00
6.06E−290
1.07E−282

Ctsl
6
11
0.96
0.046
2.11E+00
5.69E−268
1.01E−260

Sell
6
11
0.973
0.094
1.77E+00
1.66E−265
2.95E−258

Lair1
6
11
0.937
0.021
1.57E+00
1.26E−262
2.23E−255

Mef2c
6
11
0.947
0.048
1.59E+00
1.86E−250
3.30E−243

Clec12a
6
11
0.93
0.025
1.63E+00
1.14E−244
2.02E−237

D13Ertd608e
6
11
0.924
0.007
1.94E+00
7.09E−243
1.26E−235

Alox5ap
6
11
0.937
0.031
1.55E+00
9.83E−238
1.74E−230

Bcl11a
6
11
0.889
0.018
1.43E+00
5.00E−214
8.85E−207

Ppfia4
6
11
0.864
0.014
1.23E+00
3.73E−208
6.60E−201

Tsc22d1
6
11
0.908
0.075
1.60E+00
2.65E−201
4.69E−194

Nucb2
6
11
0.868
0.01
1.25E+00
1.19E−199
2.11E−192

P2ry14
6
11
0.874
0.024
1.38E+00
2.54E−193
4.50E−186

Cadm1
6
11
0.848
0.012
1.17E+00
3.48E−192
6.15E−185

Upb1
6
11
0.86
0.015
1.28E+00
4.89E−185
8.66E−178

Ifi27l2a
6
11
0.844
0.07
2.10E+00
6.88E−179
1.22E−171

Spib
6
11
0.823
0.022
1.21E+00
7.33E−177
1.30E−169

Smim5
6
11
0.781
0.012
1.31E+00
2.16E−174
3.82E−167

Cd68
6
11
0.83
0.016
1.17E+00
5.67E−160
l.OOE−152

Slpi
6
11
0.789
0.024
1.67E+00
4.23E−159
7.48E−152

Ly6c2
6
12
0.997
0.048
3.15E+00
0.00E+00
0.00E+00

Ly6c1
6
12
0.991
0.017
2.61E+00
0.00E+00
0.00E+00

Cox6a2
6
12
0.969
0.027
2.46E+00
0.00E+00
0.00E+00

Iglc3
6
12
0.968
0.019
2.38E+00
0.00E+00
0.00E+00

Rnase6
6
12
0.992
0.032
2.33E+00
0.00E+00
0.00E+00

Ctsh
6
12
0.988
0.098
2.20E+00
0.00E+00
0.00E+00

Mpeg1
6
12
0.983
0.036
2.06E+00
0.00E+00
0.00E+00

Klk1b27
6
12
0.965
0.018
1.90E+00
5.0E−315
8.89E−308

Pld4
6
12
0.975
0.061
1.90E+00
1.48E−307
2.62E−300

Tcf4
6
12
0.977
0.096
1.84E+00
1.50E−304
2.65E−297

Klk1
6
12
0.96
0.072
2.61E+00
4.78E−300
8.46E−293

Lgals1
6
12
0.978
0.085
2.13E+00
7.50E−297
1.33E−289

Sell
6
12
0.973
0.081
1.79E+00
9.66E−291
1.71E−283

Mef2c
6
12
0.947
0.021
1.62E+00
1.14E−287
2.02E−280

Lair1
6
12
0.937
0.023
1.57E+00
2.43E−274
4.30E−267

Ctsl
6
12
0.96
0.067
2.09E+00
5.61E−273
9.93E−266

Clec12a
6
12
0.93
0.017
1.64E+00
2.53E−265
4.47E−258

D13Ertd608e
6
12
0.924
0.007
1.94E+00
5.62E−257
9.96E−250

Alox5ap
6
12
0.937
0.032
1.55E+00
1.67E−253
2.95E−246

Ctss
6
12
0.96
0.087
1.71E+00
1.39E−238
2.46E−231

Bcl11a
6
12
0.889
0.023
1.43E+00
1.66E−217
2.95E−210

Atp1b1
6
12
0.897
0.033
1.48E+00
8.29E−213
1.47E−205

Ppfia4
6
12
0.864
0.017
1.23E+00
3.85E−212
6.82E−205

Cadm1
6
12
0.848
0.011
1.17E+00
3.92E−202
6.93E−195

Ifi27l2a
6
12
0.844
0.05
2.14E+00
5.33E−199
9.43E−192

Tsc22d1
6
12
0.908
0.099
1.55E+00
7.63E−195
1.35E−187

Nucb2
6
12
0.868
0.024
1.24E+00
2.42E−192
4.29E−185

Spib
6
12
0.823
0.021
1.21E+00
5.83E−184
1.03E−176

Upb1
6
12
0.86
0.026
1.27E+00
4.32E−182
7.65E−175

Ly6e
6
12
0.891
0.088
1.85E+00
9.81E−178
1.74E−170

Smim5
6
12
0.781
0.018
1.30E+00
5.63E−173
9.97E−166

Slpi
6
12
0.789
0.024
1.67E+00
4.60E−164
8.15E−157

Ncf1
6
12
0.861
0.072
1.38E+00
1.18E−163
2.08E−156

Cd68
6
12
0.83
0.024
1.16E+00
1.24E−160
2.19E−153

Scimp
6
12
0.785
0.008
1.07E+00
3.82E−159
6.75E−152

Pkib
6
12
0.782
0.019
1.14E+00
4.90E−158
8.67E−151

Ly6c2
6
14
0.997
0.094
3.04E+00
0.00E+00
0.00E+00

Ly6c1
6
14
0.991
0.041
2.56E+00
0.00E+00
0.00E+00

Cox6a2
6
14
0.969
0.049
2.44E+00
0.00E+00
0.00E+00

Iglc3
6
14
0.968
0.092
2.23E+00
0.00E+00
0.00E+00

D13Ertd608e
6
14
0.924
0.014
1.93E+00
0.00E+00
0.00E+00

P2ry14
6
14
0.874
0.059
1.34E+00
0.00E+00
0.00E+00

Nucb2
6
14
0.868
0.08
1.17E+00
0.00E+00
0.00E+00

Mzb1
6
14
0.81
0.094
1.23E+00
2.0E−316
0.00E+00

Slpi
6
14
0.789
0.056
1.63E+00
3.1E−316
0.00E+00

Lefty1
6
14
0.739
0.033
9.62E−01
2.90E−292
5.14E−285

Ccr2
6
14
0.777
0.055
1.15E+00
8.71E−281
1.54E−273

Sh3bgr
6
14
0.7
0.022
9.38E−01
6.49E−278
1.15E−270

Pir
6
14
0.67
0.02
9.80E−01
3.81E−261
6.75E−254

Atp2a1
6
14
0.654
0.019
7.98E−01
9.82E−251
1.74E−243

Tubgcp5
6
14
0.744
0.095
9.24E−01
2.08E−249
3.69E−242

Hpse
6
14
0.73
0.099
8.88E−01
7.92E−242
1.40E−234

Timp2
6
14
0.68
0.049
8.30E−01
3.17E−239
5.61E−232

Havcr1
6
14
0.568
0.009
6.29E−01
2.65E−209
4.68E−202

Ctse
6
14
0.673
0.091
7.43E−01
1.66E−203
2.94E−196

Klra17
6
14
0.57
0.013
7.54E−01
4.42E−203
7.83E−196

Sla2
6
14
0.67
0.085
7.65E−01
1.99E−198
3.53E−191

Slamf9
6
14
0.592
0.05
7.44E−01
1.63E−188
2.89E−181

Cd209d
6
14
0.564
0.02
1.28E+00
3.15E−188
5.57E−181

Cd8b1
6
14
0.593
0.061
1.73E+00
2.83E−181
5.01E−174

Lifr
6
14
0.543
0.025
6.26E−01
3.74E−175
6.63E−168

Cmah
6
14
0.546
0.033
6.01E−01
6.25E−171
1.11E−163

Plac8
6
15
0.999
0.101
3.39E+00
1.33E−188
2.35E−181

Siglech
6
17
0.998
0.053
2.74E+00
0.00E+00
0.00E+00

Ly6c2
6
17
0.997
0.038
3.13E+00
7.09E−290
1.25E−282

Rnase6
6
17
0.992
0.032
2.33E+00
1.18E−267
2.10E−260

Ly6c1
6
17
0.991
0.009
2.61E+00
2.52E−265
4.47E−258

Ctsh
6
17
0.988
0.044
2.26E+00
9.57E−255
1.69E−247

Mpeg1
6
17
0.983
0.018
2.08E+00
1.59E−245
2.81E−238

Cybb
6
17
0.978
0.023
1.95E+00
1.45E−229
2.57E−222

Cox6a2
6
17
0.969
0.015
2.47E+00
8.65E−223
1.53E−215

Lgals1
6
17
0.978
0.065
2.24E+00
1.20E−213
2.12E−206

Iglc3
6
17
0.968
0.035
2.36E+00
1.61E−211
2.85E−204

Pld4
6
17
0.975
0.038
1.92E+00
3.79E−211
6.71E−204

Klk1b27
6
17
0.965
0.015
1.90E+00
1.19E−204
2.10E−197

Sell
6
17
0.973
0.062
1.80E+00
1.53E−198
2.70E−191

Klk1
6
17
0.96
0.059
2.63E+00
4.21E−192
7.45E−185

Ctsl
6
17
0.96
0.032
2.13E+00
2.12E−188
3.74E−181

Clec12a
6
17
0.93
0
1.66E+00
3.48E−180
6.16E−173

Alox5ap
6
17
0.937
0.006
1.58E+00
3.24E−177
5.73E−170

Mef2c
6
17
0.947
0.041
1.59E+00
9.11E−172
1.61E−164

Lair1
6
17
0.937
0.026
1.57E+00
6.35E−171
1.12E−163

D13Ertd608e
6
17
0.924
0.003
1.94E+00
1.23E−163
2.17E−156

Tyrobp
6
18
0.999
0.06
3.68E+00
0.00E+00
0.00E+00

Plac8
6
18
0.999
0.06
3.43E+00
0.00E+00
0.00E+00

Siglech
6
18
0.998
0.011
2.78E+00
1.41E−259
2.49E−252

Ly6c2
6
18
0.997
0.064
3.07E+00
1.48E−245
2.62E−238

Rnase6
6
18
0.992
0.007
2.36E+00
1.88E−233
3.34E−226

Ctsh
6
18
0.988
0.021
2.29E+00
1.17E−220
2.07E−213

Ly6c1
6
18
0.991
0.039
2.56E+00
1.84E−214
3.25E−207

Mpeg1
6
18
0.983
0.007
2.09E+00
2.41E−212
4.26E−205

Grn
6
18
0.986
0.046
2.27E+00
8.35E−202
1.48E−194

Tcf4
6
18
0.977
0.011
1.93E+00
1.24E−196
2.20E−189

Cybb
6
18
0.978
0.025
1.96E+00
2.11E−192
3.73E−185

Pld4
6
18
0.975
0.004
1.95E+00
1.18E−191
2.10E−184

Cox6a2
6
18
0.969
0.004
2.49E+00
4.26E−191
7.54E−184

Klk1b27
6
18
0.965
0.004
1.92E+00
6.06E−177
1.07E−169

Iglc3
6
18
0.968
0.053
2.35E+00
2.30E−174
4.08E−167

Klk1
6
18
0.96
0.018
2.67E+00
7.26E−171
1.29E−163

Siglech
6
19
0.998
0.048
2.74E+00
6.67E−163
1.18E−155

Mpeg1
6
20
0.983
0.076
2.01E+00
2.84E−257
5.03E−250

Cox6a2
6
20
0.969
0.068
2.42E+00
7.10E−237
1.26E−229

Klk1b27
6
20
0.965
0.059
1.86E+00
2.63E−218
4.66E−211

D13Ertd608e
6
20
0.924
0.013
1.93E+00
1.81E−197
3.21E−190

Lair1
6
20
0.937
0.034
1.56E+00
2.85E−195
5.05E−188

Alox5ap
6
20
0.937
0.068
1.50E+00
5.83E−181
1.03E−173

Clec12a
6
20
0.93
0.064
1.59E+00
2.00E−178
3.54E−171

Fyb
6
20
0.944
0.097
1.45E+00
1.49E−171
2.64E−164

Cox6a2
6
21
0.969
0.064
2.41E+00
1.26E−286
2.23E−279

Iglc3
6
21
0.968
0.081
2.31E+00
1.72E−274
3.05E−267

D13Ertd608e
6
21
0.924
0.021
1.92E+00
3.39E−254
6.01E−247

Atp1b1
6
21
0.897
0.081
1.42E+00
2.06E−204
3.64E−197

Pltp
6
21
0.842
0.094
1.17E+00
5.48E−176
9.70E−169

Pacsin1
6
21
0.819
0.06
1.04E+00
5.47E−173
9.69E−166

Cox6a2
6
22
0.969
0.039
2.45E+00
1.15E−237
2.04E−230

Klk1b27
6
22
0.965
0.017
1.90E+00
2.03E−237
3.59E−230

Iglc3
6
22
0.968
0.069
2.30E+00
2.07E−228
3.67E−221

Ccr9
6
22
0.956
0.06
1.86E+00
7.64E−206
1.35E−198

D13Ertd608e
6
22
0.924
0.004
1.94E+00
1.52E−198
2.70E−191

Siglech
6
24
0.998
0.085
2.66E+00
0.00E+00
0.00E+00

Ly6c2
6
24
0.997
0.072
2.99E+00
2.84E−299
5.03E−292

Ly6c1
6
24
0.991
0.013
2.57E+00
1.26E−280
2.23E−273

Mpeg1
6
24
0.983
0.067
1.94E+00
4.29E−240
7.60E−233

Cox6a2
6
24
0.969
0.031
2.42E+00
7.94E−234
1.41E−226

Sell
6
24
0.973
0.063
1.80E+00
2.73E−224
4.84E−217

Iglc3
6
24
0.968
0.081
2.27E+00
2.72E−220
4.81E−213

Klk1b27
6
24
0.965
0.054
1.86E+00
3.66E−216
6.49E−209

D13Ertd608e
6
24
0.924
0.004
1.93E+00
1.09E−194
1.93E−187

Clec12a
6
24
0.93
0.036
1.57E+00
5.33E−180
9.44E−173

Rnase6
6
25
0.992
0.023
2.34E+00
6.71E−176
1.19E−168

Ighm
6
25
0.993
0.077
2.22E+00
4.96E−173
8.78E−166

Ly6c2
6
26
0.997
0.074
3.02E+00
1.89E−279
3.35E−272

Ly6c1
6
26
0.991
0.014
2.58E+00
1.16E−259
2.05E−252

Mpeg1
6
26
0.983
0.065
2.01E+00
7.29E−228
1.29E−220

Cybb
6
26
0.978
0.055
1.89E+00
5.08E−215
8.99E−208

Pld4
6
26
0.975
0.083
1.84E+00
3.94E−209
6.97E−202

Cox6a2
6
26
0.969
0.055
2.38E+00
6.24E−207
1.10E−199

Tcf4
6
26
0.977
0.097
1.81E+00
1.15E−206
2.03E−199

Iglc3
6
26
0.968
0.069
2.29E+00
1.39E−204
2.45E−197

Klk1b27
6
26
0.965
0.065
1.83E+00
3.67E−190
6.49E−183

Ctss
6
26
0.96
0.088
1.68E+00
2.68E−184
4.75E−177

Mef2c
6
26
0.947
0.037
1.59E+00
2.52E−178
4.46E−171

Ccr9
6
26
0.956
0.065
1.83E+00
1.24E−177
2.19E−170

D13Ertd608e
6
26
0.924
0.014
1.90E+00
2.13E−166
3.77E−159

Clec12a
6
26
0.93
0.046
1.60E+00
9.21E−160
1.63E−152

Siglech
6
29
0.998
0.014
2.74E+00
9.57E−222
1.69E−214

Ly6c2
6
29
0.997
0.101
2.92E+00
1.64E−203
2.90E−196

Grn
6
29
0.986
0.095
2.18E+00
5.73E−184
1.02E−176

Ly6c1
6
29
0.991
0.074
2.45E+00
2.29E−183
4.05E−176

Mpeg1
6
29
0.983
0.047
2.03E+00
4.62E−183
8.17E−176

Cox6a2
6
29
0.969
0.014
2.48E+00
8.33E−165
1.47E−157

Klk1b27
6
29
0.965
0.014
1.91E+00
2.04E−160
3.61E−153

Siglech
6
30
0.998
0.067
2.69E+00
2.05E−162
3.62E−155

Siglech
6
33
0.998
0.076
2.68E+00
6.01E−198
1.06E−190

Ly6c2
6
33
0.997
0.019
3.18E+00
4.19E−173
7.41E−166

Rnase6
6
35
0.992
0.071
2.24E+00
4.20E−180
7.44E−173

Ly6c1
6
35
0.991
0.02
2.53E+00
6.21E−175
1.10E−167

Pld4
6
35
0.975
0.101
1.80E+00
1.27E−163
2.24E−156

Siglech
6
37
0.998
0.034
2.76E+00
1.07E−186
1.89E−179

Ctsh
6
37
0.988
0.057
2.25E+00
7.37E−162
1.30E−154

Ly6c2
6
37
0.997
0.08
2.93E+00
1.15E−160
2.03E−153

Grn
6
37
0.986
0.068
2.21E+00
4.72E−159
8.35E−152

Rnase6
6
37
0.992
0.023
2.34E+00
8.48E−159
1.50E−151

Izumo1r
7
8
0.861
0.008
1.63E+00
0.00E+00
0.00E+00

Ifi27l2a
7
8
0.802
0.054
1.61E+00
0.00E+00
0.00E+00

Cd3e
7
8
0.94
0.016
1.59E+00
0.00E+00
0.00E+00

Trac
7
8
0.883
0.056
1.47E+00
0.00E+00
0.00E+00

Rgs10
7
8
0.857
0.099
1.46E+00
0.00E+00
0.00E+00

Izumo1r
7
9
0.861
0.062
1.57E+00
0.00E+00
0.00E+00

Trac
7
9
0.883
0.083
1.45E+00
0.00E+00
0.00E+00

S100a10
7
9
0.741
0.093
1.14E+00
0.00E+00
0.00E+00

Skap1
7
9
0.739
0.088
8.68E−01
0.00E+00
0.00E+00

Cd28
7
9
0.704
0.037
9.08E−01
3.10E−291
5.48E−284

Cd247
7
9
0.56
0.055
6.59E−01
7.39E−279
1.31E−271

Tcf7
7
9
0.567
0.052
7.85E−01
2.87E−250
5.08E−243

Thy1
7
9
0.548
0.086
7.66E−01
7.64E−240
1.35E−232

Tnfrsf18
7
9
0.511
0.052
6.81E−01
3.25E−186
5.74E−179

Trbc1
7
10
0.666
0.064
1.83E+00
0.00E+00
0.00E+00

Cd3g
7
10
0.968
0.055
1.72E+00
0.00E+00
0.00E+00

Izumo1r
7
10
0.861
0.029
1.62E+00
0.00E+00
0.00E+00

Cd3d
7
10
0.94
0.083
1.54E+00
0.00E+00
0.00E+00

Cd3e
7
10
0.94
0.07
1.54E+00
0.00E+00
0.00E+00

Trac
7
10
0.883
0.05
1.49E+00
0.00E+00
0.00E+00

S100a10
7
10
0.741
0.053
1.19E+00
0.00E+00
0.00E+00

Ms4a4b
7
10
0.695
0.07
1.19E+00
0.00E+00
0.00E+00

Lat
7
10
0.829
0.076
1.17E+00
0.00E+00
0.00E+00

Fyb
7
10
0.809
0.059
1.11E+00
0.00E+00
0.00E+00

S100a11
7
10
0.675
0.09
9.97E−01
0.00E+00
0.00E+00

Cd2
7
10
0.741
0.074
9.65E−01
0.00E+00
0.00E+00

Hcst
7
10
0.746
0.089
9.60E−01
0.00E+00
0.00E+00

Cd28
7
10
0.704
0.013
9.39E−01
0.00E+00
0.00E+00

Skap1
7
10
0.739
0.035
9.24E−01
0.00E+00
0.00E+00

Tcf7
7
10
0.567
0.029
8.17E−01
0.00E+00
0.00E+00

Thy1
7
10
0.548
0.049
8.12E−01
0.00E+00
0.00E+00

Cd247
7
10
0.56
0.025
6.92E−01
0.00E+00
0.00E+00

Tnfrsf18
7
10
0.511
0.024
7.11E−01
8.12E−305
1.44E−297

Ccnd2
7
10
0.508
0.044
6.89E−01
3.76E−300
6.66E−293

Izumo1r
7
11
0.861
0.005
1.64E+00
0.00E+00
0.00E+00

Cd3g
7
11
0.968
0.069
1.64E+00
0.00E+00
0.00E+00

Ifi27l2a
7
11
0.802
0.07
1.60E+00
0.00E+00
0.00E+00

Cd3e
7
11
0.94
0.021
1.57E+00
0.00E+00
0.00E+00

Cd3d
7
11
0.94
0.047
1.57E+00
0.00E+00
0.00E+00

Cd247
7
11
0.56
0.097
6.18E−01
6.59E−169
1.17E−161

Slamf6
7
11
0.506
0.058
6.26E−01
2.89E−160
5.12E−153

Ifi27l2a
7
12
0.802
0.05
1.64E+00
0.00E+00
0.00E+00

Izumo1r
7
12
0.861
0.019
1.62E+00
0.00E+00
0.00E+00

Cd3d
7
12
0.94
0.028
1.59E+00
0.00E+00
0.00E+00

Cd3e
7
12
0.94
0.057
1.53E+00
0.00E+00
0.00E+00

Trac
7
12
0.883
0.014
1.53E+00
0.00E+00
0.00E+00

Cd2
7
12
0.741
0.026
1.03E+00
0.00E+00
0.00E+00

Ms4a4b
7
12
0.695
0.051
1.20E+00
3.69E−294
6.54E−287

Ms4a6b
7
12
0.713
0.08
8.79E−01
1.14E−278
2.01E−271

Cd247
7
12
0.56
0.027
6.88E−01
2.73E−226
4.83E−219

Slamf6
7
12
0.506
0.023
6.66E−01
2.62E−187
4.64E−180

Cd3g
7
14
0.968
0.058
1.66E+00
0.00E+00
0.00E+00

Cd3e
7
14
0.94
0.038
1.53E+00
0.00E+00
0.00E+00

Cd3d
7
14
0.94
0.061
1.53E+00
0.00E+00
0.00E+00

Trac
7
14
0.883
0.033
1.48E+00
2.64E−306
4.67E−299

Lat
7
14
0.829
0.053
1.16E+00
1.88E−298
3.32E−291

Izumo1r
7
14
0.861
0.019
1.60E+00
6.48E−242
1.15E−234

Skap1
7
14
0.739
0.072
8.69E−01
3.49E−239
6.17E−232

Cd2
7
14
0.741
0.058
9.82E−01
3.58E−217
6.34E−210

Cd28
7
14
0.704
0.03
9.15E−01
1.08E−195
1.92E−188

Cd247
7
14
0.56
0.041
6.62E−01
9.06E−191
1.60E−183

Izumo1r
7
15
0.861
0
1.65E+00
7.11E−193
1.26E−185

Cd3g
7
15
0.968
0.04
1.73E+00
3.70E−172
6.55E−165

Cd3d
7
15
0.94
0.013
1.62E+00
2.96E−160
5.24E−153

Izumo1r
7
17
0.861
0.018
1.63E+00
5.44E−235
9.63E−228

Cd3g
7
20
0.968
0.081
1.64E+00
6.23E−254
1.10E−246

Cd3e
7
20
0.94
0.064
1.47E+00
9.72E−237
1.72E−229

Cd3d
7
20
0.94
0.093
1.45E+00
1.67E−228
2.96E−221

Trac
7
20
0.883
0.064
1.46E+00
7.54E−197
1.33E−189

Izumo1r
7
20
0.861
0.034
1.55E+00
1.71E−160
3.02E−153

Cd3e
7
21
0.94
0.064
1.51E+00
1.45E−185
2.56E−178

Cd3d
7
21
0.94
0.064
1.50E+00
1.11E−179
1.96E−172

Lat
7
21
0.829
0.098
1.12E+00
8.93E−178
1.58E−170

Cd3g
7
21
0.968
0.098
1.58E+00
1.06E−171
1.88E−164

Cd3g
7
22
0.968
0.039
1.73E+00
3.01E−248
5.34E−241

Cd3d
7
22
0.94
0.022
1.60E+00
2.68E−239
4.74E−232

Cd3e
7
22
0.94
0.039
1.56E+00
1.40E−230
2.48E−223

Lck
7
22
0.882
0.082
1.22E+00
3.03E−206
5.37E−199

Trac
7
22
0.883
0.013
1.53E+00
6.99E−202
1.24E−194

Lat
7
22
0.829
0.047
1.20E+00
7.06E−182
1.25E−174

Izumo1r
7
22
0.861
0.004
1.64E+00
2.55E−168
4.52E−161

Trbc2
7
24
0.977
0.081
2.25E+00
3.84E−252
6.81E−245

Cd3g
7
24
0.968
0.027
1.69E+00
6.76E−247
1.20E−239

Cd3e
7
24
0.94
0.004
1.60E+00
2.10E−240
3.71E−233

Cd3d
7
24
0.94
0.018
1.61E+00
2.76E−231
4.89E−224

Lck
7
24
0.882
0.058
1.29E+00
1.39E−211
2.45E−204

Trac
7
24
0.883
0.013
1.52E+00
1.54E−195
2.73E−188

Lat
7
24
0.829
0.027
1.22E+00
8.60E−185
1.52E−177

Izumo1r
7
24
0.861
0.013
1.63E+00
3.74E−160
6.63E−153

Trbc2
7
25
0.977
0.063
2.30E+00
5.05E−261
8.93E−254

Cd3g
7
25
0.968
0.027
1.75E+00
3.98E−246
7.05E−239

Cd3e
7
25
0.94
0.009
1.60E+00
7.30E−229
1.29E−221

Cd3d
7
25
0.94
0.018
1.61E+00
7.24E−224
1.28E−216

Coro1a
7
25
0.957
0.1
1.76E+00
4.86E−220
8.61E−213

Limd2
7
25
0.919
0.1
1.57E+00
5.21E−191
9.22E−184

Ptprcap
7
25
0.91
0.063
1.50E+00
3.38E−190
5.98E−183

Trac
7
25
0.883
0.009
1.53E+00
9.75E−182
1.73E−174

Lck
7
25
0.882
0.045
1.28E+00
6.13E−180
1.09E−172

Izumo1r
7
25
0.861
0
1.65E+00
2.79E−167
4.94E−160

Laptm5
7
25
0.9
0.1
1.28E+00
5.99E−166
1.06E−158

Trbc2
7
26
0.977
0.083
2.26E+00
3.43E−253
6.06E−246

Cd3g
7
26
0.968
0.014
1.75E+00
3.10E−251
5.50E−244

Cd3d
7
26
0.94
0.032
1.59E+00
7.47E−233
1.32E−225

Cd3e
7
26
0.94
0.078
1.50E+00
1.33E−225
2.35E−218

Lck
7
26
0.882
0.032
1.31E+00
6.43E−206
1.14E−198

Trac
7
26
0.883
0.005
1.53E+00
3.70E−198
6.55E−191

Izumo1r
7
26
0.861
0.005
1.64E+00
2.77E−163
4.90E−156

Trbc2
7
30
0.977
0.059
2.31E+00
2.58E−180
4.56E−173

Cd3g
7
30
0.968
0.044
1.73E+00
1.44E−168
2.55E−161

Trbc2
7
32
0.977
0.017
2.38E+00
1.60E−167
2.83E−160

Nkg7
8
9
0.983
0.068
2.28E+00
0.00E+00
0.00E+00

Tyrobp
8
9
0.989
0.093
2.27E+00
0.00E+00
0.00E+00

Cd7
8
9
0.779
0.077
1.55E+00
0.00E+00
0.00E+00

Klrd1
8
9
0.908
0.015
1.43E+00
0.00E+00
0.00E+00

S100a10
8
9
0.899
0.093
1.24E+00
0.00E+00
0.00E+00

Il2rb
8
9
0.802
0.041
1.09E+00
0.00E+00
0.00E+00

Klrk1
8
9
0.828
0.005
1.19E+00
2.02E−283
3.58E−276

Ctla2a
8
9
0.697
0.01
1.34E+00
6.60E−282
1.17E−274

Fcer1g
8
9
0.921
0.038
1.63E+00
3.24E−266
5.74E−259

Satb1
8
9
0.607
0.069
7.14E−01
2.09E−236
3.70E−229

Txk
8
9
0.751
0.055
9.45E−01
1.70E−235
3.01E−228

Nabp1
8
9
0.694
0.082
9.67E−01
5.57E−233
9.86E−226

Klri2
8
9
0.542
0.002
8.86E−01
2.65E−232
4.69E−225

Xcl1
8
9
0.532
0.01
1.15E+00
5.71E−226
1.01E−218

Sh2d2a
8
9
0.537
0.052
6.93E−01
3.54E−199
6.26E−192

Dok2
8
9
0.648
0.046
7.46E−01
2.58E−198
4.57E−191

Ptpn22
8
9
0.528
0.038
5.75E−01
5.06E−195
8.95E−188

Bhlhe40
8
9
0.591
0.05
7.18E−01
1.55E−189
2.75E−182

Klrb1c
8
9
0.688
0.012
9.32E−01
6.00E−187
1.06E−179

Eomes
8
9
0.578
0.002
7.33E−01
1.91E−186
3.38E−179

Klre1
8
9
0.703
0
9.51E−01
1.52E−185
2.70E−178

Pglyrp1
8
9
0.51
0.027
5.95E−01
5.35E−177
9.48E−170

Sell
8
9
0.575
0.062
6.79E−01
2.79E−169
4.93E−162

Skap1
8
9
0.554
0.088
5.45E−01
8.74E−169
1.55E−161

Ccl5
8
10
0.993
0.084
3.97E+00
0.00E+00
0.00E+00

Gzma
8
10
0.745
0.05
2.96E+00
0.00E+00
0.00E+00

Nkg7
8
10
0.983
0.045
2.31E+00
0.00E+00
0.00E+00

Tyrobp
8
10
0.989
0.064
2.28E+00
0.00E+00
0.00E+00

Ncr1
8
10
0.951
0.009
1.72E+00
0.00E+00
0.00E+00

Ms4a4b
8
10
0.932
0.07
1.65E+00
0.00E+00
0.00E+00

Fcer1g
8
10
0.921
0.032
1.63E+00
0.00E+00
0.00E+00

Cd7
8
10
0.779
0.043
1.58E+00
0.00E+00
0.00E+00

Klrd1
8
10
0.908
0.007
1.44E+00
0.00E+00
0.00E+00

Trbc1
8
10
0.852
0.064
1.39E+00
0.00E+00
0.00E+00

Vps37b
8
10
0.804
0.074
1.39E+00
0.00E+00
0.00E+00

Selplg
8
10
0.918
0.09
1.35E+00
0.00E+00
0.00E+00

Ctla2a
8
10
0.697
0.008
1.35E+00
0.00E+00
0.00E+00

S100a10
8
10
0.899
0.053
1.30E+00
0.00E+00
0.00E+00

Bcl2
8
10
0.799
0.05
1.30E+00
0.00E+00
0.00E+00

Xcl1
8
10
0.532
0.002
1.20E+00
0.00E+00
0.00E+00

Klrk1
8
10
0.828
0.005
1.18E+00
0.00E+00
0.00E+00

Hcst
8
10
0.861
0.089
1.17E+00
0.00E+00
0.00E+00

Il2rb
8
10
0.802
0.021
1.11E+00
0.00E+00
0.00E+00

Ctsw
8
10
0.789
0.018
1.08E+00
0.00E+00
0.00E+00

Nabp1
8
10
0.694
0.04
1.01E+00
0.00E+00
0.00E+00

Txk
8
10
0.751
0.03
9.77E−01
0.00E+00
0.00E+00

Klre1
8
10
0.703
0.001
9.50E−01
0.00E+00
0.00E+00

Klrb1c
8
10
0.688
0.004
9.41E−01
0.00E+00
0.00E+00

Klri2
8
10
0.542
0.001
8.87E−01
0.00E+00
0.00E+00

S100a11
8
10
0.706
0.09
7.72E−01
0.00E+00
0.00E+00

Dok2
8
10
0.648
0.024
7.71E−01
0.00E+00
0.00E+00

Eomes
8
10
0.578
0.002
7.35E−01
0.00E+00
0.00E+00

Emb
8
10
0.52
0.057
7.30E−01
0.00E+00
0.00E+00

Satb1
8
10
0.607
0.061
7.22E−01
0.00E+00
0.00E+00

Skap1
8
10
0.554
0.035
6.01E−01
1.09E−305
1.92E−298

Ptpn22
8
10
0.528
0.024
5.87E−01
1.50E−305
2.66E−298

Serpinb9
8
10
0.596
0.011
1.00E+00
1.50E−302
2.65E−295

Car2
8
10
0.578
0.1
8.79E−01
2.96E−302
5.24E−295

Fasl
8
10
0.552
0.002
6.73E−01
1.01E−298
1.79E−291

Klre1
8
10
0.548
0.001
9.66E−01
3.41E−295
6.03E−288

Sell
8
10
0.575
0.042
7.00E−01
7.32E−295
1.30E−287

Nr4a1
8
10
0.618
0.093
9.83E−01
1.89E−294
3.34E−287

Id2
8
10
0.606
0.051
1.02E+00
1.75E−285
3.10E−278

Ccl4
8
10
0.579
0.025
2.00E+00
1.26E−281
2.23E−274

Pglyrp1
8
10
0.51
0.034
5.87E−01
5.32E−271
9.43E−264

Serpinb6b
8
10
0.598
0.09
8.01E−01
3.38E−256
5.99E−249

Ccnd2
8
10
0.519
0.044
6.49E−01
1.88E−255
3.34E−248

Ahnak
8
10
0.519
0.018
5.86E−01
3.92E−238
6.95E−231

Tnfaip3
8
10
0.534
0.07
6.06E−01
2.50E−236
4.42E−229

H2-Q7
8
10
0.546
0.101
5.50E−01
7.70E−230
1.36E−222

Gpr171
8
10
0.501
0.076
5.05E−01
7.53E−213
1.33E−205

Eomes
8
11
0.578
0.062
6.59E−01
3.01E−188
5.33E−181

Sell
8
11
0.575
0.094
6.33E−01
3.69E−161
6.53E−154

Ms4a4b
8
12
0.932
0.051
1.66E+00
0.00E+00
0.00E+00

Ncr1
8
12
0.951
0.076
1.62E+00
0.00E+00
0.00E+00

Klrd1
8
12
0.908
0.02
1.41E+00
0.00E+00
0.00E+00

Klrk1
8
12
0.828
0.059
1.12E+00
0.00E+00
0.00E+00

Cd2
8
12
0.681
0.026
8.63E−01
1.17E−278
2.07E−271

Klrb1c
8
12
0.688
0.035
9.02E−01
3.42E−270
6.05E−263

Anxa2
8
12
0.625
0.038
7.75E−01
6.86E−225
1.21E−217

Eomes
8
12
0.578
0.021
7.15E−01
3.08E−219
5.46E−212

Klri2
8
12
0.542
0.025
8.63E−01
1.06E−209
1.88E−202

Klrc1
8
12
0.548
0.017
9.45E−01
5.87E−203
1.04E−195

Xcl1
8
12
0.532
0.033
1.16E+00
1.02E−189
1.80E−182

Fasl
8
12
0.552
0.035
6.33E−01
4.99E−182
8.83E−175

Pglyrp1
8
12
0.51
0.024
5.95E−01
2.59E−180
4.59E−173

Car2
8
12
0.578
0.1
8.61E−01
1.15E−174
2.04E−167

Sell
8
12
0.575
0.081
6.54E−01
3.90E−166
6.90E−159

Gzma
8
13
0.745
0.003
3.01E+00
2.11E−279
3.73E−272

Fcer1g
8
13
0.921
0.017
1.66E+00
5.50E−219
9.75E−212

Ncr1
8
14
0.951
0.077
1.61E+00
3.85E−245
6.82E−238

Ctla2a
8
14
0.697
0.052
1.27E+00
2.60E−192
4.60E−185

Ctsw
8
14
0.789
0.1
9.56E−01
1.88E−190
3.33E−183

Ccl5
8
15
0.993
0.085
3.90E+00
7.57E−296
1.34E−288

Gzma
8
15
0.745
0.032
2.97E+00
3.99E−238
7.07E−231

Gzma
8
16
0.745
0.098
2.26E+00
1.41E−181
2.49E−174

Ccl5
8
18
0.993
0.085
3.77E+00
0.00E+00
0.00E+00

Tyrobp
8
18
0.989
0.06
2.30E+00
0.00E+00
0.00E+00

Ncr1
8
18
0.951
0.007
1.72E+00
7.58E−263
1.34E−255

Klrd1
8
18
0.908
0.028
1.40E+00
4.84E−222
8.57E−215

Fcer1g
8
18
0.921
0.05
1.63E+00
3.56E−217
6.30E−210

Klrk1
8
18
0.828
0.021
1.17E+00
6.13E−178
1.09E−170

Cd7
8
18
0.779
0.05
1.58E+00
1.99E−172
3.52E−165

Ncr1
8
20
0.951
0.089
1.61E+00
1.17E−194
2.08E−187

Klrd1
8
20
0.908
0.093
1.34E+00
5.68E−177
1.00E−169

Ncr1
8
22
0.951
0.086
1.60E+00
5.24E−178
9.28E−171

Klrd1
8
22
0.908
0.043
1.37E+00
8.53E−175
1.51E−167

Nkg7
8
24
0.983
0.076
2.23E+00
2.96E−230
5.24E−223

Ms4a4b
8
24
0.932
0.031
1.69E+00
4.56E−188
8.07E−181

Trbc1
8
24
0.852
0.076
1.34E+00
6.70E−188
1.19E−180

Ncr1
8
24
0.951
0.036
1.67E+00
3.31E−182
5.86E−175

Gimap4
8
24
0.861
0.058
1.23E+00
4.15E−179
7.34E−172

Klrd1
8
24
0.908
0.076
1.32E+00
1.93E−169
3.41E−162

Nkg7
8
25
0.983
0.063
2.28E+00
1.49E−252
2.64E−245

Ncr1
8
25
0.951
0.036
1.69E+00
1.45E−208
2.57E−201

Ms4a4b
8
25
0.932
0.018
1.70E+00
6.98E−198
1.24E−190

Klrd1
8
25
0.908
0.014
1.43E+00
7.14E−184
1.26E−176

Fcer1g
8
25
0.921
0.086
1.54E+00
1.71E−170
3.02E−163

Selplg
8
25
0.918
0.09
1.35E+00
2.29E−165
4.06E−158

Coro1a
8
25
0.91
0.1
1.36E+00
1.65E−164
2.93E−157

Ptprcap
8
25
0.894
0.063
1.25E+00
1.64E−162
2.90E−155

Ms4a4b
8
26
0.932
0.06
1.64E+00
5.99E−191
1.06E−183

Klrd1
8
26
0.908
0.037
1.40E+00
8.99E−178
1.59E−170

Trbc1
8
26
0.852
0.069
1.32E+00
1.40E−176
2.48E−169

Gimap4
8
26
0.861
0.078
1.22E+00
3.37E−163
5.97E−156

Ccl5
8
29
0.993
0.095
3.39E+00
1.57E−163
2.79E−156

Nkg7
8
30
0.983
0.044
2.29E+00
3.81E−172
6.74E−165

Ccl5
8
32
0.993
0.085
3.98E+00
1.18E−179
2.09E−172

Cd52
8
32
0.989
0.094
2.16E+00
1.45E−164
2.56E−157

Cd79b
9
11
0.998
0.048
2.66E+00
3.93E−245
6.95E−238

Cd79a
9
11
0.997
0.019
2.87E+00
5.18E−227
9.17E−220

Aicda
9
11
0.88
0.002
1.53E+00
6.56E−218
1.16E−210

Ms4a1
9
11
0.995
0.007
2.69E+00
5.05E−211
8.94E−204

Ebf1
9
11
0.987
0.004
2.37E+00
4.99E−196
8.83E−189

Mzb1
9
11
0.985
0.029
2.48E+00
1.05E−174
1.85E−167

Rgsl3
9
11
0.948
0.002
2.04E+00
8.72E−171
1.54E−163

Hlfx
9
11
0.675
0.002
1.35E+00
1.81E−164
3.21E−157

Siglecg
9
11
0.79
0.01
1.09E+00
6.20E−163
1.10E−155

H2-DMb2
9
11
0.98
0.036
2.23E+00
1.30E−160
2.31E−153

Smagp
9
11
0.866
0.007
1.37E+00
2.76E−159
4.88E−152

Cd79a
9
12
0.997
0.036
2.85E+00
1.89E−254
3.35E−247

Ms4a1
9
12
0.995
0.02
2.68E+00
3.27E−226
5.79E−219

Aicda
9
12
0.88
0.006
1.53E+00
2.31E−213
4.10E−206

Ebf1
9
12
0.987
0.009
2.36E+00
1.32E−206
2.34E−199

Mzb1
9
12
0.985
0.034
2.48E+00
3.75E−189
6.64E−182

Rgs13
9
12
0.948
0.003
2.04E+00
8.16E−178
1.44E−170

H2-DMb2
9
12
0.98
0.043
2.22E+00
1.50E−169
2.66E−162

Smagp
9
12
0.866
0.002
1.38E+00
6.56E−168
1.16E−160

Stmn1
9
12
0.977
0.036
2.66E+00
2.00E−165
3.54E−158

Vpreb3
9
12
0.894
0.003
2.00E+00
1.88E−163
3.32E−156

Scimp
9
12
0.933
0.008
1.56E+00
1.46E−159
2.58E−152

Siglecg
9
12
0.79
0.012
1.09E+00
4.77E−159
8.45E−152

Cd79a
9
14
0.997
0.081
2.74E+00
0.00E+00
0.00E+00

Ms4a1
9
14
0.995
0.053
2.62E+00
0.00E+00
0.00E+00

Mzb1
9
14
0.985
0.094
2.33E+00
0.00E+00
0.00E+00

Ebf1
9
14
0.987
0.034
2.30E+00
0.00E+00
0.00E+00

Rgs13
9
14
0.948
0.014
2.02E+00
0.00E+00
0.00E+00

Pou2af1
9
14
0.963
0.023
2.01E+00
0.00E+00
0.00E+00

Vpreb3
9
14
0.894
0.014
1.98E+00
0.00E+00
0.00E+00

Chchd10
9
14
0.916
0.085
1.81E+00
0.00E+00
0.00E+00

Iglc3
9
14
0.948
0.092
1.76E+00
0.00E+00
0.00E+00

Eaf2
9
14
0.9
0.034
1.56E+00
0.00E+00
0.00E+00

Aicda
9
14
0.88
0.008
1.52E+00
0.00E+00
0.00E+00

Apitd1
9
14
0.894
0.099
1.35E+00
3.0E−315
5.33E−308

Gcsam
9
14
0.874
0.056
1.48E+00
6.17E−300
1.09E−292

Smagp
9
14
0.866
0.085
1.29E+00
8.32E−283
1.47E−275

Cdl9
9
14
0.801
0.014
1.09E+00
2.81E−278
4.98E−271

Iglc2
9
14
0.847
0.063
1.66E+00
2.23E−276
3.94E−269

Blnk
9
14
0.848
0.088
1.22E+00
2.20E−259
3.90E−252

Bfsp2
9
14
0.775
0.033
1.36E+00
1.88E−247
3.34E−240

Neil1
9
14
0.792
0.058
1.20E+00
4.58E−239
8.10E−232

Cd81
9
14
0.838
0.094
1.12E+00
6.41E−239
1.14E−231

Csrp2
9
14
0.742
0.027
1.00E+00
5.87E−225
1.04E−217

Fcmr
9
14
0.731
0.023
9.44E−01
3.68E−222
6.52E−215

Hlfx
9
14
0.675
0.006
1.34E+00
1.16E−219
2.05E−212

Apobec1
9
14
0.788
0.081
1.00E+00
1.33E−215
2.35E−208

Id3
9
14
0.722
0.031
1.16E+00
2.68E−207
4.75E−200

Slpr2
9
14
0.705
0.02
9.16E−01
9.00E−207
1.59E−199

Lipc
9
14
0.66
0.003
8.78E−01
1.64E−203
2.90E−196

Myl4
9
14
0.714
0.044
1.18E+00
5.61E−199
9.93E−192

Asf1b
9
14
0.75
0.075
1.16E+00
3.18E−196
5.63E−189

Sh2b2
9
14
0.724
0.049
9.44E−01
1.11E−195
1.97E−188

Nuggc
9
14
0.586
0.002
7.58E−01
1.75E−170
3.10E−163

Cd22
9
14
0.642
0.023
8.07E−01
8.94E−170
1.58E−162

Cd79a
9
17
0.997
0.082
2.78E+00
9.84E−183
1.74E−175

Ms4a1
9
17
0.995
0.035
2.66E+00
5.67E−160
l.OOE−152

Stmn1
9
20
0.977
0.081
2.52E+00
2.71E−162
4.80E−155

Cd79a
9
21
0.997
0.098
2.76E+00
0.00E+00
0.00E+00

Ms4a1
9
21
0.995
0.034
2.66E+00
4.15E−303
7.35E−296

Ebf1
9
21
0.987
0.021
2.35E+00
5.78E−277
1.02E−269

Pou2af1
9
21
0.963
0.038
1.99E+00
9.91E−246
1.75E−238

Rgs13
9
21
0.948
0.021
2.02E+00
1.90E−221
3.36E−214

Iglc3
9
21
0.948
0.081
1.84E+00
2.35E−204
4.16E−197

Tnfrsf13c
9
21
0.906
0.043
1.62E+00
5.72E−184
1.01E−176

Eaf2
9
21
0.9
0.026
1.58E+00
8.29E−184
1.47E−176

Aicda
9
21
0.88
0.004
1.53E+00
2.66E−176
4.72E−169

Vpreb3
9
21
0.894
0.034
1.96E+00
1.48E−174
2.61E−167

Cd79a
9
22
0.997
0.06
2.75E+00
5.18E−216
9.16E−209

Ms4a1
9
22
0.995
0.039
2.64E+00
6.47E−211
1.14E−203

Ebf1
9
22
0.987
0.043
2.29E+00
1.98E−188
3.51E−181

Mzb1
9
22
0.985
0.065
2.45E+00
2.95E−179
5.21E−172

Stmn1
9
22
0.977
0.034
2.67E+00
8.71E−174
1.54E−166

Cd24a
9
22
0.976
0.047
2.30E+00
1.89E−161
3.35E−154

Pou2af1
9
22
0.963
0.013
2.04E+00
2.98E−158
5.27E−151

Cd79a
9
24
0.997
0.049
2.84E+00
8.48E−229
1.50E−221

Ms4a1
9
24
0.995
0.045
2.65E+00
2.20E−211
3.89E−204

Mzb1
9
24
0.985
0.058
2.46E+00
1.11E−181
1.97E−174

Stmn1
9
24
0.977
0.058
2.59E+00
6.50E−162
1.15E−154

Pou2af1
9
24
0.963
0.009
2.04E+00
2.88E−159
5.10E−152

Cd79b
9
26
0.998
0.092
2.60E+00
4.40E−200
7.79E−193

Cd79a
9
26
0.997
0.018
2.86E+00
3.10E−193
5.48E−186

Ms4a1
9
26
0.995
0.014
2.68E+00
3.48E−188
6.15E−181

Ebf1
9
26
0.987
0.005
2.37E+00
1.71E−174
3.02E−167

Mzb1
9
26
0.985
0.041
2.46E+00
5.42E−159
9.58E−152

Cd79a
9
34
0.997
0.05
2.82E+00
5.35E−169
9.48E−162

Cd79b
9
35
0.998
0.081
2.61E+00
5.26E−166
9.31E−159

Cd79a
10
11
0.998
0.019
2.63E+00
0.00E+00
0.00E+00

Cd79b
10
11
0.995
0.048
2.50E+00
0.00E+00
0.00E+00

Ms4a1
10
11
0.991
0.007
2.39E+00
0.00E+00
0.00E+00

Ighg1
10
11
0.844
0.072
2.28E+00
0.00E+00
0.00E+00

Ebf1
10
11
0.992
0.004
2.14E+00
0.00E+00
0.00E+00

Mzb1
10
11
0.97
0.029
2.05E+00
0.00E+00
0.00E+00

H2-DMb2
10
11
0.971
0.036
2.04E+00
0.00E+00
0.00E+00

Ifi30
10
11
0.922
0.064
1.75E+00
0.00E+00
0.00E+00

Rgs13
10
11
0.907
0.002
1.62E+00
0.00E+00
0.00E+00

Iglc3
10
11
0.89
0.024
1.50E+00
0.00E+00
0.00E+00

Mef2c
10
11
0.922
0.048
1.45E+00
0.00E+00
0.00E+00

Tnfrsf13c
10
11
0.864
0.016
1.44E+00
0.00E+00
0.00E+00

Sypl
10
11
0.903
0.037
1.42E+00
0.00E+00
0.00E+00

Cd24a
10
11
0.842
0.015
1.33E+00
0.00E+00
0.00E+00

Aicda
10
11
0.833
0.002
1.33E+00
0.00E+00
0.00E+00

Pou2af1
10
11
0.84
0.007
1.29E+00
0.00E+00
0.00E+00

Scimp
10
11
0.855
0.017
1.26E+00
0.00E+00
0.00E+00

Siglecg
10
11
0.794
0.01
1.04E+00
3.4E−316
0.00E+00

Basp1
10
11
0.821
0.026
1.24E+00
1.0E−310
1.88E−303

Iglc2
10
11
0.825
0.027
1.58E+00
6.08E−307
1.08E−299

Eaf2
10
11
0.798
0.006
1.21E+00
1.05E−301
1.86E−294

Apoe
10
11
0.81
0.037
1.86E+00
6.28E−297
1.11E−289

Iglc1
10
11
0.827
0.05
2.19E+00
1.73E−277
3.06E−270

H2-Ob
10
11
0.741
0.007
9.24E−01
3.68E−269
6.53E−262

Cd19
10
11
0.745
0.004
9.18E−01
1.38E−266
2.45E−259

Vpreb3
10
11
0.743
0.012
1.31E+00
5.68E−263
1.01E−255

Plekho1
10
11
0.731
0.008
9.07E−01
2.71E−261
4.80E−254

Fcmr
10
11
0.732
0.004
9.61E−01
9.71E−259
1.72E−251

Ctsh
10
11
0.816
0.07
1.03E+00
6.46E−243
1.14E−235

Pkig
10
11
0.788
0.055
1.09E+00
7.22E−230
1.28E−222

Smagp
10
11
0.691
0.007
9.10E−01
1.52E−229
2.68E−222

Gcsam
10
11
0.674
0.008
9.54E−01
8.41E−220
1.49E−212

Cd22
10
11
0.64
0.002
7.95E−01
2.04E−212
3.61E−205

Pou2f2
10
11
0.792
0.092
9.93E−01
1.12E−211
1.98E−204

Spib
10
11
0.706
0.022
9.31E−01
1.39E−209
2.45E−202

Neil1
10
11
0.705
0.037
9.03E−01
2.01E−201
3.56E−194

Apobec1
10
11
0.68
0.018
7.94E−01
9.30E−201
1.65E−193

Cd81
10
11
0.722
0.042
8.90E−01
9.65E−196
1.71E−188

Blnk
10
11
0.676
0.024
8.51E−01
5.58E−191
9.88E−184

Sh2b2
10
11
0.575
0.004
6.58E−01
8.74E−185
1.55E−177

Dok3
10
11
0.602
0.004
7.14E−01
2.91E−181
5.15E−174

Slpr2
10
11
0.602
0.01
7.65E−01
1.97E−176
3.49E−169

Bfsp2
10
11
0.649
0.03
9.62E−01
1.58E−171
2.80E−164

Apitd1
10
11
0.641
0.023
7.57E−01
3.86E−169
6.83E−162

H2-Oa
10
11
0.647
0.039
7.65E−01
2.66E−166
4.71E−159

Cd79a
10
12
0.998
0.036
2.61E+00
0.00E+00
0.00E+00

Ms4a1
10
12
0.991
0.02
2.38E+00
0.00E+00
0.00E+00

Ighg1
10
12
0.844
0.073
2.27E+00
0.00E+00
0.00E+00

Ebf1
10
12
0.992
0.009
2.13E+00
0.00E+00
0.00E+00

Mzb1
10
12
0.97
0.034
2.04E+00
0.00E+00
0.00E+00

H2-DMb2
10
12
0.971
0.043
2.02E+00
0.00E+00
0.00E+00

Ifi30
10
12
0.922
0.069
1.73E+00
0.00E+00
0.00E+00

Rgs13
10
12
0.907
0.003
1.62E+00
0.00E+00
0.00E+00

Iglc3
10
12
0.89
0.019
1.50E+00
0.00E+00
0.00E+00

Mef2c
10
12
0.922
0.021
1.47E+00
0.00E+00
0.00E+00

Tnfrsf13c
10
12
0.864
0.009
1.45E+00
0.00E+00
0.00E+00

Sypl
10
12
0.903
0.089
1.36E+00
0.00E+00
0.00E+00

Aicda
10
12
0.833
0.006
1.32E+00
0.00E+00
0.00E+00

Pou2af1
10
12
0.84
0.006
1.29E+00
0.00E+00
0.00E+00

Scimp
10
12
0.855
0.008
1.27E+00
0.00E+00
0.00E+00

Siglecg
10
12
0.794
0.012
1.04E+00
2.28E−307
4.03E−300

Eaf2
10
12
0.798
0.005
1.21E+00
5.39E−306
9.55E−299

Iglc2
10
12
0.825
0.037
1.57E+00
1.75E−295
3.10E−288

Apoe
10
12
0.81
0.053
1.84E+00
1.86E−279
3.29E−272

Vpreb3
10
12
0.743
0.003
1.31E+00
2.87E−275
5.08E−268

Cd24a
10
12
0.842
0.069
1.25E+00
7.23E−268
1.28E−260

H2-Ob
10
12
0.741
0.01
9.21E−01
9.22E−262
1.63E−254

Iglc1
10
12
0.827
0.07
2.18E+00
1.01E−261
1.79E−254

Plekho1
10
12
0.731
0.01
9.05E−01
1.95E−255
3.44E−248

Cd19
10
12
0.745
0.012
9.10E−01
3.19E−253
5.65E−246

Fcmr
10
12
0.732
0.012
9.52E−01
1.68E−244
2.97E−237

Smagp
10
12
0.691
0.002
9.15E−01
2.09E−237
3.70E−230

Pkig
10
12
0.788
0.064
1.08E+00
1.18E−226
2.08E−219

Ctsh
10
12
0.816
0.098
1.00E+00
2.17E−223
3.84E−216

Lat2
10
12
0.763
0.047
9.49E−01
7.05E−223
1.25E−215

Gcsam
10
12
0.674
0.007
9.55E−01
4.03E−221
7.13E−214

Spib
10
12
0.706
0.021
9.31E−01
2.91E−212
5.15E−205

Apobec1
10
12
0.68
0.012
8.04E−01
1.39E−211
2.47E−204

Cd22
10
12
0.64
0.007
7.91E−01
2.53E−202
4.48E−195

Neil1
10
12
0.705
0.042
8.98E−01
2.33E−197
4.12E−190

Il21r
10
12
0.655
0.016
8.25E−01
1.03E−190
1.82E−183

Bfsp2
10
12
0.649
0.015
9.76E−01
4.45E−190
7.87E−183

Blnk
10
12
0.676
0.03
8.44E−01
2.70E−185
4.78E−178

Dok3
10
12
0.602
0.006
7.12E−01
1.02E−178
1.81E−171

Sh2b2
10
12
0.575
0.009
6.54E−01
2.16E−173
3.83E−166

Slpr2
10
12
0.602
0.016
7.59E−01
2.93E−168
5.18E−161

Apitd1
10
12
0.641
0.033
7.47E−01
4.53E−161
8.02E−154

Napsa
10
12
0.687
0.068
8.57E−01
1.52E−158
2.69E−151

H2-Aa
10
13
0.999
0.076
3.49E+00
3.61E−168
6.40E−161

Cd79a
10
14
0.998
0.081
2.50E+00
0.00E+00
0.00E+00

Ms4a1
10
14
0.991
0.053
2.31E+00
0.00E+00
0.00E+00

Ebf1
10
14
0.992
0.034
2.07E+00
0.00E+00
0.00E+00

Mzb1
10
14
0.97
0.094
1.90E+00
0.00E+00
0.00E+00

Rgs13
10
14
0.907
0.014
1.60E+00
0.00E+00
0.00E+00

Iglc3
10
14
0.89
0.092
1.36E+00
0.00E+00
0.00E+00

Aicda
10
14
0.833
0.008
1.31E+00
0.00E+00
0.00E+00

Pou2af1
10
14
0.84
0.023
1.26E+00
0.00E+00
0.00E+00

Eaf2
10
14
0.798
0.034
1.17E+00
2.4E−310
4.25E−303

Tnfrsf13c
10
14
0.864
0.091
1.35E+00
0.00E+00
6.31E−302

Iglc2
10
14
0.825
0.063
1.47E+00
3.70E−287
6.55E−280

Cd19
10
14
0.745
0.014
9.08E−01
2.99E−273
5.30E−266

Vpreb3
10
14
0.743
0.014
1.30E+00
1.62E−259
2.88E−252

Fcmr
10
14
0.732
0.023
9.28E−01
2.95E−258
5.22E−251

Neil1
10
14
0.705
0.058
8.77E−01
8.25E−220
1.46E−212

Bfsp2
10
14
0.649
0.033
9.55E−01
2.51E−218
4.44E−211

Blnk
10
14
0.676
0.088
7.73E−01
1.36E−210
2.41E−203

Smagp
10
14
0.691
0.085
8.24E−01
2.47E−207
4.38E−200

Cd81
10
14
0.722
0.094
8.11E−01
2.30E−205
4.07E−198

Cd22
10
14
0.64
0.023
7.68E−01
1.11E−204
1.96E−197

Apitd1
10
14
0.641
0.099
6.56E−01
5.55E−200
9.83E−193

Slpr2
10
14
0.602
0.02
7.49E−01
8.78E−195
1.55E−187

Gcsam
10
14
0.674
0.056
8.38E−01
1.22E−194
2.15E−187

Apobec1
10
14
0.68
0.081
7.29E−01
2.83E−193
5.00E−186

Lipc
10
14
0.523
0.003
6.71E−01
3.47E−184
6.15E−177

Chchd10
10
14
0.594
0.085
7.19E−01
1.96E−159
3.46E−152

Cd79a
10
17
0.998
0.082
2.54E+00
0.00E+00
0.00E+00

Ms4a1
10
17
0.991
0.035
2.36E+00
0.00E+00
0.00E+00

Ebf1
10
17
0.992
0.018
2.11E+00
0.00E+00
0.00E+00

H2-DMb2
10
17
0.971
0.059
2.00E+00
2.87E−294
5.09E−287

Mzb1
10
17
0.97
0.041
2.04E+00
9.13E−292
1.62E−284

Rgs13
10
17
0.907
0.006
1.62E+00
8.52E−237
1.51E−229

Mef2c
10
17
0.922
0.041
1.44E+00
5.71E−228
1.01E−220

Iglc3
10
17
0.89
0.035
1.48E+00
4.72E−203
8.36E−196

Scimp
10
17
0.855
0.018
1.26E+00
9.09E−189
1.61E−181

Aicda
10
17
0.833
0.006
1.32E+00
1.73E−186
3.07E−179

Tnfrsf13c
10
17
0.864
0.038
1.42E+00
l.OOE−183
1.78E−176

Ighg1
10
17
0.844
0.082
2.27E+00
1.20E−177
2.12E−170

Pou2af1
10
17
0.84
0.023
1.27E+00
5.60E−177
9.91E−170

Cd24a
10
17
0.842
0.035
1.31E+00
1.10E−170
1.94E−163

Siglecg
10
17
0.794
0.009
1.04E+00
9.13E−166
1.62E−158

Eaf2
10
17
0.798
0.009
1.20E+00
9.41E−163
1.66E−155

Ebf1
10
18
0.992
0.036
2.11E+00
1.11E−295
1.97E−288

Ms4a1
10
18
0.991
0.078
2.32E+00
8.46E−294
1.50E−286

H2-DMb2
10
18
0.971
0.096
1.95E+00
1.38E−246
2.44E−239

Mzb1
10
18
0.97
0.053
2.03E+00
4.86E−245
8.61E−238

Mef2c
10
18
0.922
0.021
1.48E+00
7.94E−201
1.41E−193

Rgs13
10
18
0.907
0.018
1.60E+00
5.24E−190
9.27E−183

Ifi30
10
18
0.922
0.078
1.73E+00
2.12E−178
3.75E−171

Iglc3
10
18
0.89
0.053
1.47E+00
1.78E−161
3.15E−154

Cd79a
10
19
0.998
0.072
2.58E+00
7.16E−230
1.27E−222

Cd79b
10
19
0.995
0.064
2.49E+00
6.93E−205
1.23E−197

Ebf1
10
19
0.992
0.016
2.13E+00
4.79E−199
8.48E−192

Ms4a1
10
19
0.991
0.028
2.37E+00
1.22E−192
2.17E−185

Rgs13
10
20
0.907
0.064
1.48E+00
2.65E−185
4.70E−178

Aicda
10
20
0.833
0.017
1.31E+00
4.12E−180
7.29E−173

Scimp
10
20
0.855
0.059
1.22E+00
2.59E−161
4.59E−154

Cd79a
10
21
0.998
0.098
2.53E+00
5.07E−300
8.97E−293

Ms4a1
10
21
0.991
0.034
2.36E+00
1.40E−227
2.48E−220

Aicda
10
21
0.833
0.004
1.32E+00
1.38E−198
2.45E−191

Ebf1
10
21
0.992
0.021
2.12E+00
1.28E−193
2.27E−186

Rgs13
10
21
0.907
0.021
1.60E+00
3.72E−188
6.58E−181

Iglc3
10
21
0.89
0.081
1.43E+00
7.41E−186
1.31E−178

Pou2af1
10
21
0.84
0.038
1.24E+00
5.44E−183
9.63E−176

Eaf2
10
21
0.798
0.026
1.19E+00
1.06E−168
1.88E−161

Tnfrsf13c
10
21
0.864
0.043
1.41E+00
8.31E−166
1.47E−158

Cd79a
10
22
0.998
0.06
2.51E+00
5.54E−304
9.80E−297

Ms4a1
10
22
0.991
0.039
2.34E+00
8.01E−280
1.42E−272

Ebf1
10
22
0.992
0.043
2.06E+00
2.12E−267
3.75E−260

Mzb1
10
22
0.97
0.065
2.01E+00
3.91E−244
6.92E−237

Rgs13
10
22
0.907
0.013
1.61E+00
5.35E−209
9.47E−202

Iglc3
10
22
0.89
0.069
1.43E+00
3.11E−182
5.51E−175

Aicda
10
22
0.833
0.017
1.31E+00
2.75E−180
4.88E−173

Pou2af1
10
22
0.84
0.013
1.28E+00
1.97E−176
3.50E−169

Tnfrsf13c
10
22
0.864
0.017
1.43E+00
1.11E−175
1.97E−168

Cd24a
10
22
0.842
0.047
1.30E+00
6.21E−160
1.10E−152

Cd79a
10
24
0.998
0.049
2.60E+00
0.00E+00
0.00E+00

Ms4a1
10
24
0.991
0.045
2.35E+00
5.18E−283
9.17E−276

Mzb1
10
24
0.97
0.058
2.02E+00
1.75E−255
3.10E−248

Rgs13
10
24
0.907
0.013
1.60E+00
3.34E−202
5.91E−195

Aicda
10
24
0.833
0.013
1.30E+00
5.11E−175
9.05E−168

Pou2af1
10
24
0.84
0.009
1.29E+00
2.44E−174
4.31E−167

Iglc3
10
24
0.89
0.081
1.39E+00
7.47E−174
1.32E−166

Tnfrsf13c
10
24
0.864
0.013
1.44E+00
2.27E−173
4.01E−166

Scimp
10
24
0.855
0.031
1.25E+00
4.54E−170
8.04E−163

Eaf2
10
24
0.798
0
1.21E+00
2.57E−161
4.54E−154

Cd79a
10
25
0.998
0.027
2.62E+00
3.18E−255
5.64E−248

Cd79b
10
25
0.995
0.009
2.54E+00
3.64E−242
6.45E−235

Ms4a1
10
25
0.991
0
2.40E+00
3.99E−234
7.06E−227

Coro1a
10
25
0.989
0.1
2.32E+00
2.55E−223
4.51E−216

Mzb1
10
25
0.97
0.023
2.05E+00
3.06E−190
5.42E−183

Cd37
10
25
0.965
0.014
1.79E+00
4.75E−190
8.40E−183

H2-DMb2
10
25
0.971
0.045
2.03E+00
5.72E−189
1.01E−181

Rhoh
10
25
0.96
0.036
1.69E+00
2.97E−177
5.26E−170

Laptm5
10
25
0.96
0.1
1.69E+00
4.12E−159
7.28E−152

Limd2
10
25
0.962
0.1
1.72E+00
1.90E−158
3.36E−151

Cd79a
10
26
0.998
0.018
2.62E+00
8.82E−302
1.56E−294

Cd79b
10
26
0.995
0.092
2.44E+00
1.67E−298
2.95E−291

Ms4a1
10
26
0.991
0.014
2.38E+00
7.48E−275
1.32E−267

Ebf1
10
26
0.992
0.005
2.14E+00
5.80E−273
1.03E−265

H2-DMb2
10
26
0.971
0.069
1.98E+00
1.09E−246
1.94E−239

Mzb1
10
26
0.97
0.041
2.03E+00
1.91E−245
3.38E−238

Mef2c
10
26
0.922
0.037
1.44E+00
8.93E−198
1.58E−190

Ifi30
10
26
0.922
0.092
1.69E+00
1.66E−187
2.94E−180

Iglc3
10
26
0.89
0.069
1.41E+00
8.92E−169
1.58E−161

Aicda
10
26
0.833
0.005
1.32E+00
3.12E−167
5.52E−160

Tnfrsf13c
10
26
0.864
0.009
1.44E+00
7.36E−167
1.30E−159

Pou2af1
10
26
0.84
0.009
1.29E+00
2.00E−162
3.53E−155

Scimp
10
26
0.855
0.018
1.26E+00
1.38E−161
2.44E−154

Cd79a
10
30
0.998
0.052
2.57E+00
3.89E−191
6.88E−184

Cd79b
10
30
0.995
0.059
2.45E+00
3.12E−172
5.52E−165

Ms4a1
10
30
0.991
0.022
2.35E+00
1.41E−162
2.50E−155

Ebf1
10
30
0.992
0.022
2.12E+00
8.97E−162
1.59E−154

Cd79a
10
32
0.998
0.009
2.64E+00
2.54E−167
4.50E−160

Cd79a
10
33
0.998
0.057
2.59E+00
3.57E−182
6.31E−175

Cd79b
10
33
0.995
0.076
2.48E+00
1.51E−174
2.67E−167

Ms4a1
10
33
0.991
0.01
2.39E+00
8.34E−160
1.48E−152

Cd79b
10
35
0.995
0.081
2.46E+00
1.84E−177
3.26E−170

H2-DMb2
10
35
0.971
0.101
1.94E+00
1.09E−160
1.93E−153

Xcl1
11
12
0.908
0.033
1.93E+00
0.00E+00
0.00E+00

Ncr1
11
12
0.952
0.076
1.65E+00
0.00E+00
0.00E+00

Klrd1
11
12
0.853
0.02
1.28E+00
0.00E+00
0.00E+00

Klrk1
11
12
0.88
0.059
1.25E+00
0.00E+00
0.00E+00

Ms4a4b
11
12
0.817
0.051
1.21E+00
4.74E−300
8.39E−293

Car2
11
12
0.783
0.1
1.23E+00
7.03E−250
1.24E−242

Klrc1
11
12
0.595
0.017
1.02E+00
2.45E−194
4.34E−187

Klrblf
11
12
0.579
0.025
7.00E−01
1.51E−182
2.67E−175

Fasl
11
12
0.598
0.035
6.67E−01
3.16E−176
5.60E−169

Ncr1
11
14
0.952
0.077
1.64E+00
1.55E−194
2.74E−187

Ccl5
11
18
0.973
0.085
3.04E+00
7.30E−233
1.29E−225

Ncr1
11
18
0.952
0.007
1.75E+00
1.45E−231
2.57E−224

Fcer1g
11
18
0.966
0.05
1.65E+00
4.66E−229
8.25E−222

Tyrobp
11
18
0.945
0.06
1.98E+00
3.97E−219
7.03E−212

Cd7
11
18
0.924
0.05
1.91E+00
5.81E−203
1.03E−195

Xcl1
11
18
0.908
0.039
1.63E+00
2.51E−179
4.45E−172

Klrk1
11
18
0.88
0.021
1.30E+00
6.65E−177
1.18E−169

Klrd1
11
18
0.853
0.028
1.26E+00
6.33E−159
1.12E−151

Ncr1
11
20
0.952
0.089
1.64E+00
2.56E−176
4.53E−169

Nkg7
11
24
0.964
0.076
1.79E+00
6.88E−184
1.22E−176

Ncr1
11
24
0.952
0.036
1.70E+00
1.22E−160
2.16E−153

Gimap4
11
24
0.944
0.058
1.50E+00
5.77E−159
1.02E−151

Nkg7
11
25
0.964
0.063
1.84E+00
2.29E−193
4.06E−186

Ncr1
11
25
0.952
0.036
1.72E+00
8.48E−185
1.50E−177

Fcer1g
11
25
0.966
0.086
1.57E+00
4.05E−177
7.18E−170

Xcl1
11
25
0.908
0.009
1.96E+00
4.57E−161
8.09E−154

Gata3
12
14
0.946
0.066
1.76E+00
1.57E−197
2.78E−190

Hs3st1
12
17
0.846
0.003
1.70E+00
2.51E−189
4.44E−182

Lmo4
12
18
0.988
0.089
2.52E+00
4.76E−262
8.43E−255

Hs3st1
12
18
0.846
0.007
1.69E+00
2.17E−162
3.85E−155

Lmo4
12
19
0.988
0.084
2.51E+00
1.10E−206
1.95E−199

Gata3
12
20
0.946
0.076
1.70E+00
6.31E−171
1.12E−163

Gata3
12
22
0.946
0.082
1.70E+00
2.26E−159
4.00E−152

Trbc1
12
24
0.946
0.076
1.59E+00
9.97E−173
1.76E−165

Gata3
12
24
0.946
0.031
1.81E+00
2.45E−167
4.34E−160

Gata3
12
25
0.946
0.027
1.81E+00
1.05E−175
1.86E−168

Trbc1
12
25
0.946
0.059
1.58E+00
1.28E−165
2.27E−158

Trbc1
12
26
0.946
0.069
1.57E+00
1.27E−169
2.25E−162

Gata3
12
26
0.946
0.028
1.77E+00
1.10E−163
1.94E−156

Cd7
17
18
0.988
0.05
3.01E+00
2.24E−179
3.96E−172

TABLE 3

Differential expression analysis between cells from mice treated with OVA or PBS

in each cell type in PP (Table 3A) and LP (Table 3B) regions, related to FIG. 2.

A

percentage of
percentage of

expressing
expressing

cluster
cells in OVA-
cells in PBS-
LN (average

p value,

gene
ID
treated group
treated group
fold change)
p value
adjusted

Tsc22d3
1
0.811
0.538
0.720
9.66E−129
7.61E−123

Wdr89
1
0.983
0.941
0.366
3.01E−124
1.13E−118

Txnip
1
0.617
0.378
0.759
8.02E−98
1.05E−92

Uba52
1
0.97
0.917
0.334
1.80E−65
1.42E−60

Ddit4
1
0.348
0.209
0.532
7.46E−61
4.19E−56

Bcl2
1
0.806
0.701
0.510
3.76E−55
1.64E−50

Cd74
1
0.428
0.525
−0.311
1.07E−49
3.67E−45

Jund
1
0.667
0.761
−0.352
2.35E−45
6.62E−41

Zfp36l2
1
0.566
0.302
0.837
1.47E−42
3.31E−38

Il7r
1
0.406
0.248
0.548
6.56E−39
1.03E−34

Pik3ip1
1
0.495
0.361
0.321
2.62E−28
2.46E−24

Hspa8
1
0.965
0.967
−0.313
6.56E−25
4.61E−21

Hsp90ab1
1
0.82
0.867
−0.340
3.66E−23
2.34E−19

Pdcd4
1
0.626
0.487
0.353
3.23E−22
1.93E−18

Klf6
1
0.388
0.474
−0.370
1.86E−20
9.96E−17

Igha
1
0.166
0.1
0.552
8.23E−20
4.26E−16

Ifngr1
1
0.434
0.268
0.579
8.75E−19
3.92E−15

Ltb
1
0.826
0.847
−0.221
6.06E−18
2.54E−14

Dnaja1
1
0.551
0.652
−0.413
8.11E−18
3.32E−14

Iglc1
1
0.072
0.158
−0.884
1.12E−16
4.05E−13

Gramd3
1
0.386
0.222
0.593
1.12E−16
4.05E−13

Klhl6
1
0.299
0.211
0.353
1.21E−16
4.37E−13

DynIl1
1
0.64
0.721
−0.268
1.48E−16
5.28E−13

Rnaset2a
1
0.583
0.437
0.311
1.65E−15
5.21E−12

Ube2s
1
0.472
0.361
0.296
1.79E−15
5.56E−12

Ucp2
1
0.764
0.636
0.295
4.56E−15
1.35E−11

Igkc
1
0.531
0.601
−0.321
5.17E−15
1.52E−11

Grcc10
1
0.557
0.414
0.357
1.95E−14
5.45E−11

Ubb
1
0.989
0.983
−0.168
2.36E−14
6.45E−11

Srsf3
1
0.505
0.555
−0.236
5.37E−14
1.44E−10

VgIl4
1
0.274
0.322
−0.350
2.14E−13
5.48E−10

H2-Aa
1
0.211
0.228
−0.202
8.81E−13
2.04E−09

Tnfrsf18
1
0.392
0.27
0.456
1.03E−12
2.35E−09

Dnajb1
1
0.222
0.347
−0.700
1.25E−12
2.85E−09

Cd40lg
1
0.138
0.194
−0.506
2.21E−12
4.84E−09

Tpm3
1
0.621
0.5
0.239
6.64E−12
1.38E−08

Hsp90aa1
1
0.558
0.661
−0.444
1.07E−10
1.97E−07

Tnfsf8
1
0.181
0.099
0.471
2.28E−10
3.97E−07

Ppp1r15a
1
0.281
0.311
−0.226
2.29E−10
3.98E−07

Atf4
1
0.218
0.261
−0.316
2.32E−10
4.01E−07

Ms4a4b
1
0.921
0.858
0.189
2.65E−10
4.50E−07

Ahsa1
1
0.247
0.307
−0.359
2.91E−10
4.92E−07

Fos
1
0.22
0.261
−0.255
4.30E−10
7.12E−07

Klhdc1
1
0.327
0.225
0.342
6.23E−10
1.00E−06

Kbtbd11
1
0.314
0.219
0.355
1.78E−09
2.69E−06

Neat1
1
0.274
0.3
−0.269
1.80E−09
2.72E−06

Nrip1
1
0.247
0.16
0.455
2.74E−09
4.01E−06

Lrrc58
1
0.437
0.35
0.238
3.24E−09
4.69E−06

Klhdc2
1
0.281
0.201
0.399
4.01E−09
5.75E−06

Rcsd1
1
0.336
0.254
0.283
4.20E−09
6.01E−06

Ptpn22
1
0.215
0.132
0.489
4.66E−09
6.61E−06

Cacybp
1
0.305
0.393
−0.386
4.92E−09
6.94E−06

Ier5
1
0.244
0.268
−0.208
6.69E−09
9.22E−06

Socs1
1
0.226
0.134
0.523
1.68E−08
2.16E−05

Arl4c
1
0.459
0.495
−0.184
1.76E−08
2.26E−05

Bcl11b
1
0.431
0.474
−0.226
2.69E−08
3.36E−05

Hspe1
1
0.659
0.677
−0.196
3.26E−08
4.03E−05

Ctsc
1
0.155
0.113
0.285
3.64E−08
4.48E−05

Gstp1
1
0.332
0.258
0.204
5.44E−08
6.48E−05

Acp5
1
0.414
0.325
0.201
6.23E−08
7.30E−05

Tagap
1
0.183
0.207
−0.202
6.30E−08
7.35E−05

Slbp
1
0.129
0.164
−0.301
1.11E−07
1.23E−04

Ets1
1
0.625
0.519
0.186
1.19E−07
1.33E−04

Rbm3
1
0.838
0.758
0.201
1.41E−07
1.54E−04

Cetn3
1
0.259
0.188
0.240
2.79E−07
2.89E−04

Cd3e
1
0.891
0.815
0.170
3.56E−07
3.58E−04

Bloc1s1
1
0.162
0.107
0.349
4.83E−07
4.76E−04

Jun
1
0.23
0.297
−0.389
6.84E−07
6.50E−04

Crlf3
1
0.594
0.469
0.317
7.03E−07
6.67E−04

Ywhah
1
0.377
0.408
−0.167
1.38E−06
1.24E−03

Cnp
1
0.487
0.409
0.157
1.53E−06
1.37E−03

Dusp2
1
0.367
0.292
0.319
1.56E−06
1.39E−03

Slfn2
1
0.55
0.432
0.289
2.16E−06
1.88E−03

Sfpq
1
0.311
0.341
−0.216
2.48E−06
2.14E−03

2810474O19Rik
1
0.318
0.262
0.171
2.93E−06
2.47E−03

Stip1
1
0.177
0.221
−0.355
3.30E−06
2.76E−03

Mfap1b
1
0.157
0.123
0.161
4.60E−06
3.70E−03

Tubb4b
1
0.183
0.206
−0.198
4.76E−06
3.80E−03

Stt3b
1
0.281
0.206
0.252
5.25E−06
4.14E−03

Tmem50a
1
0.595
0.485
0.195
6.05E−06
4.69E−03

Sh3bp5
1
0.239
0.171
0.302
8.96E−06
6.65E−03

Smad7
1
0.301
0.322
−0.160
1.15E−05
8.28E−03

Zfp36
1
0.196
0.223
−0.174
1.54E−05
1.07E−02

Atp1b3
1
0.692
0.595
0.188
1.56E−05
1.09E−02

Sdhaf1
1
0.167
0.097
0.511
1.61E−05
1.12E−02

Grb2
1
0.202
0.266
−0.357
1.74E−05
1.20E−02

Rhof
1
0.195
0.214
−0.180
1.98E−05
1.34E−02

Rheb
1
0.208
0.229
−0.179
2.01E−05
1.36E−02

H2-T23
1
0.252
0.173
0.288
3.34E−05
2.16E−02

Fkbp4
1
0.273
0.315
−0.251
4.39E−05
2.76E−02

Zfos1
1
0.299
0.316
−0.155
6.66E−05
3.94E−02

Anapc16
1
0.199
0.144
0.279
7.73E−05
4.49E−02

Ywhab
1
0.328
0.358
−0.172
8.66E−05
4.93E−02

Irf1
1
0.155
0.187
−0.208
8.82E−05
5.00E−02

Zfp36l2
2
0.64
0.218
1.626
2.64E−112
4.65E−107

Tsc22d3
2
0.806
0.526
0.816
3.02E−56
1.40E−51

Sesn1
2
0.32
0.099
1.317
1.40E−32
1.62E−28

Ptpn22
2
0.213
0.093
0.999
2.68E−21
1.51E−17

Ddit4
2
0.216
0.126
0.714
5.00E−20
2.62E−16

Fam107b
2
0.53
0.334
0.653
7.67E−20
4.00E−16

Iglc2
2
0.861
0.924
−0.275
1.01E−17
4.06E−14

Hs3st1
2
0.183
0.072
0.958
4.47E−16
1.49E−12

Iglc3
2
0.86
0.905
−0.196
9.41E−16
3.05E−12

Pik3ip1
2
0.231
0.131
0.568
1.42E−15
4.49E−12

Ccnd3
2
0.321
0.171
0.710
1.41E−14
4.00E−11

Plaur
2
0.273
0.093
1.207
2.91E−14
7.91E−11

Pdcd4
2
0.426
0.32
0.482
1.82E−11
3.57E−08

Btg1
2
0.996
0.99
0.251
5.67E−11
1.07E−07

Cd69
2
0.502
0.367
0.462
7.31E−11
1.37E−07

Swap70
2
0.326
0.373
−0.259
1.59E−10
2.83E−07

Srgn
2
0.867
0.745
0.347
1.93E−10
3.39E−07

Cd24a
2
0.582
0.596
−0.234
4.21E−10
6.98E−07

Egln2
2
0.311
0.169
0.709
1.07E−09
1.67E−06

Rsrp1
2
0.481
0.564
−0.342
4.13E−08
5.03E−05

Ltb
2
0.837
0.853
−0.251
5.43E−08
6.48E−05

Cxcr4
2
0.671
0.477
0.491
7.26E−08
8.37E−05

Sorl1
2
0.4
0.267
0.459
2.08E−07
2.21E−04

Sla
2
0.251
0.145
0.642
2.53E−07
2.64E−04

Smad7
2
0.212
0.13
0.479
2.58E−07
2.68E−04

Cd180
2
0.281
0.334
−0.252
3.15E−07
3.23E−04

Sdhaf1
2
0.31
0.228
0.473
3.64E−07
3.66E−04

Txnip
2
0.403
0.255
0.611
4.70E−07
4.65E−04

Egr1
2
0.289
0.198
0.594
6.79E−07
6.46E−04

Gpr171
2
0.445
0.272
0.554
7.35E−07
6.95E−04

Smc6
2
0.673
0.58
0.212
8.29E−07
7.73E−04

Malat1
2
1
0.999
−0.189
1.92E−06
1.69E−03

Ly6d
2
0.253
0.339
−0.495
2.27E−06
1.97E−03

Sypl
2
0.434
0.307
0.405
4.65E−06
3.73E−03

Napsa
2
0.749
0.638
0.242
4.95E−06
3.92E−03

Acp5
2
0.411
0.313
0.289
5.31E−06
4.18E−03

P2ry10
2
0.308
0.167
0.629
8.14E−06
6.11E−03

Hhex
2
0.277
0.309
−0.177
1.12E−05
8.07E−03

Il10ra
2
0.155
0.081
0.643
1.96E−05
1.34E−02

1110059E24Rik
2
0.313
0.204
0.447
2.73E−05
1.80E−02

Scd1
2
0.48
0.345
0.338
2.75E−05
1.81E−02

Jmjd1c
2
0.222
0.177
0.252
3.83E−05
2.45E−02

Stk17b
2
0.77
0.63
0.315
3.85E−05
2.45E−02

Cd47
2
0.587
0.464
0.328
4.50E−05
2.82E−02

Btg2
2
0.767
0.632
0.450
5.96E−05
3.59E−02

Zfand5
2
0.161
0.213
−0.399
6.22E−05
3.72E−02

Bend5
2
0.21
0.151
0.306
6.81E−05
4.02E−02

Sgms1
2
0.263
0.159
0.537
8.69E−05
4.94E−02

Jund
3
0.82
0.94
−0.733
2.95E−112
4.65E−107

Id2
3
0.923
0.738
0.591
1.26E−87
1.42E−82

Pim1
3
0.754
0.884
−0.496
4.49E−72
4.42E−67

Nfkbia
3
0.801
0.905
−0.415
5.12E−63
3.36E−58

Klf4
3
0.19
0.407
−1.015
1.81E−52
7.14E−48

Tgif1
3
0.407
0.6
−0.586
4.81E−50
1.72E−45

Hk2
3
0.253
0.457
−0.836
1.71E−49
5.61E−45

Junb
3
0.957
0.971
−0.156
8.61E−48
2.71E−43

Gimap1
3
0.793
0.61
0.500
1.66E−47
5.02E−43

Dusp5
3
0.535
0.687
−0.410
7.77E−45
2.04E−40

Nr4a1
3
0.607
0.752
−0.338
8.83E−43
2.05E−38

Dusp1
3
0.628
0.769
−0.335
5.48E−42
1.17E−37

Sla
3
0.745
0.528
0.626
2.36E−41
4.77E−37

Nfkbiz
3
0.425
0.586
−0.520
7.49E−41
1.47E−36

Prr7
3
0.176
0.343
−0.936
9.56E−41
1.84E−36

AY036118
3
0.388
0.411
−0.405
1.72E−40
3.23E−36

Mcpt1
3
0.19
0.036
1.670
2.37E−40
4.33E−36

Defa24
3
0.04
0.178
−1.549
5.34E−40
9.56E−36

Ifrd1
3
0.255
0.436
−0.719
1.46E−39
2.55E−35

Kdm6b
3
0.291
0.454
−0.672
3.57E−39
6.12E−35

Ubb
3
0.996
0.999
−0.215
3.92E−39
6.56E−35

Fam110a
3
0.22
0.394
−0.748
4.57E−38
6.92E−34

Gadd45b
3
0.533
0.698
−0.196
2.97E−37
4.33E−33

Maff
3
0.435
0.573
−0.425
2.69E−32
3.07E−28

Bhlhe40
3
0.635
0.734
−0.329
1.81E−31
2.00E−27

Ppp1r15a
3
0.312
0.473
−0.550
2.34E−31
2.55E−27

Tnfaip3
3
0.453
0.575
−0.311
4.47E−31
4.82E−27

Txnip
3
0.222
0.08
1.243
2.01E−30
2.09E−26

Vps37b
3
0.551
0.657
−0.438
4.05E−30
4.09E−26

Lmna
3
0.101
0.226
−1.191
5.81E−30
5.79E−26

Gimap6
3
0.841
0.722
0.343
1.67E−29
1.63E−25

Fosb
3
0.272
0.413
−0.583
1.90E−29
1.82E−25

Il22
3
0.188
0.33
−0.772
4.09E−28
3.79E−24

Cd69
3
0.68
0.767
−0.330
7.25E−28
6.42E−24

Bcl2
3
0.679
0.535
0.594
2.16E−27
1.83E−23

Irf7
3
0.155
0.294
−0.904
3.28E−26
2.56E−22

Uhrf2
3
0.495
0.624
−0.452
3.96E−26
3.03E−22

Nfkb1
3
0.352
0.463
−0.558
6.87E−26
5.15E−22

Igha
3
0.477
0.282
0.516
8.76E−26
6.45E−22

Nfkbid
3
0.316
0.454
−0.489
1.85E−24
1.28E−20

Dok1
3
0.367
0.198
0.611
4.60E−24
3.09E−20

Pnrc1
3
0.752
0.826
−0.247
1.44E−23
9.52E−20

Rel
3
0.129
0.253
−0.749
2.98E−23
1.93E−19

Litaf
3
0.246
0.372
−0.544
4.98E−23
3.16E−19

Gimap9
3
0.472
0.304
0.525
2.44E−22
1.48E−18

Nmrk1
3
0.092
0.204
−0.763
6.05E−22
3.55E−18

Atf3
3
0.086
0.19
−0.803
6.89E−22
4.02E−18

Coq10b
3
0.268
0.384
−0.483
7.50E−21
4.07E−17

Taf10
3
0.26
0.402
−0.563
8.81E−20
4.50E−16

Gimap5
3
0.579
0.431
0.446
8.97E−20
4.54E−16

Sik1
3
0.17
0.281
−0.640
9.96E−20
4.99E−16

Btg1
3
0.977
0.978
−0.163
1.28E−19
6.33E−16

Tsc22d3
3
0.514
0.347
0.622
1.43E−19
6.97E−16

Ikzf2
3
0.663
0.742
−0.369
3.39E−19
1.60E−15

Rsrp1
3
0.623
0.492
0.268
3.47E−19
1.62E−15

Nr4a3
3
0.197
0.3
−0.600
3.69E−19
1.72E−15

Ahr
3
0.538
0.397
0.447
5.05E−19
2.34E−15

Rgs2
3
0.535
0.633
−0.297
5.75E−19
2.62E−15

Cdkn1a
3
0.082
0.177
−0.870
8.51E−19
3.83E−15

Phlda1
3
0.248
0.38
−0.522
2.57E−18
1.12E−14

Ncoa7
3
0.755
0.627
0.345
2.84E−18
1.23E−14

D16Ertd472e
3
0.223
0.311
−0.484
5.45E−18
2.29E−14

Ffar2
3
0.752
0.642
0.294
7.23E−18
2.98E−14

Egr1
3
0.192
0.294
−0.541
1.27E−17
5.02E−14

Zc3h12a
3
0.237
0.338
−0.483
1.53E−17
6.00E−14

Rasl11a
3
0.346
0.216
0.766
1.77E−17
6.86E−14

Cited4
3
0.479
0.346
0.361
4.36E−17
1.65E−13

Serpinb9
3
0.367
0.448
−0.428
5.58E−17
2.08E−13

Ier5l
3
0.067
0.153
−1.214
9.93E−17
3.62E−13

Mir142hg
3
0.077
0.161
−0.709
1.29E−16
4.60E−13

Nabp1
3
0.544
0.591
−0.340
1.87E−16
6.64E−13

Zfp36l2
3
0.523
0.364
0.563
3.72E−16
1.27E−12

Igkc
3
0.661
0.527
0.304
4.32E−16
1.45E−12

Ubc
3
0.347
0.457
−0.378
1.66E−15
5.22E−12

Bcl2a1d
3
0.407
0.488
−0.357
2.09E−15
6.44E−12

Slc16a6
3
0.176
0.267
−0.490
4.79E−15
1.41E−11

Crem
3
0.291
0.372
−0.456
5.75E−15
1.68E−11

Cd74
3
0.43
0.53
−0.422
1.31E−14
3.73E−11

Il2rg
3
0.76
0.791
−0.199
1.95E−14
5.45E−11

Furin
3
0.367
0.454
−0.360
6.03E−14
1.62E−10

Fosl2
3
0.337
0.427
−0.340
6.29E−14
1.67E−10

Slfn2
3
0.435
0.311
0.459
7.64E−14
2.01E−10

Icos
3
0.43
0.502
−0.325
1.02E−13
2.67E−10

Emb
3
0.903
0.922
−0.182
1.09E−13
2.83E−10

Nr4a2
3
0.112
0.186
−0.662
1.32E−13
3.42E−10

Cd83
3
0.211
0.303
−0.369
1.43E−13
3.68E−10

Traf1
3
0.557
0.627
−0.266
3.07E−13
7.70E−10

Alyref
3
0.127
0.23
−0.688
3.57E−13
8.86E−10

Dusp2
3
0.313
0.194
0.870
7.85E−13
1.86E−09

Sqstm1
3
0.365
0.456
−0.328
8.72E−13
2.03E−09

Rora
3
0.734
0.775
−0.228
1.57E−12
3.51E−09

Gnai2
3
0.583
0.673
−0.341
1.87E−12
4.17E−09

Il7r
3
0.934
0.891
0.206
3.05E−12
6.56E−09

Serpinb6b
3
0.421
0.497
−0.223
4.37E−12
9.26E−09

Ramp3
3
0.316
0.37
−0.470
9.85E−12
2.00E−08

Ptp4a2
3
0.538
0.618
−0.235
1.77E−11
3.51E−08

Gna13
3
0.394
0.45
−0.291
1.92E−11
3.76E−08

Sla2
3
0.295
0.19
0.465
2.62E−11
5.11E−08

Slpr4
3
0.182
0.097
0.601
6.96E−11
1.31E−07

Cish
3
0.39
0.287
0.423
9.27E−11
1.72E−07

Neat1
3
0.46
0.349
0.291
1.37E−10
2.45E−07

Fcer1g
3
0.914
0.895
0.188
2.11E−10
3.69E−07

Tagap
3
0.277
0.352
−0.196
2.30E−10
3.98E−07

Rnf19b
3
0.287
0.351
−0.411
4.10E−10
6.82E−07

2010300C02Rik
3
0.509
0.407
0.315
4.65E−10
7.65E−07

Icam1
3
0.144
0.219
−0.479
4.80E−10
7.88E−07

Amica1
3
0.405
0.306
0.371
5.80E−10
9.38E−07

Odc1
3
0.227
0.284
−0.409
6.27E−10
1.01E−06

Actr3
3
0.72
0.67
0.227
8.43E−10
1.34E−06

Ppp2ca
3
0.307
0.405
−0.395
1.04E−09
1.63E−06

Klrk1
3
0.733
0.75
−0.160
1.05E−09
1.65E−06

Hist1h1c
3
0.3
0.204
0.664
1.05E−09
1.65E−06

Sec11a
3
0.441
0.351
0.300
1.14E−09
1.78E−06

Csrnp1
3
0.258
0.326
−0.236
1.25E−09
1.92E−06

Nrip1
3
0.627
0.673
−0.162
1.31E−09
2.01E−06

Rilpl2
3
0.284
0.183
0.478
2.33E−09
3.46E−06

Rinl
3
0.624
0.521
0.233
2.45E−09
3.61E−06

H2-Q7
3
0.393
0.459
−0.237
2.58E−09
3.78E−06

Ptpn7
3
0.355
0.266
0.326
3.15E−09
4.57E−06

Neurl3
3
0.446
0.516
−0.209
5.65E−09
7.93E−06

Pdrg1
3
0.265
0.174
0.377
6.42E−09
8.88E−06

Rnf125
3
0.099
0.158
−0.583
6.81E−09
9.36E−06

Chmp4b
3
0.356
0.432
−0.295
6.87E−09
9.42E−06

Cd160
3
0.564
0.449
0.275
8.12E−09
1.10E−05

Ifi47
3
0.265
0.172
0.465
8.87E−09
1.19E−05

Arpc5l
3
0.353
0.261
0.341
9.63E−09
1.29E−05

Ifi203
3
0.47
0.376
0.352
1.02E−08
1.35E−05

Stom
3
0.165
0.091
0.580
1.15E−08
1.52E−05

Cytip
3
0.516
0.551
−0.185
1.60E−08
2.07E−05

Rab19
3
0.178
0.11
0.484
2.36E−08
2.99E−05

Kcnk1
3
0.45
0.35
0.325
2.49E−08
3.12E−05

Ccrl2
3
0.146
0.204
−0.395
2.92E−08
3.64E−05

Jagn1
3
0.156
0.087
0.602
3.06E−08
3.80E−05

Orai1
3
0.293
0.354
−0.265
3.72E−08
4.57E−05

Amd1
3
0.169
0.232
−0.397
3.85E−08
4.72E−05

Dbp
3
0.188
0.126
0.465
4.22E−08
5.12E−05

Gimap7
3
0.598
0.519
0.236
4.58E−08
5.52E−05

Nfil3
3
0.154
0.21
−0.381
4.99E−08
5.98E−05

Cmtm6
3
0.27
0.18
0.417
5.69E−08
6.77E−05

Tmem243
3
0.246
0.315
−0.347
6.06E−08
7.14E−05

Gimap3
3
0.905
0.859
0.189
6.58E−08
7.66E−05

Ptger2
3
0.204
0.139
0.460
6.94E−08
8.05E−05

Fam195b
3
0.287
0.201
0.360
7.37E−08
8.47E−05

Asb2
3
0.551
0.469
0.246
8.68E−08
9.91E−05

Tspan32
3
0.178
0.108
0.515
8.87E−08
1.01E−04

Frmd4b
3
0.169
0.23
−0.389
9.08E−08
1.03E−04

Tob2
3
0.253
0.306
−0.243
9.74E−08
1.10E−04

Ssna1
3
0.299
0.21
0.352
1.38E−07
1.52E−04

Klf2
3
0.272
0.327
−0.271
1.54E−07
1.69E−04

Tvp23b
3
0.17
0.095
0.546
1.78E−07
1.93E−04

Sdhd
3
0.276
0.186
0.419
2.51E−07
2.63E−04

Tbx21
3
0.169
0.109
0.524
2.57E−07
2.68E−04

Gem
3
0.561
0.61
−0.167
2.98E−07
3.07E−04

Map3k14
3
0.155
0.217
−0.422
3.09E−07
3.18E−04

Sat1
3
0.665
0.599
0.179
3.33E−07
3.38E−04

Tomm5
3
0.372
0.282
0.314
3.78E−07
3.79E−04

4921524J17Rik
3
0.153
0.091
0.521
4.49E−07
4.45E−04

Prex1
3
0.365
0.271
0.372
4.96E−07
4.86E−04

Trpc4ap
3
0.344
0.263
0.320
5.24E−07
5.11E−04

Ube2g2
3
0.252
0.172
0.369
5.59E−07
5.41E−04

Gimap8
3
0.238
0.151
0.472
5.81E−07
5.61E−04

Smap2
3
0.369
0.442
−0.258
6.66E−07
6.36E−04

Kit
3
0.411
0.458
−0.204
6.69E−07
6.38E−04

Tifa
3
0.196
0.124
0.459
7.52E−07
7.10E−04

P2ry10
3
0.261
0.318
−0.229
7.55E−07
7.11E−04

Ccnl1
3
0.379
0.44
−0.180
8.06E−07
7.54E−04

Tox
3
0.253
0.171
0.492
8.57E−07
7.97E−04

Mdfic
3
0.437
0.345
0.292
1.03E−06
9.48E−04

Serpinb1a
3
0.768
0.784
−0.178
1.09E−06
9.93E−04

Rlim
3
0.148
0.199
−0.386
1.30E−06
1.18E−03

Timm10b
3
0.351
0.254
0.295
1.36E−06
1.22E−03

F2r
3
0.355
0.412
−0.242
1.52E−06
1.35E−03

Tgoln1
3
0.262
0.322
−0.234
1.71E−06
1.51E−03

Gpcpd1
3
0.187
0.246
−0.328
1.83E−06
1.62E−03

Bcl2a1b
3
0.15
0.194
−0.350
2.38E−06
2.06E−03

VgIl4
3
0.24
0.29
−0.332
2.43E−06
2.09E−03

Ccdc115
3
0.218
0.151
0.408
2.71E−06
2.31E−03

Arl6ip5
3
0.476
0.388
0.229
2.79E−06
2.37E−03

Ddx3x
3
0.353
0.403
−0.175
2.88E−06
2.43E−03

Polr2a
3
0.209
0.26
−0.277
3.08E−06
2.59E−03

Gcnt2
3
0.258
0.305
−0.265
3.87E−06
3.16E−03

Ahcyl2
3
0.623
0.551
0.192
4.48E−06
3.61E−03

H2-Eb1
3
0.162
0.212
−0.312
4.63E−06
3.72E−03

Dusp4
3
0.158
0.211
−0.322
4.87E−06
3.87E−03

Oard1
3
0.176
0.122
0.412
5.55E−06
4.36E−03

Ormdl3
3
0.195
0.129
0.363
6.00E−06
4.66E−03

Gpr171
3
0.382
0.279
0.299
6.36E−06
4.91E−03

Zc3hav1
3
0.223
0.271
−0.209
6.73E−06
5.15E−03

Ezr
3
0.322
0.365
−0.189
6.82E−06
5.21E−03

Clk1
3
0.55
0.585
−0.156
7.20E−06
5.48E−03

Zkscan3
3
0.157
0.105
0.422
7.50E−06
5.68E−03

Klrc1
3
0.225
0.156
0.505
8.30E−06
6.21E−03

Plekhg1
3
0.255
0.312
−0.320
8.53E−06
6.37E−03

Tbc1d10c
3
0.471
0.415
0.204
8.69E−06
6.48E−03

Gjb2
3
0.209
0.263
−0.286
8.75E−06
6.52E−03

Rnf166
3
0.351
0.271
0.250
8.89E−06
6.61E−03

Tcrg-C1
3
0.671
0.607
0.219
9.69E−06
7.15E−03

Clec2d
3
0.243
0.172
0.363
9.72E−06
7.17E−03

Snx20
3
0.194
0.129
0.403
1.02E−05
7.47E−03

Rnf114
3
0.251
0.188
0.288
1.04E−05
7.63E−03

Smim11
3
0.365
0.286
0.307
1.10E−05
8.01E−03

Ptprcap
3
0.818
0.753
0.186
1.17E−05
8.39E−03

Timm13
3
0.556
0.475
0.211
1.23E−05
8.79E−03

Ndel1
3
0.167
0.212
−0.336
1.31E−05
9.33E−03

Supt4a
3
0.672
0.601
0.195
1.37E−05
9.70E−03

Emd
3
0.293
0.343
−0.185
1.41E−05
9.94E−03

Rnf5
3
0.194
0.129
0.419
1.44E−05
1.01E−02

BC031181
3
0.502
0.543
−0.166
1.60E−05
1.12E−02

Mxd1
3
0.269
0.32
−0.211
1.63E−05
1.13E−02

Rgs3
3
0.25
0.178
0.356
1.79E−05
1.23E−02

Gatad1
3
0.153
0.208
−0.322
1.83E−05
1.26E−02

Stat4
3
0.297
0.321
−0.222
1.92E−05
1.31E−02

Tmx1
3
0.199
0.153
0.318
2.53E−05
1.69E−02

Nudt16l1
3
0.183
0.121
0.403
2.76E−05
1.82E−02

Gnb1
3
0.395
0.452
−0.269
2.88E−05
1.89E−02

Fam184b
3
0.232
0.183
0.317
3.00E−05
1.97E−02

Tuba1c
3
0.125
0.162
−0.301
3.03E−05
1.99E−02

Pten
3
0.205
0.263
−0.336
3.04E−05
1.99E−02

Klrb1f
3
0.413
0.338
0.210
3.35E−05
2.17E−02

Fyn
3
0.169
0.223
−0.338
3.65E−05
2.34E−02

Bloc1s2
3
0.159
0.106
0.414
3.90E−05
2.49E−02

Commd6
3
0.238
0.171
0.343
4.08E−05
2.58E−02

Tuba1a
3
0.214
0.258
−0.209
4.09E−05
2.59E−02

Ppt2
3
0.389
0.332
0.224
4.28E−05
2.70E−02

Scn1b
3
0.138
0.186
−0.340
4.92E−05
3.05E−02

Birc3
3
0.297
0.337
−0.173
4.99E−05
3.09E−02

Skil
3
0.198
0.247
−0.266
5.04E−05
3.11E−02

Tmem261
3
0.211
0.142
0.365
5.28E−05
3.24E−02

Ube2s
3
0.433
0.47
−0.154
5.28E−05
3.24E−02

4930523C07Rik
3
0.386
0.426
−0.187
5.83E−05
3.53E−02

C4b
3
0.321
0.26
0.336
5.89E−05
3.56E−02

Traf2
3
0.19
0.137
0.321
5.89E−05
3.56E−02

Rbm4b
3
0.114
0.159
−0.349
5.90E−05
3.56E−02

4930453N24Rik
3
0.237
0.183
0.309
5.97E−05
3.59E−02

Triap1
3
0.167
0.116
0.346
6.00E−05
3.60E−02

Ptpn22
3
0.603
0.508
0.266
6.06E−05
3.64E−02

Il18r1
3
0.626
0.561
0.165
6.22E−05
3.72E−02

Podnl1
3
0.66
0.594
0.171
6.29E−05
3.75E−02

Nt5e
3
0.216
0.164
0.329
7.59E−05
4.42E−02

Pnrc2
3
0.191
0.148
0.224
7.74E−05
4.49E−02

Ppp1r3b
3
0.16
0.195
−0.172
8.39E−05
4.81E−02

Jund
4
0.888
0.978
−0.773
4.29E−124
1.13E−118

Klf4
4
0.284
0.583
−1.032
4.37E−69
3.82E−64

Junb
4
0.957
0.98
−0.249
7.45E−65
5.33E−60

Lmna
4
0.241
0.503
−1.267
2.12E−60
1.11E−55

Ncoa7
4
0.899
0.725
0.635
3.60E−60
1.77E−55

Dusp1
4
0.657
0.816
−0.419
4.71E−45
1.28E−40

Pim1
4
0.688
0.839
−0.372
8.88E−45
2.26E−40

Rasl11a
4
0.737
0.504
0.766
2.69E−42
5.89E−38

Fam110a
4
0.453
0.62
−0.604
4.10E−39
6.72E−35

Sla
4
0.819
0.608
0.624
1.04E−36
1.50E−32

B930036N10Rik
4
0.377
0.159
0.957
9.56E−34
1.26E−29

Ifrd1
4
0.37
0.551
−0.531
1.21E−33
1.50E−29

Ubb
4
0.997
1
−0.219
1.22E−33
1.50E−29

Nfkbia
4
0.882
0.937
−0.305
3.74E−33
4.46E−29

Gimap1
4
0.735
0.537
0.488
6.73E−33
7.91E−29

Maff
4
0.554
0.688
−0.378
8.53E−32
9.60E−28

Fosb
4
0.561
0.668
−0.453
4.03E−30
4.09E−26

Bcl2
4
0.912
0.804
0.403
1.05E−29
1.04E−25

Kdm6b
4
0.324
0.491
−0.629
2.70E−27
2.26E−23

Emb
4
0.822
0.864
−0.325
3.20E−27
2.65E−23

Ahr
4
0.448
0.264
0.772
1.57E−26
1.25E−22

Prr7
4
0.192
0.354
−0.719
1.91E−26
1.51E−22

Ffar2
4
0.669
0.487
0.537
3.71E−26
2.86E−22

AY036118
4
0.316
0.415
−0.746
8.43E−26
6.26E−22

Rora
4
0.674
0.77
−0.391
1.57E−25
1.14E−21

Hspa1a
4
0.308
0.173
0.397
5.71E−25
4.05E−21

Pnrc1
4
0.805
0.864
−0.272
1.65E−24
1.15E−20

Phlda1
4
0.292
0.469
−0.447
1.97E−22
1.21E−18

Gimap6
4
0.721
0.573
0.417
3.67E−22
2.17E−18

Cd83
4
0.504
0.632
−0.288
5.17E−21
2.83E−17

Igha
4
0.463
0.305
0.385
8.55E−20
4.40E−16

Nmrk1
4
0.262
0.395
−0.442
2.64E−19
1.25E−15

Rilpl2
4
0.356
0.189
0.762
5.33E−19
2.45E−15

Tnfaip3
4
0.51
0.62
−0.220
5.42E−19
2.48E−15

Dusp5
4
0.443
0.57
−0.400
5.87E−19
2.66E−15

Actg1
4
0.938
0.964
−0.209
1.09E−18
4.84E−15

Id2
4
0.921
0.805
0.376
3.64E−18
1.56E−14

Odc1
4
0.786
0.816
−0.296
4.30E−18
1.83E−14

Ppp1r15a
4
0.312
0.424
−0.441
7.06E−18
2.93E−14

Igkc
4
0.718
0.569
0.306
8.21E−18
3.35E−14

Avpi1
4
0.203
0.313
−0.575
1.09E−17
4.34E−14

Vps37b
4
0.489
0.593
−0.376
1.12E−17
4.47E−14

Gem
4
0.727
0.813
−0.217
5.78E−17
2.15E−13

Nfkb1
4
0.415
0.523
−0.507
4.11E−16
1.40E−12

Atf3
4
0.19
0.308
−0.487
5.16E−16
1.71E−12

Traf1
4
0.59
0.663
−0.296
6.90E−16
2.26E−12

Rrad
4
0.294
0.412
−0.763
1.10E−15
3.50E−12

Sertad1
4
0.091
0.185
−0.838
1.72E−15
5.37E−12

Tnfsf14
4
0.172
0.074
1.043
3.02E−15
9.14E−12

Sqstm1
4
0.467
0.557
−0.345
3.13E−15
9.45E−12

Crem
4
0.343
0.431
−0.494
4.12E−15
1.23E−11

Hk2
4
0.184
0.286
−0.731
4.51E−15
1.34E−11

Neurl3
4
0.301
0.412
−0.324
1.14E−14
3.28E−11

Defa24
4
0.076
0.169
−0.827
1.37E−14
3.89E−11

Ier5l
4
0.09
0.202
−1.300
1.65E−14
4.66E−11

Ubc
4
0.417
0.508
−0.308
2.10E−14
5.80E−11

Zc3h12a
4
0.336
0.43
−0.358
3.83E−14
1.04E−10

Ube2s
4
0.511
0.581
−0.264
3.26E−13
8.14E−10

H2-Q7
4
0.321
0.439
−0.400
4.20E−13
1.03E−09

Tgif1
4
0.522
0.585
−0.211
4.99E−13
1.21E−09

Uhrf2
4
0.677
0.743
−0.213
5.36E−13
1.30E−09

Gnai2
4
0.596
0.701
−0.411
8.35E−13
1.96E−09

Pcyt1a
4
0.101
0.19
−0.727
9.33E−13
2.16E−09

Il22
4
0.3
0.4
−0.341
1.71E−12
3.83E−09

Pdrg1
4
0.255
0.154
0.546
2.24E−12
4.89E−09

Cish
4
0.393
0.255
0.530
2.75E−12
5.93E−09

Ccng2
4
0.257
0.316
−0.410
1.27E−11
2.56E−08

Nfkbiz
4
0.422
0.524
−0.247
1.63E−11
3.25E−08

Skil
4
0.293
0.365
−0.374
1.64E−11
3.26E−08

Gimap5
4
0.488
0.339
0.470
4.63E−11
8.83E−08

Rsrp1
4
0.613
0.53
0.273
1.19E−10
2.18E−07

Tpm4
4
0.338
0.432
−0.351
1.20E−10
2.18E−07

Mir142hg
4
0.1
0.164
−0.659
1.28E−10
2.32E−07

Sik1
4
0.221
0.322
−0.485
1.49E−10
2.67E−07

Ifngr1
4
0.594
0.65
−0.210
3.17E−10
5.29E−07

Socs1
4
0.38
0.452
−0.304
3.94E−10
6.58E−07

Nfkbie
4
0.242
0.325
−0.368
4.10E−10
6.82E−07

Dok1
4
0.336
0.214
0.446
4.37E−10
7.21E−07

Tuba1a
4
0.187
0.275
−0.471
4.88E−10
7.97E−07

Sdhaf1
4
0.466
0.343
0.404
7.78E−10
1.24E−06

Slc15a3
4
0.199
0.275
−0.484
1.00E−09
1.58E−06

Egr1
4
0.483
0.557
−0.338
1.14E−09
1.78E−06

Slfn2
4
0.243
0.152
0.583
1.17E−09
1.81E−06

Opa3
4
0.091
0.16
−0.602
1.50E−09
2.28E−06

Cotl1
4
0.674
0.736
−0.196
1.66E−09
2.51E−06

Isy1
4
0.245
0.326
−0.344
2.01E−09
3.00E−06

Litaf
4
0.223
0.305
−0.470
2.17E−09
3.22E−06

Ccdc71l
4
0.154
0.257
−0.629
3.10E−09
4.51E−06

Ptp4a1
4
0.268
0.305
−0.253
3.57E−09
5.14E−06

Birc3
4
0.361
0.426
−0.276
4.40E−09
6.28E−06

Cryaa
4
0.104
0.162
−0.447
4.59E−09
6.53E−06

Lta
4
0.333
0.213
0.712
5.92E−09
8.28E−06

Hist1h1c
4
0.285
0.182
0.597
6.38E−09
8.85E−06

Dbp
4
0.38
0.252
0.474
6.96E−09
9.53E−06

Coq10b
4
0.313
0.386
−0.298
7.17E−09
9.80E−06

Atf4
4
0.396
0.454
−0.263
7.42E−09
1.01E−05

Cytip
4
0.386
0.428
−0.282
7.84E−09
1.06E−05

Gna13
4
0.348
0.412
−0.293
8.52E−09
1.15E−05

Emd
4
0.387
0.439
−0.261
9.35E−09
1.25E−05

Socs3
4
0.293
0.362
−0.202
9.71E−09
1.30E−05

Mdfic
4
0.402
0.267
0.439
1.17E−08
1.55E−05

Csrp1
4
0.158
0.21
−0.549
1.30E−08
1.71E−05

Mmd
4
0.476
0.339
0.473
1.54E−08
1.99E−05

Amica1
4
0.313
0.206
0.422
1.88E−08
2.41E−05

Tsix
4
0.153
0.28
−0.771
2.38E−08
3.01E−05

Klf2
4
0.265
0.366
−0.198
2.73E−08
3.42E−05

D16Ertd472e
4
0.175
0.248
−0.412
3.09E−08
3.83E−05

Klrk1
4
0.133
0.219
−0.613
6.25E−08
7.30E−05

Ttc19
4
0.152
0.23
−0.499
6.38E−08
7.43E−05

S100a6
4
0.603
0.517
0.370
6.87E−08
7.98E−05

Rgs3
4
0.282
0.187
0.447
7.43E−08
8.53E−05

Clec2d
4
0.261
0.165
0.489
9.09E−08
1.03E−04

Serpinb6b
4
0.2
0.26
−0.432
1.10E−07
1.22E−04

Neat1
4
0.502
0.378
0.447
1.25E−07
1.38E−04

Ppp2ca
4
0.336
0.429
−0.432
1.27E−07
1.40E−04

Cdkn1a
4
0.256
0.319
−0.202
1.72E−07
1.87E−04

Icos
4
0.236
0.288
−0.291
2.08E−07
2.21E−04

Tubb4b
4
0.347
0.396
−0.252
2.30E−07
2.42E−04

Nedd8
4
0.781
0.67
0.234
2.57E−07
2.68E−04

Tspan32
4
0.395
0.298
0.324
2.84E−07
2.93E−04

Map3k14
4
0.133
0.202
−0.515
3.33E−07
3.39E−04

Dnaja1
4
0.705
0.747
−0.300
3.53E−07
3.57E−04

Saraf
4
0.557
0.581
−0.187
4.03E−07
4.01E−04

Tuba4a
4
0.156
0.206
−0.342
4.91E−07
4.83E−04

Cd69
4
0.737
0.779
−0.153
5.93E−07
5.72E−04

Azin1
4
0.135
0.192
−0.472
6.34E−07
6.08 E−04

Minos1
4
0.768
0.696
0.218
6.36E−07
6.08 E−04

Klf13
4
0.417
0.498
−0.255
6.70E−07
6.38E−04

Rassf5
4
0.31
0.193
0.506
7.28E−07
6.89E−04

2310001H17Rik
4
0.214
0.133
0.484
7.78E−07
7.30E−04

4921524J17Rik
4
0.161
0.097
0.531
7.82E−07
7.33E−04

Tcrg-C1
4
0.36
0.255
0.484
9.86E−07
9.09E−04

2010300C02Rik
4
0.518
0.411
0.310
1.02E−06
9.35E−04

Alyref
4
0.141
0.239
−0.564
1.04E−06
9.54E−04

Ramp3
4
0.224
0.289
−0.380
1.14E−06
1.04E−03

VgIl4
4
0.338
0.398
−0.302
1.16E−06
1.05E−03

Gnb1
4
0.419
0.506
−0.255
1.44E−06
1.29E−03

Asb2
4
0.548
0.471
0.320
1.45E−06
1.30E−03

Taf10
4
0.297
0.403
−0.422
1.48E−06
1.32E−03

Trps1
4
0.17
0.228
−0.444
1.58E−06
1.40E−03

Cacybp
4
0.293
0.208
0.291
2.10E−06
1.83E−03

Taf7
4
0.144
0.2
−0.409
2.16E−06
1.88E−03

Scn1b
4
0.314
0.371
−0.273
2.37E−06
2.05E−03

Mast4
4
0.467
0.512
−0.207
2.54E−06
2.18E−03

Bin3
4
0.235
0.155
0.452
2.67E−06
2.29E−03

Ppp1r16b
4
0.302
0.327
−0.157
2.84E−06
2.41E−03

Furin
4
0.382
0.433
−0.203
2.91E−06
2.46E−03

Rgs1
4
0.498
0.536
−0.221
2.98E−06
2.51E−03

Amd1
4
0.192
0.265
−0.353
4.81E−06
3.83E−03

Itgav
4
0.175
0.227
−0.394
4.91E−06
3.90E−03

H2-T23
4
0.264
0.322
−0.260
6.24E−06
4.82E−03

S100a10
4
0.866
0.794
0.215
6.58E−06
5.06E−03

Plekhg1
4
0.231
0.295
−0.229
7.07E−06
5.39E−03

Ptpn7
4
0.337
0.238
0.323
7.78E−06
5.86E−03

Git2
4
0.3
0.215
0.350
9.21E−06
6.83E−03

Tagap
4
0.461
0.366
0.423
1.02E−05
7.46E−03

Morf4l2
4
0.317
0.366
−0.252
1.10E−05
8.01E−03

Egln3
4
0.172
0.217
−0.350
1.10E−05
8.01E−03

Mbnl2
4
0.162
0.233
−0.436
1.10E−05
8.01E−03

Gimap3
4
0.536
0.43
0.275
1.12E−05
8.07E−03

Zfand5
4
0.252
0.306
−0.245
1.12E−05
8.09E−03

Ssna1
4
0.294
0.21
0.346
1.32E−05
9.39E−03

Raf1
4
0.232
0.149
0.457
1.36E−05
9.64E−03

Tgoln1
4
0.286
0.324
−0.209
1.42E−05
1.00E−02

Trim8
4
0.223
0.138
0.530
1.48E−05
1.04E−02

Rel
4
0.19
0.252
−0.354
1.67E−05
1.16E−02

Cwc25
4
0.12
0.163
−0.463
1.74E−05
1.20E−02

Sat1
4
0.744
0.652
0.222
1.78E−05
1.23E−02

Gatad1
4
0.155
0.2
−0.316
1.89E−05
1.29E−02

Fibp
4
0.178
0.212
−0.268
2.16E−05
1.46E−02

Il2ra
4
0.457
0.342
0.378
2.23E−05
1.50E−02

Gcnt2
4
0.144
0.201
−0.352
2.58E−05
1.72E−02

Vegfa
4
0.131
0.174
−0.252
2.61E−05
1.73E−02

Il18r1
4
0.605
0.507
0.193
2.62E−05
1.74E−02

Timm13
4
0.592
0.522
0.230
3.06E−05
2.00E−02

Rcn2
4
0.258
0.302
−0.225
3.10E−05
2.02E−02

Irs2
4
0.149
0.201
−0.372
3.24E−05
2.10E−02

Fam46a
4
0.099
0.152
−0.500
3.45E−05
2.22E−02

Leng9
4
0.128
0.179
−0.375
4.41E−05
2.77E−02

Herpud1
4
0.33
0.387
−0.214
5.16E−05
3.18E−02

Dnajb9
4
0.18
0.236
−0.322
5.37E−05
3.29E−02

Zc3hav1
4
0.145
0.184
−0.303
5.44E−05
3.33E−02

1600014C10Rik
4
0.185
0.117
0.467
5.46E−05
3.34E−02

Tsc22d3
4
0.489
0.413
0.359
5.46E−05
3.34E−02

Ptger2
4
0.299
0.218
0.347
5.75E−05
3.49E−02

Rpa3
4
0.175
0.101
0.541
6.42E−05
3.82E−02

Tnf
4
0.245
0.172
0.465
6.52E−05
3.86E−02

Txk
4
0.529
0.59
−0.188
6.82E−05
4.02E−02

Sec11a
4
0.376
0.297
0.283
7.54E−05
4.40E−02

Serpina3g
4
0.587
0.512
0.347
7.67E−05
4.46E−02

Bzw1
4
0.321
0.354
−0.190
8.62E−05
4.92E−02

Rnf19b
4
0.427
0.454
−0.242
8.70E−05
4.94E−02

Irf2
4
0.306
0.216
0.312
8.71E−05
4.94E−02

Tsc22d3
5
0.84
0.565
0.772
1.41E−53
5.84E−49

Bcl2
5
0.863
0.694
0.658
9.92E−34
1.28E−29

Wdr89
5
0.996
0.97
0.291
1.59E−33
1.93E−29

Txnip
5
0.605
0.38
0.660
4.21E−27
3.45E−23

Ddit4
5
0.369
0.253
0.426
2.88E−20
1.53E−16

Zfp36l2
5
0.617
0.332
0.865
1.31E−19
6.44E−16

Il7r
5
0.48
0.286
0.612
2.61E−19
1.24E−15

Uba52
5
0.984
0.939
0.277
1.81E−18
7.96E−15

Pik3ip1
5
0.556
0.411
0.361
3.91E−13
9.67E−10

Cd74
5
0.501
0.562
−0.211
3.20E−11
6.20E−08

DynIl1
5
0.7
0.79
−0.370
4.66E−11
8.86E−08

Ifngr1
5
0.563
0.377
0.536
2.38E−10
4.10E−07

Jund
5
0.654
0.749
−0.319
1.15E−09
1.78E−06

Klhl6
5
0.332
0.208
0.485
2.58E−09
3.78E−06

Pdcd4
5
0.66
0.524
0.394
2.81E−09
4.09E−06

Lfng
5
0.333
0.379
−0.281
6.06E−09
8.46E−06

Ier2
5
0.428
0.464
−0.174
5.80E−08
6.87E−05

Ctsc
5
0.268
0.168
0.402
1.05E−07
1.17E−04

Dnaja1
5
0.591
0.71
−0.416
1.91E−07
2.05E−04

Ucp2
5
0.773
0.643
0.325
2.69E−07
2.79E−04

Tpm3
5
0.665
0.528
0.282
3.17E−07
3.25E−04

Igha
5
0.197
0.127
0.503
4.85E−07
4.77E−04

Tuba1a
5
0.302
0.345
−0.250
5.21E−07
5.08E−04

Dnajb1
5
0.206
0.351
−0.867
9.86E−07
9.09E−04

Dusp1
5
0.206
0.235
−0.321
3.53E−06
2.92E−03

Slc9a3r1
5
0.428
0.507
−0.256
5.20E−06
4.11E−03

Hspa8
5
0.977
0.975
−0.255
6.72E−06
5.15E−03

Sfpq
5
0.284
0.366
−0.373
6.74E−06
5.15E−03

Tdrp
5
0.228
0.277
−0.354
9.01E−06
6.69E−03

Ppp2ca
5
0.277
0.376
−0.469
1.12E−05
8.10E−03

Gramd3
5
0.475
0.302
0.481
1.65E−05
1.14E−02

Calm1
5
0.868
0.891
−0.192
1.69E−05
1.17E−02

Ppp3cc
5
0.152
0.074
0.621
1.87E−05
1.29E−02

Klf6
5
0.368
0.437
−0.374
2.48E−05
1.66E−02

1810037l17Rik
5
0.446
0.473
−0.158
2.48E−05
1.66E−02

Crlf3
5
0.569
0.421
0.370
3.69E−05
2.36E−02

Rnaset2a
5
0.709
0.583
0.225
4.18E−05
2.64E−02

Ppp1r15a
5
0.219
0.257
−0.287
4.73E−05
2.95E−02

Ltb
5
0.865
0.893
−0.238
5.43E−05
3.33E−02

Ilk
5
0.2
0.15
0.159
7.23E−05
4.22E−02

Racgap1
5
0.21
0.135
0.436
8.16E−05
4.70E−02

Mcpt1
6
0.35
0.058
0.479
8.41E−63
5.09E−58

Defa24
6
0.099
0.298
−1.145
2.72E−44
6.70E−40

Jund
6
0.92
0.964
−0.422
2.90E−43
6.92E−39

Igha
6
0.681
0.424
0.596
4.93E−39
7.92E−35

Mcpt2
6
0.212
0.03
0.749
2.04E−38
3.16E−34

Lyz1
6
0.035
0.174
−1.858
2.01E−37
2.99E−33

Ppia
6
0.998
0.998
0.186
9.41E−36
1.30E−31

Ddit4
6
0.221
0.077
1.322
7.53E−31
8.01E−27

Junb
6
0.745
0.856
−0.174
1.91E−30
2.01E−26

Fabp2
6
0.048
0.187
−1.495
4.37E−28
4.00E−24

Psap
6
0.997
0.999
0.202
6.20E−28
5.55E−24

Nr4a1
6
0.508
0.62
−0.422
8.34E−28
7.30E−24

Egr1
6
0.143
0.243
−0.987
2.00E−27
1.72E−23

Fosb
6
0.332
0.475
−0.556
3.19E−25
2.28E−21

Klf4
6
0.147
0.286
−0.763
1.96E−23
1.28E−19

Jun
6
0.769
0.66
0.499
9.00E−20
4.54E−16

Ptpre
6
0.392
0.534
−0.452
2.12E−19
1.02E−15

Neat1
6
0.885
0.81
0.364
1.57E−17
6.12E−14

Hist1h1c
6
0.522
0.364
0.792
2.52E−17
9.66E−14

Mir142hg
6
0.169
0.289
−0.649
6.19E−17
2.29E−13

Pnrc1
6
0.706
0.761
−0.212
2.17E−16
7.64E−13

Grasp
6
0.193
0.309
−0.617
2.21E−16
7.72E−13

Rilpl2
6
0.851
0.863
−0.158
3.71E−16
1.27E−12

Dusp5
6
0.668
0.711
−0.167
6.13E−16
2.02E−12

Kdm6b
6
0.307
0.397
−0.488
1.04E−15
3.34E−12

Bcl2l11
6
0.257
0.35
−0.499
2.99E−15
9.09E−12

Smc6
6
0.849
0.841
−0.180
1.25E−14
3.59E−11

Bhlhe40
6
0.465
0.543
−0.297
1.25E−14
3.59E−11

Ier2
6
0.432
0.538
−0.265
2.19E−14
6.02E−11

Dnajc7
6
0.987
0.976
0.197
6.20E−14
1.65E−10

Ier5
6
0.937
0.9
0.332
2.06E−13
5.27E−10

Hist2h4
6
0.165
0.066
1.036
3.04E−13
7.66E−10

Mpeg1
6
0.992
0.975
0.185
3.52E−13
8.76E−10

VgIl4
6
0.34
0.455
−0.419
4.36E−13
1.06E−09

Ifrd1
6
0.241
0.319
−0.459
4.97E−13
1.21E−09

Igkc
6
0.944
0.856
0.194
5.84E−13
1.40E−09

Ppp2ca
6
0.539
0.637
−0.356
6.35E−13
1.51E−09

Napsa
6
0.888
0.809
0.245
7.31E−13
1.73E−09

Klk1
6
0.964
0.956
0.243
8.31E−13
1.96E−09

Dusp18
6
0.091
0.161
−0.789
1.03E−12
2.35E−09

Rnase6
6
0.991
0.994
0.160
1.39E−12
3.13E−09

Filip1l
6
0.384
0.471
−0.295
2.43E−12
5.31E−09

Spsb2
6
0.187
0.275
−0.508
3.32E−12
7.11E−09

Vps37b
6
0.424
0.489
−0.292
6.60E−12
1.38E−08

Ccl4
6
0.848
0.889
0.241
7.42E−12
1.52E−08

Odc1
6
0.366
0.44
−0.325
9.58E−12
1.95E−08

Clec2d
6
0.578
0.438
0.409
1.12E−11
2.28E−08

H2-Ab1
6
0.949
0.947
0.238
1.36E−11
2.75E−08

Cxcr4
6
0.561
0.407
0.491
1.64E−11
3.26E−08

Pltp
6
0.878
0.806
0.260
1.78E−11
3.52E−08

D13Ertd608e
6
0.947
0.901
0.276
3.28E−11
6.34E−08

Dusp1
6
0.406
0.494
−0.366
3.41E−11
6.58E−08

Nr4a3
6
0.134
0.197
−0.556
4.12E−11
7.90E−08

Plek
6
0.617
0.652
−0.205
4.40E−11
8.40E−08

Fyn
6
0.756
0.799
−0.230
9.87E−11
1.83E−07

Rel
6
0.381
0.454
−0.305
1.01E−10
1.87E−07

Fam46c
6
0.221
0.306
−0.440
1.30E−10
2.35E−07

Wnk1
6
0.605
0.645
−0.262
1.60E−10
2.85E−07

Rpn2
6
0.664
0.569
0.272
1.79E−10
3.18E−07

H2-Aa
6
0.947
0.949
0.220
1.83E−10
3.24E−07

Pim1
6
0.509
0.58
−0.188
2.16E−10
3.77E−07

Rgs1
6
0.466
0.351
0.548
5.04E−10
8.21E−07

Pik3ip1
6
0.423
0.307
0.445
5.80E−10
9.38E−07

Runx3
6
0.53
0.603
−0.200
1.09E−09
1.70E−06

B3gnt8
6
0.486
0.362
0.265
1.17E−09
1.81E−06

Ppp1r16b
6
0.237
0.315
−0.419
1.41E−09
2.15E−06

Selplg
6
0.992
0.973
0.183
1.76E−09
2.67E−06

Atf3
6
0.091
0.161
−0.693
1.95E−09
2.92E−06

Npc2
6
0.985
0.975
0.166
2.14E−09
3.18E−06

Skil
6
0.435
0.477
−0.246
2.74E−09
4.01E−06

Traf4
6
0.535
0.592
−0.199
2.88E−09
4.19E−06

Emp3
6
0.936
0.856
0.172
4.65E−09
6.61E−06

Foxp1
6
0.719
0.741
−0.169
4.72E−09
6.68E−06

Ly6c1
6
0.991
0.99
−0.173
5.07E−09
7.14E−06

Zfp36l2
6
0.783
0.66
0.365
7.84E−09
1.06E−05

Ifi30
6
0.883
0.807
0.256
1.09E−08
1.45E−05

Zc3h12a
6
0.135
0.198
−0.495
1.43E−08
1.86E−05

Lag3
6
0.605
0.489
0.315
2.39E−08
3.01E−05

Plekho2
6
0.201
0.271
−0.406
2.76E−08
3.44E−05

S1pr4
6
0.351
0.27
0.331
3.95E−08
4.83E−05

Trim25
6
0.339
0.394
−0.239
4.20E−08
5.10E−05

Lgals1
6
0.985
0.97
0.174
4.90E−08
5.89E−05

Ptp4a1
6
0.4
0.412
−0.201
5.43E−08
6.48E−05

Erdr1
6
0.149
0.2
−0.520
5.84E−08
6.91E−05

Tgif1
6
0.115
0.174
−0.548
6.25E−08
7.30E−05

H2-Eb1
6
0.907
0.891
0.228
8.18E−08
9.36E−05

Clec10a
6
0.532
0.426
0.327
8.43E−08
9.63E−05

Gapdh
6
0.911
0.848
0.206
9.39E−08
1.06E−04

Gtf2i
6
0.542
0.484
0.283
9.52E−08
1.08E−04

Atp5h
6
0.963
0.92
0.168
9.81E−08
1.10E−04

Cd68
6
0.861
0.798
0.204
1.25E−07
1.38E−04

Itpkb
6
0.296
0.363
−0.230
1.78E−07
1.93E−04

Rnf19b
6
0.255
0.303
−0.314
1.88E−07
2.02E−04

Kmt2e
6
0.596
0.634
−0.156
1.91E−07
2.05E−04

Ddx3x
6
0.436
0.489
−0.202
2.38E−07
2.50E−04

Crem
6
0.34
0.38
−0.279
2.77E−07
2.87E−04

Zfand5
6
0.423
0.496
−0.220
3.13E−07
3.21E−04

Sell
6
0.983
0.962
0.172
3.31E−07
3.38E−04

Nfkbiz
6
0.336
0.381
−0.288
3.37E−07
3.42E−04

Coq10b
6
0.242
0.311
−0.336
3.65E−07
3.66E−04

Cd83
6
0.092
0.155
−0.472
3.80E−07
3.80E−04

Lmnb1
6
0.189
0.257
−0.415
4.02E−07
4.01E−04

Sla2
6
0.735
0.605
0.243
4.24E−07
4.23E−04

Cxcr3
6
0.516
0.405
0.302
4.51E−07
4.47E−04

Hes6
6
0.474
0.367
0.290
5.14E−07
5.04E−04

Sf3b1
6
0.706
0.627
0.237
5.35E−07
5.21E−04

Gnb1
6
0.515
0.574
−0.247
5.60E−07
5.41E−04

AY036118
6
0.426
0.414
−0.256
6.27E−07
6.02E−04

Siah2
6
0.253
0.318
−0.303
7.71E−07
7.24E−04

Fosl2
6
0.141
0.176
−0.387
9.82E−07
9.08E−04

Gapt
6
0.657
0.723
−0.204
1.23E−06
1.11E−03

Fkbp5
6
0.161
0.093
0.573
1.31E−06
1.18E−03

Cdv3
6
0.414
0.479
−0.219
1.33E−06
1.20E−03

Tnfaip8l2
6
0.512
0.419
0.307
1.42E−06
1.27E−03

Btg2
6
0.801
0.841
−0.156
1.51E−06
1.34E−03

Mcl1
6
0.459
0.495
−0.199
1.94E−06
1.71E−03

Socs3
6
0.55
0.49
0.385
2.68E−06
2.29E−03

Bloc1s2
6
0.784
0.694
0.218
2.78E−06
2.37E−03

Nfkbia
6
0.661
0.695
−0.191
2.85E−06
2.41E−03

Os9
6
0.441
0.365
0.265
2.87E−06
2.43E−03

Clcn3
6
0.35
0.383
−0.239
3.30E−06
2.76E−03

H2afj
6
0.935
0.878
0.166
3.66E−06
3.01E−03

Pink1
6
0.282
0.337
−0.291
4.12E−06
3.34E−03

Sema4b
6
0.531
0.453
0.221
4.49E−06
3.62E−03

Ablim1
6
0.403
0.451
−0.197
4.87E−06
3.87E−03

Rsrp1
6
0.754
0.701
0.195
5.54E−06
4.36E−03

Map3k1
6
0.346
0.397
−0.227
5.60E−06
4.39E−03

Ctsz
6
0.97
0.939
0.156
5.69E−06
4.45E−03

Gadd45b
6
0.342
0.413
−0.220
6.21E−06
4.80E−03

H2-DMa
6
0.878
0.801
0.190
6.66E−06
5.12E−03

Gnai2
6
0.932
0.939
−0.175
6.87E−06
5.24E−03

Irf4
6
0.256
0.304
−0.248
9.39E−06
6.95E−03

Ptprcap
6
0.941
0.894
0.159
1.09E−05
7.99E−03

Pten
6
0.429
0.475
−0.226
1.11E−05
8.01E−03

Tmem86a
6
0.204
0.151
0.323
1.21E−05
8.69E−03

Grb2
6
0.614
0.678
−0.222
1.23E−05
8.79E−03

Orai1
6
0.274
0.339
−0.245
1.48E−05
1.04E−02

Itgb7
6
0.669
0.574
0.238
1.65E−05
1.14E−02

Paqr5
6
0.52
0.453
0.279
1.81E−05
1.25E−02

Snrnp70
6
0.43
0.347
0.220
1.88E−05
1.29E−02

Sertad1
6
0.12
0.173
−0.396
1.94E−05
1.32E−02

Klf3
6
0.125
0.177
−0.428
2.01E−05
1.36E−02

Hnrnpa3
6
0.851
0.799
0.164
2.53E−05
1.69E−02

Tsix
6
0.23
0.271
−0.418
2.64E−05
1.75E−02

Cdkn2d
6
0.747
0.658
0.244
2.68E−05
1.77E−02

Rab7b
6
0.223
0.257
−0.285
3.09E−05
2.02E−02

Fcer1g
6
0.94
0.895
0.160
3.14E−05
2.05E−02

Tmem59
6
0.833
0.779
0.179
3.23E−05
2.10E−02

Klk1b27
6
0.974
0.955
0.170
3.69E−05
2.36E−02

Tmem50a
6
0.854
0.801
0.153
3.90E−05
2.48E−02

Txndc5
6
0.699
0.623
0.226
4.00E−05
2.54E−02

Lifr
6
0.595
0.489
0.265
4.03E−05
2.55E−02

Arid3a
6
0.212
0.247
−0.329
4.35E−05
2.74E−02

Pde4b
6
0.177
0.227
−0.282
4.84E−05
3.01E−02

Mark3
6
0.139
0.184
−0.383
4.92E−05
3.05E−02

Pdia3
6
0.844
0.792
0.157
5.00E−05
3.09E−02

Gatad1
6
0.34
0.391
−0.199
5.83E−05
3.53E−02

Arl4a
6
0.228
0.289
−0.276
6.07E−05
3.64E−02

Asph
6
0.377
0.405
−0.195
7.17E−05
4.20E−02

Net1
6
0.53
0.44
0.285
7.94E−05
4.59E−02

Cfp
6
0.422
0.358
0.312
8.22E−05
4.72E−02

5730508B09Rik
6
0.268
0.313
−0.218
8.68E−05
4.94E−02

Zfp36l2
7
0.757
0.354
1.239
4.40E−35
5.97E−31

Tsc22d3
7
0.565
0.294
1.003
1.83E−19
8.83E−16

Ddit4
7
0.359
0.273
0.463
2.18E−14
5.99E−11

Lmo4
7
0.204
0.135
0.711
1.35E−10
2.43E−07

Dusp2
7
0.465
0.327
0.542
4.00E−09
5.74E−06

Txnip
7
0.415
0.275
0.551
7.43E−09
1.01E−05

Ptpn22
7
0.53
0.429
0.340
3.19E−06
2.67E−03

Fkbp5
7
0.167
0.091
0.540
4.79E−06
3.82E−03

Il7r
7
0.191
0.123
0.526
7.22E−06
5.48E−03

Hsp90ab1
7
0.834
0.891
−0.450
7.82E−06
5.88E−03

Matk
7
0.284
0.173
0.513
3.61E−05
2.32E−02

Gabarapl2
7
0.643
0.554
0.253
6.23E−05
3.72E−02

Svbp
7
0.246
0.178
0.261
7.76E−05
4.50E−02

Jund
8
0.846
0.905
−0.703
1.54E−45
4.48E−41

Txnip
8
0.398
0.146
1.190
8.77E−36
1.23E−31

Kdm6b
8
0.274
0.451
−0.833
9.22E−28
7.97E−24

Nfkbia
8
0.614
0.778
−0.579
6.04E−27
4.90E−23

Crem
8
0.371
0.502
−0.681
1.50E−23
9.85E−20

Mcpt1
8
0.209
0.037
1.756
5.20E−23
3.28E−19

Nfkbid
8
0.146
0.323
−1.010
7.52E−23
4.70E−19

Ifrd1
8
0.276
0.434
−0.708
7.62E−22
4.41E−18

Defa24
8
0.044
0.172
−0.967
8.62E−22
4.95E−18

Nr4a1
8
0.561
0.698
−0.415
3.63E−21
2.02E−17

Nfkbiz
8
0.358
0.471
−0.640
1.02E−19
5.07E−16

Litaf
8
0.339
0.488
−0.518
1.52E−18
6.74E−15

Rgs1
8
0.699
0.507
0.795
2.13E−18
9.31E−15

Nr4a3
8
0.157
0.272
−0.808
5.15E−18
2.18E−14

Gadd45b
8
0.17
0.326
−0.563
8.88E−18
3.60E−14

Ier5l
8
0.057
0.16
−1.422
4.06E−17
1.54E−13

H3f3b
8
0.993
0.996
−0.185
5.58E−17
2.08E−13

AW112010
8
0.995
0.996
0.208
2.63E−16
9.12E−13

Id2
8
0.684
0.497
0.467
2.67E−16
9.22E−13

Ncr1
8
0.964
0.931
0.265
4.30E−16
1.45E−12

Lmna
8
0.089
0.207
−1.022
1.00E−15
3.23E−12

Nr4a2
8
0.348
0.486
−0.530
1.28E−15
4.07E−12

Prr7
8
0.093
0.208
−0.910
2.04E−15
6.31E−12

VgIl4
8
0.47
0.602
−0.452
2.25E−15
6.92E−12

Tsc22d3
8
0.664
0.475
0.472
3.58E−15
1.07E−11

Tgif1
8
0.305
0.437
−0.580
4.29E−15
1.28E−11

Cd74
8
0.448
0.563
−0.187
5.48E−15
1.60E−11

Hist1h1e
8
0.176
0.047
1.277
1.14E−14
3.28E−11

Nkg7
8
0.985
0.981
0.194
6.12E−14
1.63E−10

Gzma
8
0.764
0.719
0.340
9.80E−14
2.57E−10

AY036118
8
0.431
0.444
−0.339
1.27E−13
3.31E−10

Mir142hg
8
0.161
0.29
−0.715
2.41E−13
6.14E−10

Zfp36l2
8
0.84
0.66
0.382
4.30E−13
1.05E−09

Traf1
8
0.464
0.552
−0.355
4.30E−13
1.05E−09

Cxcr4
8
0.577
0.349
0.544
5.87E−13
1.40E−09

Egr1
8
0.156
0.256
−0.640
5.89E−13
1.40E−09

Zc3h12a
8
0.182
0.288
−0.680
1.19E−12
2.71E−09

Klrc1
8
0.608
0.463
0.392
2.12E−12
4.69E−09

Klrb1f
8
0.56
0.394
0.487
2.48E−12
5.40E−09

Cdkn1a
8
0.084
0.191
−0.980
2.74E−12
5.93E−09

Ftl1
8
0.963
0.977
−0.171
4.25E−12
9.04E−09

Fosl2
8
0.378
0.418
−0.358
6.97E−12
1.44E−08

Icam1
8
0.175
0.304
−0.819
7.07E−12
1.46E−08

Pnrc1
8
0.769
0.836
−0.302
8.05E−12
1.65E−08

Odc1
8
0.202
0.284
−0.540
1.51E−11
3.04E−08

Pim1
8
0.677
0.77
−0.358
2.02E−11
3.95E−08

Igha
8
0.488
0.302
0.514
6.38E−11
1.21E−07

Emb
8
0.506
0.54
−0.223
9.10E−11
1.69E−07

Zfp512
8
0.446
0.273
0.523
1.36E−10
2.44E−07

Hist1h1c
8
0.348
0.217
0.586
2.05E−10
3.61E−07

Ptprcap
8
0.929
0.844
0.276
2.51E−10
4.30E−07

Vps37b
8
0.79
0.825
−0.178
2.53E−10
4.33E−07

Rel
8
0.139
0.222
−0.595
2.67E−10
4.54E−07

Gramd3
8
0.227
0.338
−0.502
3.02E−10
5.06E−07

Klre1
8
0.744
0.645
0.295
4.38E−10
7.22E−07

Ms4a6b
8
0.419
0.257
0.490
5.22E−10
8.47E−07

Igkc
8
0.677
0.522
0.390
8.49E−10
1.35E−06

Klrd1
8
0.939
0.866
0.261
1.17E−09
1.81E−06

H2-K1
8
0.978
0.991
0.192
1.37E−09
2.10E−06

Ikzf2
8
0.216
0.283
−0.467
1.82E−09
2.74E−06

Ptp4a2
8
0.606
0.7
−0.243
2.08E−09
3.11E−06

Ms4a4b
8
0.953
0.903
0.271
2.28E−09
3.39E−06

Rrad
8
0.191
0.264
−0.602
3.81E−09
5.49E−06

Maff
8
0.251
0.326
−0.445
6.29E−09
8.76E−06

Coq10b
8
0.305
0.401
−0.426
1.31E−08
1.72E−05

Tfam
8
0.19
0.248
−0.555
1.44E−08
1.87E−05

Phlda1
8
0.134
0.234
−0.867
1.86E−08
2.38E−05

Klrc2
8
0.505
0.376
0.396
1.92E−08
2.45E−05

B2m
8
0.999
0.997
0.159
2.10E−08
2.66E−05

Fcer1g
8
0.927
0.913
0.170
3.13E−08
3.88E−05

Arl6ip5
8
0.618
0.461
0.344
3.31E−08
4.08E−05

Gimap9
8
0.511
0.364
0.367
3.43E−08
4.23E−05

Ddx21
8
0.248
0.322
−0.379
4.05E−08
4.94E−05

Ifi203
8
0.547
0.387
0.402
4.11E−08
5.01E−05

Arl6ip1
8
0.61
0.447
0.367
4.47E−08
5.40E−05

Eif4a2
8
0.622
0.453
0.300
6.14E−08
7.21E−05

Myl6
8
0.987
0.955
0.199
7.12E−08
8.23E−05

Ier2
8
0.781
0.851
−0.235
9.00E−08
1.02E−04

Eef2
8
0.957
0.896
0.257
1.06E−07
1.19E−04

Txndc5
8
0.239
0.137
0.592
1.21E−07
1.34E−04

Gimap1
8
0.776
0.641
0.283
1.45E−07
1.59E−04

Klrb1c
8
0.735
0.621
0.233
1.78E−07
1.93E−04

Actr3
8
0.771
0.639
0.315
2.06E−07
2.20E−04

Gnai2
8
0.661
0.685
−0.261
2.16E−07
2.30E−04

Ppp1r16b
8
0.206
0.28
−0.367
2.26E−07
2.39E−04

Fasl
8
0.598
0.488
0.296
2.30E−07
2.42E−04

Ube2s
8
0.478
0.535
−0.248
2.30E−07
2.42E−04

Ppp1r15a
8
0.406
0.499
−0.355
2.52E−07
2.63E−04

Gimap6
8
0.815
0.682
0.272
3.06E−07
3.15E−04

Amd1
8
0.265
0.34
−0.426
3.32E−07
3.38E−04

Dusp1
8
0.614
0.702
−0.244
4.56E−07
4.51E−04

Sh2d1a
8
0.488
0.367
0.388
6.06E−07
5.83E−04

Nfkb1
8
0.374
0.425
−0.244
6.15E−07
5.91E−04

Fam105a
8
0.376
0.26
0.376
7.53E−07
7.10E−04

Bcl2
8
0.839
0.743
0.286
7.94E−07
7.43E−04

Alyref
8
0.137
0.207
−0.597
8.08E−07
7.55E−04

Arfrp1
8
0.21
0.119
0.609
8.64E−07
8.02E−04

Taf10
8
0.347
0.414
−0.372
9.27E−07
8.59E−04

Sik1
8
0.161
0.229
−0.527
1.00E−06
9.23E−04

Cdk2ap1
8
0.132
0.215
−0.673
1.04E−06
9.53E−04

Rac2
8
0.97
0.949
0.169
1.22E−06
1.11E−03

Ctla2a
8
0.74
0.637
0.372
1.39E−06
1.25E−03

Skil
8
0.207
0.271
−0.410
1.77E−06
1.56E−03

Ccr2
8
0.536
0.39
0.330
2.01E−06
1.76E−03

Sla
8
0.335
0.218
0.486
2.10E−06
1.83E−03

Cd47
8
0.833
0.739
0.262
2.56E−06
2.20E−03

Dgat1
8
0.175
0.229
−0.352
2.67E−06
2.29E−03

Tm6sf1
8
0.454
0.334
0.360
2.71E−06
2.31E−03

Gramd1a
8
0.336
0.214
0.460
3.06E−06
2.57E−03

Il2rg
8
0.681
0.727
−0.226
3.62E−06
2.98E−03

Sp100
8
0.537
0.411
0.330
3.65E−06
3.00E−03

Ninj1
8
0.125
0.168
−0.512
3.92E−06
3.19E−03

Klrk1
8
0.873
0.763
0.213
4.14E−06
3.36E−03

Rnf125
8
0.167
0.241
−0.483
4.94E−06
3.91E−03

Bcl2l11
8
0.383
0.425
−0.208
5.91E−06
4.60E−03

Neurl3
8
0.388
0.429
−0.244
6.01E−06
4.67E−03

Rora
8
0.161
0.227
−0.455
6.55E−06
5.05E−03

Nabp1
8
0.702
0.683
−0.167
8.55E−06
6.38E−03

Csrp1
8
0.129
0.179
−0.437
1.12E−05
8.10E−03

Cks2
8
0.108
0.156
−0.601
1.12E−05
8.10E−03

Rnf157
8
0.188
0.24
−0.362
1.20E−05
8.62E−03

Arpc5l
8
0.381
0.254
0.383
2.08E−05
1.40E−02

Slfn2
8
0.408
0.3
0.342
2.15E−05
1.45E−02

Bcl2a1b
8
0.151
0.215
−0.507
2.23E−05
1.50E−02

Rsrp1
8
0.559
0.436
0.318
2.24E−05
1.50E−02

Il16
8
0.336
0.223
0.455
2.52E−05
1.68E−02

Arf4
8
0.478
0.495
−0.186
2.66E−05
1.76E−02

Rab35
8
0.207
0.123
0.478
2.81E−05
1.85E−02

Kdm2b
8
0.158
0.203
−0.379
3.08E−05
2.01E−02

Ndel1
8
0.216
0.281
−0.337
3.09E−05
2.02E−02

Ppp3cc
8
0.268
0.156
0.528
3.78E−05
2.41E−02

Cdv3
8
0.255
0.294
−0.281
4.42E−05
2.77E−02

Nfkbie
8
0.111
0.158
−0.483
4.49E−05
2.82E−02

Klf6
8
0.589
0.544
0.166
4.89E−05
3.04E−02

Neat1
8
0.503
0.415
0.275
5.11E−05
3.15E−02

Samd9l
8
0.176
0.106
0.479
5.18E−05
3.19E−02

Arrb2
8
0.32
0.246
0.295
5.19E−05
3.19E−02

Jun
8
0.453
0.384
0.210
5.29E−05
3.25E−02

P2ry10
8
0.374
0.396
−0.196
5.34E−05
3.27E−02

Nfil3
8
0.365
0.244
0.490
5.82E−05
3.53E−02

Ash1l
8
0.235
0.139
0.491
5.93E−05
3.57E−02

Hcst
8
0.898
0.809
0.174
6.28E−05
3.75E−02

Klf4
8
0.122
0.175
−0.524
6.42E−05
3.82E−02

Cap1
8
0.695
0.601
0.235
6.52E−05
3.86E−02

Bhlhe40
8
0.571
0.62
−0.159
6.54E−05
3.87E−02

Lax1
8
0.286
0.18
0.486
7.05E−05
4.14E−02

Clec2d
8
0.289
0.194
0.391
7.08E−05
4.15E−02

Cd69
8
0.306
0.357
−0.386
7.60E−05
4.42E−02

Samsn1
8
0.324
0.369
−0.280
8.02E−05
4.63E−02

Tuba4a
8
0.191
0.222
−0.361
8.56E−05
4.89E−02

Igha
9
0.566
0.317
0.227
2.42E−50
9.06E−46

Ighg3
9
0.211
0.027
1.831
5.18E−28
4.69E−24

Wdr89
9
0.993
0.989
0.469
4.18E−24
2.84E−20

Zfp36l2
9
0.758
0.305
1.590
8.84E−23
5.48E−19

Mcpt1
9
0.156
0.003
2.708
2.58E−21
1.46E−17

Uba52
9
0.996
0.992
0.365
9.80E−13
2.26E−09

Hspa8
9
0.995
0.998
−0.426
4.24E−12
9.04E−09

Rsrp1
9
0.796
0.802
−0.274
1.03E−10
1.91E−07

Tsc22d3
9
0.669
0.347
1.031
2.68E−10
4.54E−07

Ddit4
9
0.241
0.105
0.791
7.45E−09
1.01E−05

Nme2
9
0.4
0.228
0.703
1.33E−08
1.75E−05

Serinc3
9
0.874
0.576
0.784
4.83E−08
5.82E−05

Ubb
9
0.998
1
−0.190
4.77E−07
4.71E−04

Basp1
9
0.871
0.947
−0.559
1.11E−06
1.01E−03

Il2
9
0.244
0.092
0.918
2.19E−06
1.90E−03

Cdk1
9
0.478
0.555
−0.396
3.14E−06
2.63E−03

Cks1brt
9
0.262
0.111
1.033
3.83E−06
3.13E−03

Actg1
9
1
1
−0.161
3.88E−06
3.16E−03

Tubb5
9
0.966
0.973
−0.244
4.06E−06
3.30E−03

Malat1
9
1
0.998
−0.269
4.52E−06
3.64E−03

Lnx2
9
0.191
0.075
0.811
8.25E−06
6.18E−03

Narf
9
0.441
0.28
0.449
1.29E−05
9.17E−03

Apobec1
9
0.86
0.753
0.201
3.28E−05
2.13E−02

AC125149.3
9
0.619
0.477
0.342
5.12E−05
3.16E−02

Eif2ak3
9
0.384
0.189
0.581
7.28E−05
4.25E−02

Zfp36l2
10
0.68
0.182
1.856
5.31E−26
4.02E−22

Igha
10
0.405
0.229
0.162
2.16E−16
7.61E−13

Tsc22d3
10
0.689
0.322
1.088
2.41E−14
6.57E−11

Ttc7
10
0.244
0.061
1.338
4.72E−12
9.91E−09

Sesn1
10
0.402
0.141
1.071
7.32E−11
1.37E−07

1110059E24Rik
10
0.507
0.266
0.715
2.47E−10
4.25E−07

Apobec1
10
0.807
0.618
0.309
1.04E−07
1.17E−04

Ddit4
10
0.296
0.126
0.864
2.21E−07
2.34E−04

Uba52
10
0.985
0.948
0.287
2.96E−07
3.05E−04

Rsrp1
10
0.722
0.702
−0.187
7.68E−07
7.23E−04

Hspa8
10
0.975
0.984
−0.286
3.38E−06
2.80E−03

Dusp1
10
0.451
0.253
0.614
3.45E−06
2.85E−03

Napsa
10
0.776
0.644
0.374
4.92E−06
3.90E−03

Cd47
10
0.602
0.368
0.638
6.15E−06
4.76E−03

Egln2
10
0.558
0.321
0.624
7.51E−06
5.69E−03

Btg1
10
0.985
0.95
0.438
1.03E−05
7.53E−03

Serinc3
10
0.764
0.397
0.883
1.09E−05
7.93E−03

Ppp1r21
10
0.165
0.052
1.045
1.38E−05
9.74E−03

Crlf3
10
0.658
0.479
0.396
2.36E−05
1.59E−02

Basp1
10
0.755
0.852
−0.516
3.20E−05
2.08E−02

Sh3glb2
10
0.187
0.134
0.383
6.45E−05
3.83E−02

Jund
11
0.855
0.944
−0.624
3.24E−34
4.33E−30

Id2
11
0.879
0.641
0.666
6.36E−27
5.11E−23

Egr1
11
0.191
0.33
−1.192
1.14E−17
4.52E−14

Fabp2
11
0.021
0.151
−2.142
3.09E−17
1.18E−13

AY036118
11
0.447
0.432
−0.357
5.25E−17
1.98E−13

Crem
11
0.344
0.551
−0.785
7.48E−17
2.75E−13

Nr4a1
11
0.625
0.775
−0.424
7.83E−17
2.87E−13

Junb
11
0.938
0.981
−0.194
2.59E−16
9.03E−13

Nr4a3
11
0.195
0.378
−0.968
8.68E−16
2.84E−12

Mcpt1
11
0.217
0.041
1.668
1.94E−14
5.45E−11

Pim1
11
0.799
0.92
−0.269
2.06E−14
5.72E−11

Txnip
11
0.434
0.21
0.976
2.08E−14
5.75E−11

Kdm6b
11
0.346
0.499
−0.703
4.22E−14
1.14E−10

Litaf
11
0.387
0.553
−0.562
5.84E−13
1.40E−09

Tgif1
11
0.408
0.575
−0.505
8.44E−13
1.98E−09

Vps37b
11
0.732
0.829
−0.394
1.30E−12
2.95E−09

Ier5l
11
0.047
0.162
−1.609
1.53E−12
3.43E−09

Rel
11
0.195
0.361
−0.837
2.10E−12
4.67E−09

Zfp36l2
11
0.803
0.6
0.464
2.16E−12
4.76E−09

Nr4a2
11
0.236
0.4
−0.777
3.96E−12
8.47E−09

Lmna
11
0.074
0.19
−1.198
4.31E−12
9.15E−09

Nfkbid
11
0.287
0.46
−0.759
4.43E−12
9.36E−09

Ier2
11
0.707
0.814
−0.331
4.56E−12
9.60E−09

Traf1
11
0.57
0.698
−0.462
5.06E−12
1.06E−08

Defa24
11
0.035
0.16
−1.545
1.58E−11
3.17E−08

Phlda1
11
0.205
0.376
−0.883
1.59E−11
3.18E−08

Rgs1
11
0.857
0.711
0.486
2.93E−11
5.70E−08

Nfkb1
11
0.301
0.419
−0.649
3.42E−11
6.58E−08

Igkc
11
0.691
0.508
0.474
3.59E−11
6.90E−08

Klrc1
11
0.676
0.505
0.477
8.20E−11
1.53E−07

Tpm4
11
0.453
0.583
−0.477
1.04E−10
1.91E−07

Fam110a
11
0.105
0.22
−0.925
2.58E−10
4.40E−07

Fosl2
11
0.35
0.492
−0.566
3.03E−10
5.08E−07

Nfkbiz
11
0.545
0.665
−0.342
5.04E−10
8.21E−07

Irf8
11
0.447
0.553
−0.411
6.67E−10
1.07E−06

Maff
11
0.404
0.562
−0.400
7.21E−10
1.16E−06

Rora
11
0.5
0.603
−0.466
8.69E−10
1.38E−06

Sla
11
0.498
0.274
0.612
1.41E−09
2.15E−06

Ifrd1
11
0.32
0.458
−0.514
2.53E−09
3.72E−06

Klrb1f
11
0.656
0.495
0.457
9.35E−09
1.25E−05

Gadd45b
11
0.447
0.598
−0.389
1.26E−08
1.65E−05

Ikzf2
11
0.721
0.801
−0.383
1.39E−08
1.82E−05

Bcl2a1d
11
0.607
0.683
−0.405
1.45E−08
1.88E−05

Hist1h1c
11
0.402
0.21
0.662
1.81E−08
2.32E−05

Bcl2
11
0.916
0.814
0.380
1.82E−08
2.33E−05

Tsc22d3
11
0.582
0.393
0.564
1.97E−08
2.51E−05

Ptp4a2
11
0.652
0.739
−0.322
2.31E−08
2.92E−05

Nfkbia
11
0.82
0.892
−0.211
2.33E−08
2.95E−05

Dusp5
11
0.691
0.771
−0.198
3.02E−08
3.76E−05

Bcl2a1b
11
0.518
0.6
−0.492
5.15E−08
6.17E−05

Sik1
11
0.146
0.231
−0.679
6.10E−08
7.18E−05

Il7r
11
0.824
0.734
0.359
7.33E−08
8.43E−05

Nabp1
11
0.754
0.771
−0.335
7.69E−08
8.82E−05

Cd74
11
0.498
0.581
−0.289
1.12E−07
1.24E−04

Btg2
11
0.947
0.976
−0.166
1.57E−07
1.72E−04

Sub1
11
0.898
0.94
−0.239
2.03E−07
2.17E−04

Coq10b
11
0.287
0.406
−0.527
2.42E−07
2.54E−04

Pnrc1
11
0.826
0.89
−0.214
2.63E−07
2.74E−04

Skil
11
0.166
0.281
−0.626
3.25E−07
3.32E−04

Samsn1
11
0.455
0.54
−0.404
3.54E−07
3.57E−04

Ltb
11
0.975
0.946
0.288
4.72E−07
4.66E−04

Ubb
11
0.998
1
−0.186
5.50E−07
5.34E−04

Ahr
11
0.395
0.248
0.630
5.85E−07
5.64E−04

Mir142hg
11
0.148
0.253
−0.656
6.33E−07
6.07E−04

Map3k14
11
0.141
0.24
−0.737
8.20E−07
7.65E−04

Cited4
11
0.512
0.346
0.292
9.52E−07
8.81E−04

Gimap9
11
0.5
0.354
0.467
3.22E−06
2.69E−03

Gimap6
11
0.854
0.749
0.279
3.36E−06
2.79E−03

Gimap7
11
0.719
0.59
0.349
3.56E−06
2.94E−03

Dok1
11
0.215
0.102
0.756
3.75E−06
3.07E−03

B2m
11
0.998
1
0.156
4.36E−06
3.54E−03

Zc3h12a
11
0.246
0.363
−0.506
4.37E−06
3.54E−03

AW112010
11
1
0.994
0.167
5.49E−06
4.32E−03

Igha
11
0.461
0.283
0.479
5.99E−06
4.66E−03

Gnb1
11
0.32
0.419
−0.404
7.40E−06
5.61E−03

Hexim1
11
0.09
0.175
−0.822
7.63E−06
5.75E−03

Gimap3
11
0.941
0.914
0.224
7.97E−06
5.98E−03

Rhog
11
0.213
0.313
−0.491
1.00E−05
7.37E−03

Bhlhe40
11
0.623
0.693
−0.227
1.05E−05
7.66E−03

Tmem176a
11
0.701
0.536
0.383
1.47E−05
1.03E−02

Tsix
11
0.133
0.201
−0.615
1.53E−05
1.07E−02

VgIl4
11
0.387
0.479
−0.446
1.82E−05
1.25E−02

Gimap1
11
0.754
0.652
0.275
2.92E−05
1.91E−02

Gna13
11
0.371
0.449
−0.345
3.23E−05
2.10E−02

Cd69
11
0.496
0.598
−0.200
3.41E−05
2.20E−02

Amd1
11
0.174
0.238
−0.549
3.57E−05
2.29E−02

Ngrn
11
0.168
0.067
0.921
4.08E−05
2.58E−02

Bud31
11
0.291
0.367
−0.400
4.56E−05
2.85E−02

Ubc
11
0.369
0.464
−0.354
4.82E−05
3.01E−02

Gimap5
11
0.672
0.529
0.360
4.84E−05
3.01E−02

9930111J21Rik2
11
0.217
0.106
0.791
4.94E−05
3.06E−02

Icam1
11
0.281
0.38
−0.441
5.73E−05
3.49E−02

Mxd1
11
0.523
0.611
−0.273
6.08E−05
3.64E−02

Asb2
11
0.441
0.294
0.482
6.95E−05
4.09E−02

Eif4a1
11
0.727
0.754
−0.192
7.81E−05
4.52E−02

Anapc16
11
0.195
0.097
0.702
8.29E−05
4.76E−02

Srgn
12
0.99
0.876
0.838
6.70E−42
1.39E−37

Il13
12
0.614
0.233
2.088
1.02E−33
1.30E−29

Plk3
12
0.419
0.066
2.118
5.52E−29
5.24E−25

Sla
12
0.73
0.342
1.237
2.30E−25
1.66E−21

Zfp36l1
12
0.984
0.922
0.569
4.00E−24
2.74E−20

Jund
12
0.888
0.949
−0.733
1.05E−23
6.98E−20

Hspa8
12
0.974
0.894
0.424
2.23E−22
1.36E−18

Il4
12
0.701
0.352
1.591
3.24E−22
1.93E−18

Cxcr6
12
0.884
0.684
0.732
1.40E−21
7.98E−18

Furin
12
0.789
0.504
1.089
4.44E−21
2.44E−17

Ier2
12
0.785
0.823
−0.913
1.29E−20
6.96E−17

Pim3
12
0.551
0.241
1.184
4.81E−20
2.54E−16

Nab2
12
0.309
0.046
2.136
1.70E−19
8.27E−16

Areg
12
0.589
0.271
1.194
3.57E−18
1.54E−14

Rel
12
0.476
0.185
1.320
9.56E−18
3.86E−14

Ubb
12
0.984
0.967
−0.307
1.83E−17
7.06E−14

Egr1
12
0.449
0.489
−0.834
3.18E−16
1.09E−12

Fos
12
0.797
0.868
−0.975
4.46E−16
1.49E−12

Zap70
12
0.604
0.281
0.945
5.90E−16
1.95E−12

Rheb
12
0.738
0.458
0.668
9.15E−16
2.98E−12

Dusp1
12
0.734
0.825
−0.671
1.04E−15
3.33E−12

Cytip
12
0.858
0.572
0.629
2.35E−15
7.19E−12

Lif
12
0.348
0.099
1.263
2.71E−15
8.28E−12

Lmna
12
0.085
0.253
−1.359
8.70E−15
2.53E−11

Hilpda
12
0.921
0.785
0.484
1.55E−13
3.99E−10

Cycs
12
0.695
0.42
0.799
2.60E−13
6.60E−10

Sptssa
12
0.898
0.909
−0.295
2.64E−13
6.69E−10

Nxpe3
12
0.307
0.076
1.364
2.71E−13
6.83E−10

Mcpt1
12
0.242
0.048
1.458
3.95E−13
9.74E−10

Prr7
12
0.118
0.263
−1.304
8.63E−13
2.01E−09

Pdcd1
12
0.443
0.147
1.179
1.90E−12
4.22E−09

Fabp2
12
0.024
0.157
−2.073
5.42E−12
1.13E−08

Rap1b
12
0.76
0.524
0.609
1.52E−11
3.05E−08

Klf2
12
0.394
0.509
−1.024
2.39E−11
4.67E−08

Gadd45b
12
0.807
0.58
0.474
8.59E−11
1.60E−07

Nrgn
12
0.427
0.18
1.027
1.20E−10
2.18E−07

Adora2a
12
0.398
0.162
1.022
1.20E−10
2.18E−07

Plaur
12
0.447
0.175
1.074
1.32E−10
2.38E−07

Spty2d1
12
0.713
0.499
0.568
1.86E−10
3.28E−07

Nr4a2
12
0.526
0.294
0.760
2.58E−10
4.40E−07

Ccl1
12
0.285
0.101
1.634
2.93E−10
4.95E−07

Kif23
12
0.138
0.268
−1.060
2.98E−10
5.01E−07

Cd27
12
0.693
0.468
0.632
4.81E−10
7.88E−07

Lgals7
12
0.215
0.051
1.450
7.68E−10
1.23E−06

Gypc
12
0.358
0.142
0.911
8.21E−10
1.31E−06

Bcl2
12
0.791
0.625
0.473
9.98E−10
1.57E−06

Slc3a2
12
0.72
0.468
0.577
1.64E−09
2.49E−06

Cisd2
12
0.638
0.337
0.655
1.85E−09
2.78E−06

Abi3
12
0.159
0.294
−0.824
2.43E−09
3.59E−06

Defa24
12
0.061
0.182
−1.210
2.49E−09
3.66E−06

Cotl1
12
0.774
0.775
−0.219
4.37E−09
6.24E−06

Tnfaip8
12
0.638
0.385
0.663
4.69E−09
6.64E−06

Gata3
12
0.982
0.901
0.334
5.32E−09
7.47E−06

Clk1
12
0.427
0.542
−0.574
5.66E−09
7.93E−06

Dnaja1
12
0.904
0.901
−0.457
6.32E−09
8.79E−06

Ccr4
12
0.407
0.177
0.845
6.35E−09
8.82E−06

Nfkb1
12
0.884
0.772
0.412
6.68E−09
9.22E−06

Klf6
12
0.441
0.557
−0.873
6.76E−09
9.31E−06

Tgfb1
12
0.618
0.405
0.679
8.22E−09
1.11E−05

Lilrb4a
12
0.313
0.127
1.020
1.05E−08
1.40E−05

Mmd
12
0.28
0.076
1.490
1.41E−08
1.84E−05

Ifngr2
12
0.376
0.167
0.916
1.46E−08
1.89E−05

Id2
12
0.878
0.724
0.583
1.99E−08
2.53E−05

Prdx6
12
0.726
0.506
0.666
2.46E−08
3.09E−05

Serpina3g
12
0.467
0.294
1.116
2.51E−08
3.14E−05

Trf
12
0.222
0.066
1.243
4.52E−08
5.46E−05

Rassf5
12
0.455
0.205
0.796
4.94E−08
5.93E−05

Gch1
12
0.157
0.028
1.674
5.78E−08
6.87E−05

Gpcpd1
12
0.254
0.38
−0.513
5.86E−08
6.91E−05

Cited2
12
0.325
0.486
−0.576
6.19E−08
7.26E−05

Crem
12
0.713
0.484
0.281
6.98E−08
8.08E−05

Dtx1
12
0.268
0.408
−0.557
7.14E−08
8.24E−05

Gimap5
12
0.553
0.322
0.704
9.51E−08
1.08E−04

Eef2
12
0.982
0.942
0.321
1.01E−07
1.14E−04

Abhd17c
12
0.465
0.248
0.667
1.02E−07
1.15E−04

Nfkbiz
12
0.874
0.737
0.340
1.04E−07
1.17E−04

Tagln2
12
0.74
0.709
−0.161
1.22E−07
1.35E−04

Sh2d2a
12
0.533
0.271
0.767
1.33E−07
1.46E−04

Egr2
12
0.157
0.03
1.855
1.65E−07
1.80E−04

Fosl2
12
0.677
0.456
0.481
1.73E−07
1.88E−04

Ppp1r15a
12
0.654
0.709
−0.415
2.01E−07
2.15E−04

Selplg
12
0.862
0.706
0.461
2.20E−07
2.34E−04

Atp2b1
12
0.524
0.311
0.573
2.69E−07
2.80E−04

Eif4a1
12
0.911
0.775
0.421
2.98E−07
3.07E−04

Rhob
12
0.234
0.322
−0.776
3.43E−07
3.47E−04

Scp2
12
0.65
0.646
−0.199
3.49E−07
3.52E−04

Rap1a
12
0.553
0.319
0.726
3.78E−07
3.79E−04

Zfp36
12
0.514
0.491
−0.561
4.30E−07
4.28E−04

Hic1
12
0.356
0.144
0.964
5.04E−07
4.94E−04

Tpm4
12
0.551
0.329
0.654
5.60E−07
5.41E−04

Esm1
12
0.093
0.233
−0.997
6.47E−07
6.18E−04

Kcnn4
12
0.234
0.309
−0.527
7.30E−07
6.91E−04

Orai1
12
0.459
0.238
0.758
1.01E−06
9.32E−04

Ubc
12
0.404
0.489
−0.472
1.04E−06
9.54E−04

Txnip
12
0.114
0.218
−1.091
1.05E−06
9.57E−04

Fosb
12
0.472
0.496
−0.561
1.54E−06
1.37E−03

Cntnap2
12
0.083
0.187
−1.029
1.99E−06
1.75E−03

Nab1
12
0.246
0.084
1.142
2.04E−06
1.78E−03

Traf4
12
0.301
0.162
0.878
2.66E−06
2.28E−03

AY036118
12
0.429
0.438
−0.381
2.85E−06
2.41E−03

Igkc
12
0.734
0.547
0.321
3.30E−06
2.76E−03

Tsc22d3
12
0.333
0.375
−0.528
3.31E−06
2.76E−03

Rasa2
12
0.354
0.162
0.780
3.32E−06
2.77E−03

Igha
12
0.516
0.316
0.508
3.35E−06
2.78E−03

Nr4a3
12
0.559
0.37
0.596
3.41E−06
2.82E−03

Sub1
12
0.978
0.919
0.258
3.46E−06
2.86E−03

Jun
12
0.616
0.689
−0.758
3.79E−06
3.10E−03

DynIl1
12
0.691
0.499
0.524
3.80E−06
3.11E−03

Il2ra
12
0.604
0.382
0.561
4.84E−06
3.85E−03

Ramp1
12
0.417
0.435
−0.296
5.11E−06
4.04E−03

Mapkapk2
12
0.211
0.066
1.193
5.83E−06
4.55E−03

Slc2a3
12
0.157
0.043
1.265
6.66E−06
5.12E−03

Btg3
12
0.266
0.104
0.862
6.70E−06
5.14E−03

Arl5c
12
0.179
0.271
−0.886
7.34E−06
5.57E−03

Lilr4b
12
0.274
0.111
0.886
7.85E−06
5.90E−03

Ndfip1
12
0.417
0.241
0.606
9.38E−06
6.95E−03

Ptpn22
12
0.451
0.271
0.629
9.54E−06
7.05E−03

Tmem59
12
0.65
0.623
−0.162
1.10E−05
8.01E−03

Pnrc1
12
0.768
0.787
−0.254
1.11E−05
8.07E−03

Phf6
12
0.278
0.127
0.764
1.23E−05
8.77E−03

H2-Q6
12
0.317
0.435
−0.578
1.40E−05
9.90E−03

Satb1
12
0.579
0.37
0.496
1.41E−05
9.95E−03

Itk
12
0.685
0.524
0.442
1.43E−05
1.01E−02

Fgl2
12
0.695
0.468
0.408
1.91E−05
1.31E−02

Hccs
12
0.26
0.094
0.922
1.97E−05
1.34E−02

Klf4
12
0.461
0.552
−0.505
2.38E−05
1.60E−02

Gnai2
12
0.593
0.625
−0.303
2.56E−05
1.70E−02

Ero1l
12
0.455
0.251
0.822
2.57E−05
1.71E−02

Mctp1
12
0.096
0.162
−0.729
2.67E−05
1.76E−02

Hes1
12
0.754
0.795
−0.548
3.77E−05
2.41E−02

Spry2
12
0.398
0.238
0.353
3.92E−05
2.49E−02

Tnfrsf1b
12
0.268
0.124
0.797
4.02E−05
2.55E−02

Nfatc1
12
0.274
0.147
0.680
5.51E−05
3.36E−02

Fam105a
12
0.445
0.256
0.498
5.70E−05
3.47E−02

Lpar6
12
0.285
0.354
−0.494
5.81E−05
3.53E−02

Serp1
12
0.807
0.8
−0.216
6.34E−05
3.77E−02

Psma6
12
0.291
0.266
−0.175
6.91E−05
4.07E−02

Vamp2
12
0.283
0.134
0.706
7.05E−05
4.14E−02

March7
12
0.278
0.127
0.738
7.22E−05
4.22E−02

Nfkbie
12
0.1
0.175
−0.749
7.56E−05
4.41E−02

Lrp10
12
0.39
0.18
0.808
7.58E−05
4.41E−02

Ssbp3
12
0.244
0.296
−0.425
7.84E−05
4.53E−02

Plscr1
12
0.463
0.301
0.580
8.32E−05
4.77E−02

Nfkbid
12
0.506
0.337
0.422
8.52E−05
4.87E−02

Tpt1
12
1
1
0.182
8.70E−05
4.94E−02

Wdr89
13
0.812
0.676
0.488
2.53E−12
5.48E−09

Uba52
13
0.753
0.655
0.423
1.79E−07
1.93E−04

Mcpt1
14
0.367
0.057
1.837
3.69E−21
2.05E−17

Mcpt2
14
0.234
0.017
2.435
6.32E−18
2.63E−14

Lyz1
14
0.05
0.24
−0.177
6.49E−14
1.71E−10

Defa24
14
0.106
0.333
−1.055
8.53E−13
1.99E−09

Grasp
14
0.633
0.77
−0.498
1.36E−12
3.09E−09

Id2
14
0.702
0.584
0.543
8.97E−09
1.21E−05

Nrros
14
0.578
0.325
0.796
1.23E−08
1.62E−05

Fabp2
14
0.046
0.19
−1.518
5.79E−08
6.87E−05

Rgs1
14
0.615
0.451
0.651
1.50E−07
1.65E−04

Ifrd1
14
0.674
0.751
−0.449
5.16E−07
5.05E−04

Sub1
14
1
0.988
−0.155
1.34E−06
1.20E−03

Cfp
14
0.904
0.91
−0.366
2.85E−06
2.41E−03

Maff
14
0.647
0.77
−0.329
3.56E−06
2.94E−03

Igkc
14
0.917
0.827
−1.522
4.43E−06
3.58E−03

Jund
14
0.94
0.95
−0.363
5.67E−06
4.44E−03

Anxa3
14
0.083
0.242
−1.191
1.00E−05
7.37E−03

Plac8
14
0.821
0.651
0.297
1.47E−05
1.03E−02

Plscr1
14
0.307
0.466
−0.634
1.47E−05
1.03E−02

Elf4
14
0.239
0.114
0.665
1.70E−05
1.17E−02

Igha
14
0.784
0.599
−0.973
1.97E−05
1.34E−02

AY036118
14
0.436
0.451
−0.392
2.01E−05
1.36E−02

Smap2
14
0.555
0.727
−0.418
2.43E−05
1.63E−02

Tbc1d4
14
0.761
0.81
−0.261
2.60E−05
1.73E−02

Ncl
14
0.872
0.867
−0.226
2.70E−05
1.78E−02

Elmsan1
14
0.193
0.323
−0.552
3.16E−05
2.06E−02

Arf4
14
0.775
0.824
−0.232
4.43E−05
2.78E−02

Ccr1
14
0.197
0.382
−0.803
4.54E−05
2.84E−02

Polr3c
14
0.298
0.173
0.494
4.90E−05
3.04E−02

Trps1
14
0.505
0.644
−0.415
6.20E−05
3.71E−02

Bex6
14
0.188
0.067
1.241
7.11E−05
4.16E−02

Birc2
14
0.252
0.354
−0.642
8.12E−05
4.68E−02

Tuba1c
14
0.367
0.368
−0.242
8.44E−05
4.83E−02

Jund
15
0.696
0.871
−0.886
1.14E−10
2.08E−07

Kdm6b
15
0.28
0.575
−0.851
2.25E−10
3.92E−07

Hk2
15
0.096
0.305
−1.074
1.32E−05
9.39E−03

Lmna
15
0.056
0.239
−1.137
1.33E−05
9.40E−03

Gimap6
15
0.48
0.333
0.667
2.10E−05
1.42E−02

Pnrc1
15
0.424
0.635
−0.562
3.36E−05
2.17E−02

Pim1
15
0.496
0.71
−0.599
6.51E−05
3.86E−02

Id2
15
0.728
0.514
0.579
8.76E−05
4.96E−02

Hes1
16
0.084
0.193
−1.843
5.36E−07
5.21E−04

Gpcpd1
16
0.118
0.22
−0.962
2.33E−06
2.02E−03

Dnaja1
16
0.382
0.487
−0.735
7.82E−06
5.88E−03

Ppp1r15a
16
0.189
0.293
−1.206
1.91E−05
1.31E−02

Sla
16
0.412
0.173
1.197
2.54E−05
1.70E−02

Cdk2ap2
16
0.08
0.167
−1.073
4.59E−05
2.87E−02

Gpr183
16
0.424
0.347
−0.256
8.06E−05
4.65E−02

Ptma
16
0.471
0.533
−0.390
8.17E−05
4.70E−02

Chchd10
17
0.235
0.11
0.792
5.97E−05
3.59E−02

Wdr89
18
1
0.96
0.510
1.74E−07
1.88E−04

Wsb1
18
0.038
0.169
−1.529
1.07E−05
7.83E−03

Junb
19
0.774
0.737
−0.245
2.79E−06
2.37E−03

Mcpt1
20
0.45
0.048
2.227
2.11E−10
3.69E−07

Mcpt2
20
0.321
0.01
3.407
1.02E−08
1.35E−05

Fabp2
20
0.061
0.276
−2.260
2.15E−06
1.87E−03

Lyz1
20
0.038
0.2
−2.380
1.19E−05
8.58E−03

Mcpt1
21
0.427
0.06
3.356
3.40E−09
4.92E−06

H2afz
21
0.983
0.991
−0.307
3.72E−06
3.06E−03

Defa24
21
0.248
0.444
−0.656
9.88E−06
7.29E−03

Ly6e
21
0.65
0.752
−0.726
1.02E−05
7.47E−03

Efhd2
21
0.889
0.915
−0.342
2.03E−05
1.37E−02

Nrros
21
0.658
0.436
0.861
2.90E−05
1.90E−02

Sla
21
0.863
0.744
0.496
3.49E−05
2.24E−02

Twf2
21
0.838
0.667
0.477
6.58E−05
3.89E−02

Hspa1a
21
0.556
0.47
0.298
7.00E−05
4.11E−02

Jund
22
0.898
0.947
−0.710
2.21E−07
2.34E−04

Gapdh
22
0.873
0.8
0.582
1.58E−06
1.40E−03

Trpv2
22
0.197
0
3.860
3.81E−06
3.11E−03

Pla2g2d
22
0.032
0.187
−2.738
3.41E−05
2.20E−02

Fam213b
22
0.051
0.173
−1.795
4.19E−05
2.65E−02

Hspa8
22
0.987
0.973
0.298
5.00E−05
3.09E−02

Lgals3bp
22
0.325
0.293
−0.597
5.93E−05
3.57E−02

Igha
24
0.688
0.263
1.262
6.96E−12
1.44E−08

Lyz1
24
0
0.175
−3.978
8.81E−07
8.17E−04

Mcpt1
24
0.257
0.035
3.554
1.05E−06
9.59E−04

Mcpt2
24
0.211
0.009
4.485
4.73E−06
3.78E−03

Arpp19
24
0.872
0.632
0.513
3.29E−05
2.13E−02

Ppp2r2d
24
0.083
0.254
−0.941
5.57E−05
3.40E−02

Egfl7
25
0.895
0.817
0.621
1.95E−07
2.09E−04

8430408G22Rik
25
0.702
0.341
1.076
4.38E−06
3.54E−03

Hspa1b
25
0.193
0.098
1.118
6.67E−06
5.12E−03

Fzd4
25
0.368
0.14
0.813
5.61E−05
3.42E−02

Actg1
26
1
0.976
0.880
2.14E−12
4.72E−09

Tph1
26
0.938
0.683
1.298
7.68E−12
1.58E−08

Alox5ap
26
0.926
0.659
1.357
5.00E−11
9.48E−08

Fcer1a
26
0.983
0.976
0.700
9.83E−10
1.55E−06

Mcpt2
26
0.955
0.634
1.631
1.74E−08
2.24E−05

Mcpt1
26
0.96
0.634
1.586
3.76E−08
4.61E−05

Decr1
26
0.682
0.171
1.704
4.35E−08
5.26E−05

Ms4a2
26
0.932
0.707
1.066
2.04E−07
2.18E−04

Itga2b
26
0.818
0.293
1.452
3.40E−07
3.45E−04

Ncor1
26
0.534
0.707
−0.936
3.88E−07
3.88E−04

Ero1l
26
0.739
0.293
1.562
5.25E−07
5.12E−04

Mcpt4
26
0.835
0.488
1.895
1.56E−06
1.39E−03

Sytl3
26
0.449
0.049
2.647
1.64E−06
1.45E−03

Ptpre
26
0.239
0.537
−1.096
1.78E−06
1.57E−03

Prnp
26
0.92
0.805
0.856
2.01E−06
1.76E−03

Fam105a
26
0.784
0.293
1.562
2.65E−06
2.28E−03

Gpr171
26
0.852
0.512
1.799
3.99E−06
3.25E−03

Vasp
26
0.892
0.537
1.081
4.68E−06
3.75E−03

Scin
26
0.966
0.61
0.960
4.70E−06
3.76E−03

Rac2
26
0.994
0.951
0.643
5.62E−06
4.40E−03

Igfbp4
26
0.045
0.244
−0.802
6.08E−06
4.71E−03

Pga5
26
0.307
0
4.663
7.06E−06
5.38E−03

Psip1
26
0.284
0.39
−0.818
7.61E−06
5.75E−03

Stk19
26
0.631
0.317
1.122
8.39E−06
6.28E−03

Atp1b1
26
0.92
0.659
0.831
1.53E−05
1.07E−02

Gm2a
26
0.938
0.854
0.723
1.63E−05
1.13E−02

Opa3
26
0.193
0.22
−0.937
1.68E−05
1.16E−02

Ftl1
26
1
1
0.846
3.43E−05
2.21E−02

Il4
26
0.784
0.659
1.307
5.53E−05
3.37E−02

Tacc1
26
0.415
0.122
0.633
5.83E−05
3.53E−02

Ptms
26
0.733
0.78
−0.473
6.46E−05
3.83E−02

Cox4i1
26
0.966
0.927
0.528
6.81E−05
4.02E−02

Sec11c
26
0.898
0.512
0.801
6.98E−05
4.10E−02

Zcchc10
26
0.46
0.122
0.773
8.08E−05
4.66E−02

Mknk2
26
0.205
0.317
−0.914
8.67E−05
4.93E−02

Mcpt1
27
0.177
0.017
2.416
2.33E−05
1.57E−02

Kdm6b
27
0.258
0.554
−1.318
4.79E−05
2.99E−02

Cd84
27
0.419
0.124
1.416
7.77E−05
4.50E−02

Zfp36l2
29
0.831
0.482
1.290
8.32E−07
7.75E−04

Tsc22d3
29
0.877
0.651
0.697
4.32E−05
2.72E−02

P2ry10
29
0.538
0.157
1.414
4.35E−05
2.74E−02

Dstn
30
0.857
0.99
−0.625
2.68E−06
2.29E−03

Ada
30
0.057
0.2
−4.360
5.72E−06
4.47E−03

Ubb
30
0.943
0.95
−0.641
1.25E−05
8.92E−03

Igkc
30
0.743
0.52
0.553
1.25E−05
8.92E−03

Apol9a
30
0
0.18
−4.300
7.19E−05
4.20E−02

Al413582
31
0.024
0.272
−2.863
5.52E−06
4.34E−03

Casq2
32
0.35
0.021
2.515
1.16E−05
8.34E−03

Thbs1
33
0.469
0.268
1.681
6.38E−05
3.80E−02

Mcpt2
34
0.491
0.07
1.799
1.14E−06
1.04E−03

Areg
34
0.018
0.186
1.280
2.27E−06
1.97E−03

Slc25a5
34
0.93
0.907
0.470
2.39E−06
2.06E−03

Mcpt1
34
0.474
0.07
2.144
7.59E−06
5.74E−03

Runx3
34
0.702
0.977
−0.675
8.83E−06
6.57E−03

Defa24
34
0.175
0.558
−1.480
1.20E−05
8.62E−03

Zmiz1
34
0.456
0.744
−0.901
1.67E−05
1.15E−02

Itm2b
34
0.947
0.977
0.362
3.72E−05
2.38E−02

Capns1
34
0.842
0.628
0.596
6.09E−05
3.65E−02

Whrn
34
0
0.186
−3.482
8.47E−05
4.84E−02

Xrcc6bp1
35
0
0.203
−3.388
1.10E−05
8.01E−03

Atf3
35
0.275
0.627
−0.517
4.05E−05
2.57E−02

Cxcl2
36
0.875
0.692
0.999
4.55E−06
3.66E−03

Dusp1
36
0.946
0.821
0.719
5.85E−06
4.56E−03

S100a8
36
0.982
0.795
1.265
7.62E−06
5.75E−03

Actg1
36
0.964
1
0.587
2.04E−05
1.38E−02

S100a9
36
0.946
0.923
1.043
3.43E−05
2.21E−02

G0s2
36
0.893
0.846
0.800
7.82E−05
4.52E−02

Il1b
36
0.982
1
0.474
8.19E−05
4.70E−02

Ptgs2
36
0.661
0.282
1.505
8.59E−05
4.90E−02

Hmgcs1
37
0
0.306
−4.058
5.86E−05
3.54E−02

Mcpt1
41
0.458
0
4.593
1.64E−05
1.14E−02

Alcam
41
0.583
0.04
2.248
1.93E−05
1.32E−02

Ptp4a3
41
0.625
1
−0.853
4.79E−05
2.99E−02

Acbd5
41
0.667
0.12
1.926
8.37E−05
4.80E−02

Itgal
42
0.375
0.125
−0.238
1.65E−07
1.80E−04

Reep5
43
0.786
0.5
0.884
6.46E−06
4.98E−03

Tceb2
44
0.588
0
6.153
2.88E−05
1.89E−02

B

percentage of
percentage of

expressing
expressing

cluster
cells in OVA-
cells in PBS-
LN (average

p value,

gene
ID
treated group
treated group
fold change)
p value
adjusted

Actb
1
1
0.968
1.320
1.82E−23
5.92E−20

Ighg1
1
0.372
0.008
3.863
2.30E−14
3.41E−11

Ptprcap
1
0.653
0.376
0.960
2.96E−09
2.23E−06

Igha
1
0.992
1
0.613
1.87E−08
1.23E−05

Pfn1
1
1
0.944
0.431
1.51E−07
8.39E−05

Emb
1
0.545
0.816
−0.648
4.11E−07
2.09E−04

Igkc
1
1
1
0.926
4.21E−07
2.13E−04

Ddit4
1
0.157
0
3.923
4.72E−07
2.36E−04

Mcpt1
1
0.157
0.008
2.804
1.94E−05
6.35E−03

Maff
1
0.107
0.32
−0.879
2.13E−05
6.90E−03

Cfl1
1
0.934
0.912
0.344
3.23E−05
9.88E−03

Rras2
1
0.099
0.296
−1.281
3.71E−05
1.12E−02

Dusp10
1
0.612
0.768
−0.557
4.19E−05
1.24E−02

Cnn2
1
0.678
0.424
0.641
4.42E−05
1.30E−02

Jun
1
0.438
0.232
1.206
4.47E−05
1.31E−02

Myl6
1
0.909
0.808
0.369
7.44E−05
2.03E−02

Ppp1r16b
1
0.281
0.072
1.323
7.72E−05
2.10E−02

Dusp5
1
0.289
0.552
−0.744
7.95E−05
2.15E−02

Igkv1-135
1
0.033
0.2
−1.720
9.18E−05
2.42E−02

Tmem71
1
0.066
0.264
−1.482
9.45E−05
2.48E−02

Rgs1
1
0.306
0.096
1.424
1.01E−04
2.62E−02

Hsp90ab1
1
0.76
0.624
0.546
1.07E−04
2.76E−02

Fam169b
1
0.033
0.184
−1.553
1.14E−04
2.91E−02

Cd52
1
0.893
0.816
0.412
1.17E−04
2.98E−02

Cct8
1
0.347
0.12
1.026
1.96E−04
4.59E−02

Mcpt1
11
0.167
0
4.314
3.70E−09
2.72E−06

Ikzf2
11
0.369
0.724
−0.930
5.16E−07
2.57E−04

Rgs1
11
0.821
0.704
0.745
1.31E−06
5.92E−04

Dusp2
11
0.464
0.24
1.175
2.06E−06
8.78E−04

Igha
11
0.988
0.913
0.278
2.41E−06
1.01E−03

Def6
11
0.357
0.112
1.164
1.66E−05
5.56E−03

Bhlhe40
11
0.429
0.73
−0.539
4.53E−05
1.33E−02

Top1
11
0.143
0.321
−0.475
4.63E−05
1.35E−02

Zfp36l2
11
0.774
0.663
0.442
6.65E−05
1.85E−02

Pdcd4
11
0.393
0.423
0.429
7.20E−05
1.97E−02

Rbm5
11
0.036
0.214
−2.020
7.61E−05
2.08E−02

Pim1
11
0.536
0.796
−0.640
8.10E−05
2.18E−02

Neat1
11
0.321
0.388
0.273
8.63E−05
2.30E−02

Napsa
11
0.25
0.092
0.833
1.74E−04
4.15E−02

Bcl2
11
0.821
0.755
0.439
2.11E−04
4.89E−02

Srgn
12
0.935
0.714
0.951
2.14E−85
1.55E−80

Hes1
12
0.487
0.871
−1.225
1.02E−69
4.26E−65

Sla
12
0.6
0.182
1.644
6.69E−66
2.59E−61

Ppp1r15a
12
0.4
0.741
−1.371
3.00E−64
1.03E−59

Furin
12
0.727
0.359
1.650
2.64E−63
7.31E−59

Actg1
12
0.926
0.77
0.782
4.58E−63
1.21E−58

Il13
12
0.445
0.093
2.748
4.80E−55
8.74E−51

Hspa8
12
0.929
0.783
0.644
3.71E−49
5.26E−45

Lilr4b
12
0.345
0.038
2.439
6.08 E−48
7.86E−44

4930523C07Rik
12
0.433
0.747
−0.954
5.86E−46
6.69E−42

Dnaja1
12
0.694
0.847
−0.898
5.15E−45
5.55E−41

Vps37b
12
0.568
0.811
−0.893
3.69E−43
3.64E−39

Nr4a3
12
0.524
0.169
1.521
2.56E−42
2.48E−38

Plaur
12
0.374
0.078
2.052
2.02E−40
1.78E−36

Fos
12
0.572
0.82
−1.132
1.82E−39
1.56E−35

Lif
12
0.263
0.022
2.855
5.25E−39
4.37E−35

Zfp36l1
12
0.938
0.82
0.631
6.03E−39
4.94E−35

Cxcr6
12
0.625
0.301
1.109
1.02E−37
7.81E−34

Sptssa
12
0.501
0.769
−0.841
8.77E−36
6.38E−32

Dusp1
12
0.62
0.867
−0.896
2.80E−33
1.79E−29

Ubb
12
0.919
0.965
−0.413
1.48E−32
8.78E−29

Plk3
12
0.285
0.051
1.772
8.17E−31
4.40E−27

Areg
12
0.498
0.224
1.394
2.69E−30
1.40E−26

Nab2
12
0.182
0.007
2.979
6.12E−30
3.12E−26

Pdcd1
12
0.244
0.033
2.125
1.16E−29
5.83E−26

Il4
12
0.519
0.301
1.409
2.35E−28
1.14E−24

Gcnt1
12
0.217
0.024
2.384
4.66E−28
2.19E−24

Jund
12
0.864
0.964
−0.512
5.58E−27
2.42E−23

Fosl2
12
0.614
0.332
0.801
3.42E−26
1.41E−22

H2-D1
12
0.972
0.995
−0.326
1.13E−25
4.46E−22

Tpt1
12
0.985
0.976
0.333
1.22E−25
4.76E−22

Prr7
12
0.09
0.281
−1.547
5.86E−25
2.22E−21

Sh2d2a
12
0.435
0.186
0.936
1.07E−24
3.90E−21

Esm1
12
0.018
0.173
−2.314
3.73E−24
1.29E−20

Crem
12
0.717
0.443
0.579
5.47E−24
1.88E−20

Fosb
12
0.412
0.616
−0.805
9.76E−24
3.28E−20

Rap1b
12
0.663
0.444
0.613
2.09E−23
6.74E−20

Csf2
12
0.258
0.067
1.960
2.13E−23
6.81E−20

Ptpn22
12
0.313
0.095
1.251
3.56E−23
1.12E−19

Lilrb4a
12
0.206
0.029
2.154
3.70E−23
1.16E−19

Lmo4
12
0.914
0.974
−0.391
1.10E−22
3.37E−19

Cdk11b
12
0.133
0.306
−1.282
2.16E−22
6.48E−19

Lgals7
12
0.291
0.08
1.511
2.32E−22
6.93E−19

Nfkbiz
12
0.729
0.525
0.624
3.17E−20
8.28E−17

Actb
12
0.964
0.903
0.686
1.26E−19
3.07E−16

Zap70
12
0.424
0.2
0.882
1.26E−19
3.07E−16

Fam46a
12
0.425
0.211
1.080
5.68E−19
1.32E−15

Dusp10
12
0.273
0.448
−0.820
5.80E−19
1.34E−15

Spry2
12
0.427
0.204
1.201
7.86E−19
1.79E−15

Cytip
12
0.625
0.392
0.531
1.50E−18
3.34E−15

Siah2
12
0.082
0.253
−1.422
1.68E−18
3.71E−15

Wnk1
12
0.398
0.197
0.971
2.95E−18
6.31E−15

Dtx1
12
0.05
0.197
−1.600
4.37E−18
9.28E−15

Tnfaip8
12
0.518
0.299
0.740
6.98E−18
1.45E−14

Fgl2
12
0.61
0.388
0.609
1.62E−17
3.21E−14

Prdx6
12
0.507
0.33
0.908
2.87E−17
5.57E−14

Tpm4
12
0.394
0.193
0.964
2.87E−17
5.57E−14

Serp1
12
0.554
0.692
−0.529
3.88E−17
7.46E−14

Ero1l
12
0.399
0.213
0.949
5.36E−17
1.01E−13

Uqcrh
12
0.765
0.596
0.450
6.48E−17
1.21E−13

Arl5c
12
0.04
0.173
−1.873
7.55E−17
1.39E−13

Coq10b
12
0.332
0.521
−0.690
9.27E−17
1.69E−13

Pfn1
12
0.974
0.962
0.233
9.91E−17
1.80E−13

Sepp1
12
0.254
0.439
−0.824
1.47E−16
2.64E−13

Ucp2
12
0.612
0.43
0.519
4.62E−16
8.09E−13

Pnrc1
12
0.583
0.774
−0.457
5.82E−16
1.00E−12

Gpr132
12
0.399
0.539
−0.573
1.25E−15
2.09E−12

Tiparp
12
0.18
0.33
−0.904
1.88E−15
3.10E−12

Hccs
12
0.243
0.08
1.079
3.32E−15
5.37E−12

Eef1a1
12
0.997
0.995
0.236
4.21E−15
6.72E−12

Lmna
12
0.045
0.173
−1.627
4.61E−15
7.30E−12

Cd52
12
0.581
0.397
0.644
4.69E−15
7.38E−12

Cycs
12
0.531
0.337
0.561
4.96E−15
7.79E−12

Igha
12
0.951
0.907
0.407
6.51E−15
1.02E−11

Rheb
12
0.536
0.342
0.631
1.00E−14
1.54E−11

Igkc
12
0.985
0.974
0.474
1.09E−14
1.68E−11

Kif23
12
0.102
0.259
−1.129
1.13E−14
1.71E−11

Cited2
12
0.176
0.375
−0.724
1.18E−14
1.79E−11

Klf4
12
0.336
0.537
−0.566
3.70E−14
5.32E−11

Nfkb1
12
0.81
0.674
0.501
4.40E−14
6.26E−11

BC031181
12
0.365
0.454
−0.512
5.80E−14
8.17E−11

Ramp3
12
0.561
0.342
0.516
7.44E−14
1.03E−10

Cwc25
12
0.061
0.188
−1.439
9.00E−14
1.24E−10

Scp2
12
0.382
0.559
−0.568
9.01E−14
1.24E−10

Eif3e
12
0.67
0.512
0.416
2.54E−13
3.33E−10

Tnfaip3
12
0.534
0.643
−0.487
2.72E−13
3.55E−10

Irf1
12
0.069
0.206
−1.336
2.81E−13
3.66E−10

Nrgn
12
0.284
0.12
1.042
3.57E−13
4.57E−10

Abhd17c
12
0.52
0.324
0.599
5.00E−13
6.29E−10

Glul
12
0.184
0.339
−1.009
6.84E−13
8.52E−10

Vmp1
12
0.239
0.093
1.019
8.14E−13
1.01E−09

Gmfg
12
0.31
0.142
0.821
1.34E−12
1.62E−09

Tmem64
12
0.41
0.224
0.605
1.76E−12
2.11E−09

Rnf19b
12
0.279
0.118
0.971
3.11E−12
3.58E−09

Naca
12
0.839
0.723
0.299
4.17E−12
4.76E−09

Gimap5
12
0.338
0.179
0.779
8.34E−12
9.16E−09

Arf6
12
0.429
0.268
0.610
9.31E−12
1.01E−08

Tmsb4x
12
1
1
0.195
9.66E−12
1.05E−08

Eef1b2
12
0.709
0.554
0.395
1.30E−11
1.39E−08

Eif1
12
0.996
0.989
0.152
1.86E−11
1.96E−08

Arpc2
12
0.769
0.654
0.318
2.02E−11
2.12E−08

H2-Q4
12
0.246
0.41
−0.675
2.07E−11
2.17E−08

Gpx4
12
0.818
0.887
−0.345
2.52E−11
2.63E−08

Emd
12
0.235
0.353
−0.729
2.83E−11
2.94E−08

Polr2e
12
0.091
0.226
−1.019
4.42E−11
4.49 E−08

Tspan13
12
0.699
0.787
−0.366
4.65E−11
4.69E−08

Zc3h12a
12
0.157
0.301
−0.866
8.60E−11
8.39E−08

Itk
12
0.515
0.332
0.495
8.94E−11
8.69E−08

Maff
12
0.399
0.519
−0.518
9.49E−11
9.18E−08

Rsrp1
12
0.24
0.386
−0.708
1.16E−10
1.11E−07

Tgfb1
12
0.457
0.293
0.625
1.48E−10
1.39E−07

Ptp4a1
12
0.349
0.466
−0.514
1.88E−10
1.74E−07

Gapdh
12
0.561
0.434
0.420
2.03E−10
1.87E−07

Ly6a
12
0.055
0.173
−1.208
2.28E−10
2.09E−07

Iglc1
12
0.184
0.311
−0.692
2.55E−10
2.32E−07

Psap
12
0.299
0.437
−0.562
3.21E−10
2.88E−07

Pole4
12
0.604
0.457
0.415
3.83E−10
3.35E−07

Cox8a
12
0.798
0.71
0.285
3.88E−10
3.38E−07

Ndfip1
12
0.247
0.109
0.765
4.09E−10
3.56E−07

Eef2
12
0.927
0.898
0.240
5.72E−10
4.91E−07

Tgoln1
12
0.215
0.326
−0.572
5.85E−10
5.00E−07

Jarid2
12
0.156
0.046
1.269
6.36E−10
5.40E−07

Galnt12
12
0.086
0.209
−0.960
7.06E−10
5.97E−07

Ddx5
12
0.886
0.931
−0.276
7.94E−10
6.71E−07

Kdm6b
12
0.65
0.47
0.555
9.04E−10
7.58E−07

Pgm2l1
12
0.065
0.177
−0.966
1.03E−09
8.51E−07

Tspan32
12
0.073
0.184
−0.997
1.15E−09
9.39E−07

Zfp36l2
12
0.49
0.448
0.453
1.17E−09
9.52E−07

Fth1
12
0.963
0.989
−0.236
1.23E−09
1.00E−06

Ubc
12
0.303
0.446
−0.542
1.29E−09
1.04E−06

Mat2a
12
0.288
0.415
−0.572
1.34E−09
1.08E−06

Nxpe3
12
0.202
0.082
0.974
1.64E−09
1.30E−06

Cbarp
12
0.193
0.077
0.886
1.74E−09
1.38E−06

Nr4a2
12
0.383
0.259
0.702
2.50E−09
1.92E−06

H3f3b
12
0.982
0.982
0.286
2.59E−09
1.98E−06

Fxyd5
12
0.564
0.432
0.407
2.82E−09
2.14E−06

Neurl3
12
0.328
0.439
−0.470
3.18E−09
2.38E−06

Arl4a
12
0.256
0.128
0.781
3.23E−09
2.40E−06

Psmb10
12
0.219
0.335
−0.598
3.50E−09
2.60E−06

Cntnap2
12
0.074
0.175
−1.008
4.85E−09
3.50E−06

Usmg5
12
0.509
0.585
−0.414
5.00E−09
3.60E−06

Zrsr1
12
0.242
0.337
−0.652
5.12E−09
3.68E−06

H2afj
12
0.433
0.29
0.452
7.92E−09
5.53E−06

Ccrl2
12
0.192
0.308
−0.742
8.29E−09
5.78E−06

Psmb8
12
0.49
0.627
−0.441
8.39E−09
5.84E−06

Tmsb10
12
0.942
0.976
−0.240
1.08E−08
7.39E−06

Ccl1
12
0.203
0.084
1.335
1.17E−08
7.93E−06

Saraf
12
0.304
0.435
−0.533
1.19E−08
8.02E−06

Uhrf2
12
0.296
0.424
−0.506
1.19E−08
8.02E−06

Eif3h
12
0.686
0.568
0.298
1.64E−08
1.09E−05

Srsf7
12
0.251
0.311
−0.443
2.24E−08
1.45E−05

Hmgb1
12
0.552
0.687
−0.400
2.28E−08
1.47E−05

H2-K1
12
0.921
0.958
−0.243
2.81E−08
1.79E−05

Gypc
12
0.256
0.133
0.686
2.89E−08
1.84E−05

Dbp
12
0.059
0.151
−1.018
3.11E−08
1.96E−05

Lcp2
12
0.339
0.208
0.544
3.75E−08
2.32E−05

Pnn
12
0.123
0.235
−0.769
3.80E−08
2.35E−05

Nab1
12
0.193
0.082
0.888
3.94E−08
2.42E−05

2810474O19Rik
12
0.099
0.195
−0.835
4.39E−08
2.67E−05

Hist1h1c
12
0.205
0.102
1.035
4.46E−08
2.71E−05

Pdcd1lg2
12
0.223
0.109
0.833
4.95E−08
2.98E−05

Tmem59
12
0.332
0.463
−0.485
5.65E−08
3.37E−05

Tapbp
12
0.287
0.403
−0.510
5.78E−08
3.44E−05

Tob2
12
0.328
0.434
−0.479
6.05E−08
3.57E−05

Hmha1
12
0.206
0.333
−0.645
6.95E−08
4.06E−05

Slc3a2
12
0.47
0.321
0.469
7.95E−08
4.59E−05

Fam189b
12
0.116
0.226
−0.759
9.57E−08
5.44E−05

Churc1
12
0.258
0.357
−0.570
1.08E−07
6.12E−05

Clk1
12
0.269
0.362
−0.438
1.26E−07
7.07E−05

Cox4i1
12
0.836
0.765
0.208
1.70E−07
9.31E−05

Tprgl
12
0.291
0.401
−0.513
1.76E−07
9.63E−05

Rnf167
12
0.098
0.2
−0.794
1.93E−07
1.05E−04

Eprs
12
0.133
0.231
−0.676
2.01E−07
1.09E−04

Polr2j
12
0.099
0.206
−0.824
2.02E−07
1.09E−04

Slc25a5
12
0.458
0.352
0.368
2.12E−07
1.14E−04

Ak2
12
0.288
0.169
0.603
2.14E−07
1.15E−04

Cd53
12
0.687
0.566
0.260
2.45E−07
1.30E−04

Jun
12
0.456
0.534
−0.614
2.67E−07
1.41E−04

Nr3c1
12
0.487
0.346
0.471
2.92E−07
1.53E−04

Srrm2
12
0.433
0.455
−0.241
3.14E−07
1.63E−04

Selk
12
0.749
0.661
0.258
3.40E−07
1.75E−04

Cotl1
12
0.481
0.61
−0.396
3.52E−07
1.80E−04

Hsp90ab1
12
0.585
0.485
0.369
3.91E−07
1.99E−04

Bcl11b
12
0.115
0.215
−0.742
4.36E−07
2.20E−04

Taldo1
12
0.399
0.508
−0.406
4.61E−07
2.31E−04

Orai1
12
0.247
0.129
0.719
4.95E−07
2.47E−04

Pfdn5
12
0.778
0.69
0.229
6.11E−07
2.99E−04

Rxrg
12
0.089
0.191
−0.813
6.16E−07
3.01E−04

Maf1
12
0.122
0.209
−0.730
6.66E−07
3.23E−04

Spcs2
12
0.583
0.709
−0.346
7.47E−07
3.56E−04

Ralbp1
12
0.26
0.362
−0.471
7.89E−07
3.75E−04

Hlf
12
0.25
0.135
0.620
8.37E−07
3.95E−04

Smco4
12
0.185
0.089
1.106
9.51E−07
4.44E−04

Fam102a
12
0.31
0.191
0.548
1.08E−06
5.00E−04

Btg2
12
0.945
0.9
0.203
1.08E−06
5.01E−04

Rab26os
12
0.094
0.175
−0.713
1.09E−06
5.02E−04

Runx3
12
0.194
0.31
−0.586
1.27E−06
5.77E−04

Cd47
12
0.312
0.393
−0.415
1.28E−06
5.82E−04

Fam32a
12
0.169
0.255
−0.572
1.33E−06
5.97E−04

Dusp5
12
0.563
0.43
0.426
1.53E−06
6.77E−04

Rgs2
12
0.832
0.796
0.360
1.61E−06
7.11E−04

Lgals9
12
0.156
0.244
−0.599
1.68E−06
7.36E−04

Sec11c
12
0.403
0.51
−0.377
1.84E−06
7.99E−04

Zyx
12
0.188
0.093
0.712
1.85E−06
8.02E−04

Eif4a1
12
0.671
0.585
0.213
2.01E−06
8.59E−04

Nkg7
12
0.445
0.57
−0.379
2.34E−06
9.88E−04

1500011K16Rik
12
0.135
0.157
−0.378
2.46E−06
1.03E−03

Rsbn1l
12
0.157
0.2
−0.441
2.47E−06
1.03E−03

Hmgn2
12
0.091
0.182
−0.797
2.67E−06
1.10E−03

Npm1
12
0.704
0.623
0.255
2.73E−06
1.13E−03

Srsf3
12
0.35
0.468
−0.403
2.77E−06
1.14E−03

Arpc5
12
0.507
0.386
0.280
2.97E−06
1.21E−03

Cox7a2
12
0.621
0.51
0.217
2.98E−06
1.21E−03

Cmtm6
12
0.099
0.195
−0.711
3.16E−06
1.27E−03

Asb2
12
0.219
0.131
0.449
3.36E−06
1.35E−03

Rap1a
12
0.338
0.226
0.514
3.50E−06
1.39E−03

Map1lc3a
12
0.217
0.284
−0.448
3.60E−06
1.43E−03

Ier2
12
0.663
0.747
−0.498
3.87E−06
1.52E−03

Eif3m
12
0.406
0.29
0.403
3.88E−06
1.52E−03

Hspa4
12
0.247
0.142
0.563
4.09E−06
1.60E−03

Neat1
12
0.329
0.22
0.571
4.14E−06
1.62E−03

1110004F10Rik
12
0.148
0.233
−0.584
4.25E−06
1.66E−03

Ikzf2
12
0.181
0.237
−0.586
4.85E−06
1.87E−03

Polr2m
12
0.214
0.308
−0.492
5.09E−06
1.96E−03

Itpkb
12
0.277
0.189
0.222
5.10E−06
1.96E−03

Tubb4b
12
0.086
0.157
−0.768
5.16E−06
1.98E−03

Tbck
12
0.153
0.239
−0.562
5.24E−06
2.01E−03

Vrk1
12
0.144
0.233
−0.650
5.58E−06
2.12E−03

Ago2
12
0.207
0.107
0.728
5.85E−06
2.21E−03

Tsc22d3
12
0.255
0.357
−0.557
5.98E−06
2.25E−03

Ppp1r16b
12
0.279
0.162
0.621
6.17E−06
2.32E−03

Dhx40
12
0.184
0.086
0.750
6.25E−06
2.35E−03

Cmc2
12
0.203
0.255
−0.410
6.86E−06
2.55E−03

Lcp1
12
0.314
0.206
0.393
6.99E−06
2.59E−03

Gnb2l1
12
0.76
0.701
0.257
7.40E−06
2.72E−03

Taf7
12
0.09
0.153
−0.639
7.50E−06
2.76E−03

Faah
12
0.178
0.288
−0.572
7.99E−06
2.91E−03

Trappc6b
12
0.267
0.273
−0.211
8.10E−06
2.95E−03

Nsa2
12
0.299
0.191
0.379
8.74E−06
3.16E−03

Ip6k1
12
0.083
0.157
−0.767
8.97E−06
3.23E−03

Tnfrsf1b
12
0.16
0.073
0.769
8.99E−06
3.23E−03

Sh3bgrl3
12
0.754
0.803
−0.224
9.42E−06
3.37E−03

Abhd17b
12
0.091
0.173
−0.752
9.44E−06
3.38E−03

Calm3
12
0.329
0.432
−0.423
9.69E−06
3.46E−03

Hsp90aa1
12
0.387
0.299
0.543
9.73E−06
3.48E−03

Ddx3x
12
0.433
0.308
0.376
1.06E−05
3.75E−03

Ramp1
12
0.148
0.244
−0.600
1.13E−05
3.96E−03

Ndel1
12
0.09
0.158
−0.699
1.15E−05
4.02E−03

Pebp1
12
0.255
0.342
−0.433
1.19E−05
4.13E−03

Tonsl
12
0.402
0.472
−0.339
1.30E−05
4.49E−03

Kcnn4
12
0.111
0.2
−0.711
1.35E−05
4.66E−03

Cldnd1
12
0.238
0.144
0.683
1.37E−05
4.70E−03

Ssbp2
12
0.106
0.164
−0.559
1.61E−05
5.43E−03

Arl2bp
12
0.14
0.222
−0.567
1.63E−05
5.48E−03

Tgm2
12
0.116
0.188
−0.651
1.68E−05
5.61E−03

Lsp1
12
0.285
0.353
−0.396
1.88E−05
6.19E−03

Rbm5
12
0.11
0.171
−0.602
1.91E−05
6.27E−03

Glrx
12
0.314
0.222
0.253
1.93E−05
6.33E−03

Tnfrsf18
12
0.523
0.541
−0.238
1.97E−05
6.44E−03

Arih1
12
0.136
0.171
−0.537
2.05E−05
6.70E−03

Dad1
12
0.495
0.501
−0.321
2.28E−05
7.31E−03

Hmgb2
12
0.382
0.488
−0.362
2.42E−05
7.71E−03

Zcchc10
12
0.213
0.124
0.523
2.66E−05
8.33E−03

Mkrn1
12
0.231
0.242
−0.228
2.69E−05
8.40E−03

Slc6a13
12
0.122
0.209
−0.662
2.89E−05
8.96E−03

Gpsm3
12
0.413
0.521
−0.352
2.91E−05
9.01E−03

Tmem30a
12
0.326
0.222
0.395
3.02E−05
9.33E−03

Klf3
12
0.147
0.239
−0.583
3.06E−05
9.43E−03

Cd7
12
0.075
0.155
−0.714
3.07E−05
9.44E−03

Eif3f
12
0.769
0.699
0.189
3.24E−05
9.88E−03

Alad
12
0.184
0.271
−0.500
3.57E−05
1.08E−02

Al413582
12
0.091
0.168
−0.699
3.74E−05
1.12E−02

Mat2b
12
0.111
0.2
−0.636
3.84E−05
1.15E−02

Polr2i
12
0.104
0.171
−0.674
3.93E−05
1.18E−02

Icos
12
0.281
0.386
−0.356
4.44E−05
1.31E−02

Rbms1
12
0.226
0.268
−0.300
4.91E−05
1.42E−02

Cstb
12
0.197
0.253
−0.548
4.94E−05
1.43E−02

Atp5g2
12
0.552
0.448
0.219
4.99E−05
1.44E−02

Tmem176a
12
0.199
0.293
−0.544
5.21E−05
1.49E−02

Cd27
12
0.402
0.293
0.409
5.26E−05
1.51E−02

Aprt
12
0.284
0.182
0.449
5.37E−05
1.54E−02

Lbr
12
0.148
0.211
−0.498
5.49E−05
1.57E−02

Rasa2
12
0.184
0.098
0.665
5.87E−05
1.66E−02

Ypel3
12
0.375
0.483
−0.375
6.04E−05
1.70E−02

Ndufs7
12
0.21
0.281
−0.413
6.04E−05
1.70E−02

Tapbpl
12
0.099
0.162
−0.629
6.06E−05
1.70E−02

G3bp1
12
0.239
0.317
−0.433
6.09E−05
1.71E−02

Rassf5
12
0.247
0.155
0.458
6.58E−05
1.83E−02

Zc3h15
12
0.21
0.124
0.524
6.80E−05
1.89E−02

Arpc4
12
0.39
0.301
0.362
6.96E−05
1.92E−02

Ppp1r10
12
0.11
0.164
−0.520
6.99E−05
1.93E−02

Dusp11
12
0.217
0.126
0.563
7.03E−05
1.94E−02

Cd37
12
0.332
0.231
0.368
7.13E−05
1.96E−02

Tmem14c
12
0.127
0.184
−0.538
7.16E−05
1.96E−02

Hnrnpu
12
0.281
0.193
0.435
7.90E−05
2.14E−02

Ptprc
12
0.441
0.333
0.327
8.06E−05
2.18E−02

Abracl
12
0.357
0.251
0.406
8.08E−05
2.18E−02

Cisd2
12
0.388
0.288
0.253
8.08E−05
2.18E−02

Ikzf1
12
0.226
0.322
−0.460
8.56E−05
2.28E−02

Hcst
12
0.437
0.33
0.253
8.85E−05
2.35E−02

Elovl5
12
0.32
0.242
0.152
8.97E−05
2.38E−02

Rnf166
12
0.131
0.199
−0.569
8.98E−05
2.38E−02

Bst2
12
0.086
0.16
−0.675
9.00E−05
2.38E−02

Polr2k
12
0.301
0.213
0.266
9.18E−05
2.42E−02

Med28
12
0.32
0.337
−0.202
9.36E−05
2.46E−02

Baz1a
12
0.256
0.162
0.496
9.63E−05
2.52E−02

Ifnar1
12
0.209
0.308
−0.459
9.91E−05
2.58E−02

Gpcpd1
12
0.107
0.182
−0.607
1.02E−04
2.66E−02

Zfand5
12
0.157
0.242
−0.525
1.03E−04
2.66E−02

Gbp7
12
0.115
0.199
−0.681
1.03E−04
2.67E−02

Rsrc2
12
0.24
0.299
−0.365
1.05E−04
2.72E−02

Birc3
12
0.255
0.27
−0.292
1.07E−04
2.75E−02

Elf1
12
0.378
0.397
−0.249
1.16E−04
2.95E−02

Ipmk
12
0.226
0.138
0.375
1.30E−04
3.26E−02

Tmed9
12
0.207
0.282
−0.424
1.36E−04
3.38E−02

Rab37
12
0.119
0.188
−0.598
1.42E−04
3.51E−02

Sumo3
12
0.119
0.191
−0.580
1.58E−04
3.82E−02

Pura
12
0.103
0.179
−0.588
1.59E−04
3.84E−02

Ifrd1
12
0.428
0.536
−0.210
1.60E−04
3.84E−02

Btf3
12
0.716
0.643
0.151
1.61E−04
3.88E−02

Zc3hav1
12
0.336
0.393
−0.304
1.62E−04
3.90E−02

Map1lc3b
12
0.415
0.505
−0.322
1.73E−04
4.14E−02

Bnip3l
12
0.281
0.346
−0.334
1.76E−04
4.18E−02

Timm13
12
0.244
0.324
−0.449
1.76E−04
4.19E−02

Cox17
12
0.436
0.352
0.301
1.88E−04
4.42E−02

Gpr171
12
0.24
0.151
0.538
1.92E−04
4.50E−02

Rela
12
0.122
0.193
−0.563
1.97E−04
4.60E−02

Pim3
12
0.196
0.12
0.737
2.02E−04
4.70E−02

Ccr4
12
0.166
0.087
0.675
2.09E−04
4.84E−02

Mcpt1
13
0.31
0.014
4.351
6.62E−07
3.21E−04

Mcpt2
13
0.319
0.028
3.840
8.50E−06
3.08E−03

Vps37b
13
0.168
0.514
−1.238
3.79E−05
1.14E−02

Malat1
13
0.956
1
−0.616
4.18E−05
1.24E−02

Prkca
13
0.053
0.292
−1.342
8.86E−05
2.35E−02

Mcpt4
13
0.212
0.014
2.758
1.22E−04
3.09E−02

Btg1
13
0.664
0.847
−0.619
1.41E−04
3.49E−02

Actb
13
0.991
0.986
0.469
1.42E−04
3.51E−02

Igkc
13
0.973
0.931
1.825
2.03E−04
4.72E−02

Hspa1a
14
0.313
0.039
3.041
1.60E−28
7.81E−25

Ighg1
14
0.232
0.013
3.120
3.10E−26
1.29E−22

Tnfaip2
14
0.367
0.703
−1.159
3.56E−24
1.24E−20

Hspa1b
14
0.181
0.009
3.382
1.25E−20
3.34E−17

Mcpt1
14
0.201
0.009
4.922
2.24E−19
5.41E−16

Iglc1
14
0.444
0.672
−0.883
3.05E−19
7.27E−16

Mcpt2
14
0.17
0.006
4.456
7.66E−18
1.58E−14

Btg2
14
0.977
0.985
−0.289
3.88E−17
7.46E−14

Actg1
14
1
1
0.419
6.17E−17
1.16E−13

Igkv1-135
14
0.058
0.239
−1.531
6.21E−14
8.71E−11

Zfp36
14
0.938
0.88
0.502
3.47E−12
3.96E−09

Dab2
14
0.201
0.053
1.466
9.95E−12
1.08E−08

Pilra
14
0.359
0.565
−0.586
5.41E−11
5.42E−08

Hspa8
14
0.992
0.98
0.479
6.08E−11
6.05E−08

Xlr
14
0.278
0.483
−0.746
9.04E−11
8.77E−08

Ccr1
14
0.317
0.532
−0.504
1.54E−10
1.45E−07

Fosb
14
0.564
0.746
−0.494
1.88E−10
1.74E−07

Nr4a2
14
0.483
0.68
−0.509
3.73E−10
3.27E−07

Ppia
14
0.996
0.982
0.386
3.86E−10
3.38E−07

Neat1
14
0.834
0.674
0.555
5.52E−10
4.76E−07

Jun
14
0.687
0.453
0.769
5.88E−10
5.02E−07

Id2
14
0.514
0.324
0.997
6.84E−10
5.79E−07

Hsp90aa1
14
0.714
0.562
0.738
9.01E−10
7.57E−07

Arl4c
14
0.344
0.51
−0.709
1.01E−09
8.37E−07

Srsf5
14
0.822
0.851
−0.304
1.24E−09
1.01E−06

Lgals3
14
0.892
0.913
−0.323
1.36E−09
1.09E−06

Agpat4
14
0.436
0.593
−0.568
2.57E−09
1.96E−06

Vps37b
14
0.27
0.459
−0.748
2.60E−09
1.99E−06

Il1b
14
0.749
0.891
−0.287
3.12E−09
2.33E−06

Cxcr4
14
0.456
0.223
1.002
4.01E−09
2.93E−06

S100a6
14
0.707
0.448
0.622
8.77E−09
6.07E−06

Arid5a
14
0.251
0.411
−0.640
9.84E−09
6.75E−06

Hsp90ab1
14
0.961
0.893
0.435
1.37E−08
9.20E−06

Fam110a
14
0.212
0.343
−0.815
2.00E−08
1.31E−05

Zfp36l1
14
0.629
0.468
0.618
2.43E−08
1.56E−05

Ebi3
14
0.166
0.32
−0.957
2.66E−08
1.70E−05

Fam43a
14
0.066
0.201
−1.331
2.73E−08
1.74E−05

Il1r2
14
0.618
0.781
−0.400
2.84E−08
1.81E−05

Ifi30
14
0.911
0.812
0.500
3.14E−08
1.98E−05

Gp2
14
0.089
0.225
−1.351
3.20E−08
2.01E−05

Lin54
14
0.131
0.256
−0.872
3.81E−08
2.35E−05

Igkv12-44
14
0.174
0.042
1.266
3.88E−08
2.39E−05

Napsa
14
0.942
0.858
0.442
4.76E−08
2.89E−05

Cfp
14
0.873
0.72
0.517
5.80E−08
3.45E−05

Zfand5
14
0.66
0.766
−0.528
6.61E−08
3.89E−05

Ppp1r1a
14
0.166
0.319
−0.969
7.77E−08
4.51E−05

Ifrd1
14
0.707
0.792
−0.477
7.82E−08
4.54E−05

Lacc1
14
0.104
0.215
−0.999
8.10E−08
4.67E−05

Syngr2
14
0.903
0.75
0.460
1.23E−07
6.93E−05

Rgs2
14
0.622
0.751
−0.310
1.59E−07
8.79E−05

Gapdh
14
0.946
0.904
0.411
2.77E−07
1.45E−04

Fth1
14
1
1
−0.206
4.16E−07
2.11E−04

Icam1
14
0.44
0.486
−0.618
5.47E−07
2.70E−04

Ptp4a1
14
0.595
0.696
−0.383
8.24E−07
3.90E−04

Tyrobp
14
0.961
0.971
−0.247
9.57E−07
4.47E−04

Klf4
14
0.32
0.462
−0.399
1.19E−06
5.44E−04

Hck
14
0.336
0.44
−0.460
1.48E−06
6.57E−04

S100a4
14
0.324
0.151
0.620
1.50E−06
6.67E−04

Ltc4s
14
0.124
0.252
−0.891
1.75E−06
7.63E−04

Ms4a4c
14
0.189
0.083
1.398
1.80E−06
7.85E−04

Tiparp
14
0.151
0.295
−0.903
1.82E−06
7.90E−04

Cxcl16
14
0.506
0.643
−0.436
1.87E−06
8.11E−04

Cd33
14
0.247
0.383
−0.680
1.93E−06
8.30E−04

Hepacam2
14
0.054
0.164
−1.349
2.42E−06
1.02E−03

Prdm1
14
0.042
0.16
−1.404
2.46E−06
1.03E−03

Atp5b
14
0.919
0.805
0.377
2.48E−06
1.04E−03

DynIl1
14
0.9
0.777
0.382
2.55E−06
1.06E−03

Ckb
14
0.784
0.606
0.493
2.87E−06
1.17E−03

Clec4n
14
0.247
0.413
−0.710
3.02E−06
1.23E−03

Slc25a5
14
0.938
0.88
0.383
3.32E−06
1.33E−03

Atp5c1
14
0.88
0.775
0.382
3.73E−06
1.47E−03

Plet1
14
0.293
0.438
−0.497
3.83E−06
1.51E−03

Hspd1
14
0.556
0.359
0.665
3.83E−06
1.51E−03

Atp5h
14
0.923
0.827
0.331
3.98E−06
1.56E−03

Zfp263
14
0.398
0.514
−0.502
4.63E−06
1.79E−03

AW112010
14
0.382
0.516
−0.201
4.80E−06
1.86E−03

AF251705
14
0.363
0.49
−0.523
5.32E−06
2.03E−03

Nfkbiz
14
0.436
0.556
−0.644
6.23E−06
2.34E−03

Ndel1
14
0.363
0.481
−0.517
6.57E−06
2.45E−03

Klf6
14
0.718
0.61
0.429
7.19E−06
2.66E−03

Tubb5
14
0.768
0.6
0.542
7.30E−06
2.70E−03

Spg21
14
0.486
0.567
−0.361
7.69E−06
2.82E−03

Tmem50b
14
0.29
0.413
−0.480
9.27E−06
3.33E−03

Ak2
14
0.537
0.394
0.597
1.05E−05
3.72E−03

Lair1
14
0.12
0.206
−0.772
1.12E−05
3.95E−03

Atf3
14
0.548
0.698
−0.156
1.17E−05
4.10E−03

Irf1
14
0.135
0.262
−1.045
1.19E−05
4.13E−03

Tnni2
14
0.722
0.803
−0.164
1.33E−05
4.59E−03

Sdc4
14
0.205
0.087
0.976
1.42E−05
4.85E−03

Zbtb46
14
0.22
0.094
0.654
1.43E−05
4.87E−03

Ninj1
14
0.201
0.348
−0.685
1.47E−05
5.01E−03

Tuba1b
14
0.761
0.545
0.479
1.50E−05
5.10E−03

Clta
14
0.884
0.807
0.346
1.52E−05
5.16E−03

Nlrp3
14
0.301
0.433
−0.656
1.62E−05
5.46E−03

Neurl3
14
0.479
0.597
−0.385
1.73E−05
5.76E−03

Mt1
14
0.448
0.617
−0.720
1.73E−05
5.76E−03

Tkt
14
0.672
0.499
0.513
1.91E−05
6.27E−03

Erlin1
14
0.158
0.274
−0.606
1.96E−05
6.43E−03

Dph3
14
0.336
0.416
−0.452
2.08E−05
6.76E−03

Rnaset2a
14
0.757
0.775
−0.247
2.21E−05
7.10E−03

Rasgef1b
14
0.541
0.348
0.369
2.26E−05
7.23E−03

Rhob
14
0.255
0.129
1.055
2.32E−05
7.43E−03

Iglv1
14
0.093
0.186
−0.608
2.33E−05
7.44E−03

Fgl2
14
0.452
0.571
−0.427
2.51E−05
7.94E−03

Gsg1
14
0.093
0.204
−0.956
2.58E−05
8.14E−03

Rap1b
14
0.842
0.816
−0.198
2.62E−05
8.21E−03

Npm1
14
0.958
0.906
0.310
2.79E−05
8.67E−03

Tm2d2
14
0.502
0.558
−0.386
2.87E−05
8.93E−03

Lmo2
14
0.49
0.578
−0.320
2.90E−05
9.00E−03

Pcyt2
14
0.189
0.293
−0.536
2.94E−05
9.12E−03

Runx1
14
0.274
0.379
−0.623
3.24E−05
9.89E−03

Ppp1r15a
14
0.653
0.595
−0.405
3.28E−05
1.00E−02

Sla
14
0.633
0.49
0.504
3.29E−05
1.00E−02

Crem
14
0.355
0.455
−0.536
3.78E−05
1.14E−02

Pa2g4
14
0.583
0.372
0.564
3.90E−05
1.17E−02

Vim
14
0.923
0.84
0.314
4.07E−05
1.21E−02

Dusp1
14
0.838
0.759
0.380
4.34E−05
1.28E−02

Ltb
14
0.618
0.573
0.582
4.68E−05
1.36E−02

Ctage5
14
0.498
0.6
−0.293
4.91E−05
1.42E−02

Nuak2
14
0.208
0.331
−0.566
5.87E−05
1.66E−02

Btg1
14
0.973
0.989
−0.221
5.87E−05
1.66E−02

Cxx1b
14
0.228
0.368
−0.572
6.28E−05
1.75E−02

Aif1
14
0.363
0.495
−0.259
6.54E−05
1.82E−02

Herpud1
14
0.703
0.737
−0.254
6.61E−05
1.84E−02

Ifnar1
14
0.309
0.401
−0.505
7.81E−05
2.12E−02

Atp2c1
14
0.236
0.103
0.828
7.87E−05
2.13E−02

Mmp12
14
0.097
0.214
−0.837
7.92E−05
2.14E−02

Ntpcr
14
0.166
0.274
−0.631
8.29E−05
2.22E−02

Cd209a
14
0.436
0.622
−0.315
8.53E−05
2.28E−02

Slc25a33
14
0.154
0.247
−0.661
1.07E−04
2.75E−02

Smim3
14
0.568
0.606
−0.317
1.09E−04
2.81E−02

Nfkbia
14
0.896
0.775
0.243
1.12E−04
2.87E−02

Baiap2
14
0.197
0.308
−0.610
1.16E−04
2.97E−02

Atf4
14
0.672
0.654
−0.231
1.18E−04
3.01E−02

Cd300a
14
0.571
0.635
−0.305
1.24E−04
3.14E−02

Csnk2b
14
0.591
0.435
0.458
1.26E−04
3.19E−02

Mgl2
14
0.212
0.173
0.811
1.34E−04
3.36E−02

Dnase1l3
14
0.232
0.365
−0.624
1.37E−04
3.41E−02

Arih1
14
0.32
0.396
−0.585
1.40E−04
3.46E−02

Serpinb1a
14
0.224
0.088
0.860
1.44E−04
3.55E−02

Cd7
14
0.351
0.249
0.893
1.45E−04
3.56E−02

Csf2rb
14
0.436
0.573
−0.453
1.51E−04
3.68E−02

Fndc5
14
0.151
0.252
−0.668
1.52E−04
3.70E−02

Tspan13
14
0.745
0.814
−0.189
1.56E−04
3.78E−02

Tifab
14
0.228
0.319
−0.483
1.59E−04
3.84E−02

Rnf149
14
0.625
0.7
−0.352
1.75E−04
4.16E−02

Ccl3
14
0.174
0.077
1.191
1.75E−04
4.18E−02

St13
14
0.614
0.418
0.430
1.85E−04
4.35E−02

Pglyrp1
14
0.398
0.245
0.794
1.97E−04
4.60E−02

Gsdmd
14
0.228
0.147
0.638
2.13E−04
4.94E−02

Sla
15
0.617
0.335
0.970
3.56E−64
1.15E−59

Jund
15
0.797
0.928
−0.492
2.47E−59
5.13E−55

Klf4
15
0.104
0.319
−1.292
2.04E−46
2.47E−42

Dusp1
15
0.492
0.729
−0.680
1.33E−45
1.49E−41

Btg2
15
0.779
0.897
−0.347
5.17E−33
3.27E−29

Fosb
15
0.212
0.416
−0.826
5.80E−33
3.63E−29

Pim1
15
0.406
0.576
−0.561
3.11E−26
1.29E−22

Kdm6b
15
0.315
0.496
−0.670
7.03E−25
2.62E−21

Irf7
15
0.06
0.176
−1.344
1.60E−23
5.23E−20

Junb
15
0.938
0.982
−0.162
3.33E−23
1.05E−19

Bcl2
15
0.434
0.288
0.691
1.02E−22
3.14E−19

Igkc
15
0.967
0.933
0.581
1.53E−22
4.65E−19

Hk2
15
0.158
0.283
−0.866
1.65E−21
4.65E−18

Ptpn22
15
0.473
0.305
0.582
1.12E−20
3.02E−17

Pnrc1
15
0.506
0.648
−0.383
1.20E−20
3.21E−17

Fos
15
0.627
0.765
−0.368
3.15E−20
8.25E−17

Ppp1r15a
15
0.183
0.323
−0.710
4.02E−19
9.44E−16

Phlda1
15
0.157
0.287
−0.769
1.45E−18
3.24E−15

Srgn
15
0.568
0.422
0.478
7.07E−18
1.46E−14

Zfp36l2
15
0.364
0.219
0.671
8.48E−18
1.74E−14

Prr7
15
0.08
0.19
−0.972
1.57E−17
3.13E−14

Rsrp1
15
0.299
0.421
−0.508
2.68E−17
5.24E−14

Igha
15
0.905
0.83
0.540
5.48E−16
9.49E−13

Iglc1
15
0.104
0.217
−0.765
6.61E−16
1.14E−12

Hsp90aa1
15
0.283
0.163
0.761
7.31E−16
1.25E−12

Vps37b
15
0.387
0.497
−0.461
8.21E−16
1.39E−12

Emb
15
0.563
0.676
−0.344
1.93E−15
3.16E−12

Cxcr6
15
0.651
0.512
0.363
2.72E−15
4.45E−12

Klrk1
15
0.319
0.446
−0.502
2.95E−15
4.79E−12

Slc7a6os
15
0.074
0.16
−0.957
6.70E−15
1.04E−11

Ifrd1
15
0.195
0.304
−0.605
1.36E−14
2.05E−11

Tgif1
15
0.263
0.391
−0.476
4.15E−14
5.91E−11

Tnfaip3
15
0.31
0.44
−0.457
7.00E−14
9.75E−11

Rgcc
15
0.238
0.14
0.905
9.36E−14
1.28E−10

Pabpc1
15
0.486
0.574
−0.348
2.94E−13
3.80E−10

BC031181
15
0.293
0.376
−0.437
3.22E−13
4.13E−10

Il22
15
0.119
0.211
−1.132
4.47E−13
5.66E−10

Ikzf2
15
0.26
0.335
−0.468
2.23E−12
2.64E−09

Rasl11a
15
0.225
0.13
0.776
3.43E−12
3.93E−09

4930523C07Rik
15
0.196
0.284
−0.548
5.47E−12
6.12E−09

Cd69
15
0.371
0.49
−0.392
5.61E−12
6.27E−09

Dok1
15
0.18
0.086
0.749
1.82E−11
1.93E−08

Actg1
15
0.675
0.591
0.327
1.45E−10
1.37E−07

Sqstm1
15
0.205
0.274
−0.446
1.83E−10
1.70E−07

Gimap1
15
0.403
0.287
0.434
2.95E−10
2.66E−07

Ptp4a2
15
0.31
0.409
−0.387
3.33E−10
2.97E−07

Maff
15
0.382
0.456
−0.358
3.93E−10
3.42E−07

Ubb
15
0.85
0.837
−0.164
1.26E−09
1.02E−06

Btg1
15
0.778
0.832
−0.196
1.30E−09
1.04E−06

Icos
15
0.169
0.25
−0.490
4.08 E−09
2.98E−06

Fcer1g
15
0.714
0.606
0.250
5.49E−09
3.93E−06

Slc3a2
15
0.308
0.21
0.482
6.20E−09
4.42E−06

Il2rg
15
0.43
0.508
−0.294
7.60E−09
5.32E−06

Uhrf2
15
0.335
0.429
−0.336
8.61E−09
5.97E−06

Sepp1
15
0.639
0.689
−0.213
1.11E−08
7.59E−06

Nfkb1
15
0.162
0.247
−0.489
1.53E−08
1.02E−05

Sdhaf1
15
0.239
0.147
0.471
1.57E−08
1.05E−05

Txk
15
0.336
0.425
−0.354
1.83E−08
1.21E−05

Gimap5
15
0.277
0.184
0.508
1.85E−08
1.22E−05

Mmd
15
0.206
0.122
0.613
2.05E−08
1.34E−05

Gatad1
15
0.098
0.151
−0.587
3.89E−08
2.39E−05

Gpr157
15
0.161
0.086
0.658
3.97E−08
2.44E−05

Ncoa7
15
0.388
0.281
0.372
4.04E−08
2.47E−05

Nfkbia
15
0.488
0.583
−0.217
4.79E−08
2.89E−05

Bhlhe40
15
0.428
0.512
−0.275
5.09E−08
3.06E−05

Zc3h12a
15
0.146
0.215
−0.484
8.73E−08
5.01E−05

Tmem176a
15
0.554
0.465
0.304
1.11E−07
6.27E−05

Ptp4a1
15
0.152
0.202
−0.423
1.23E−07
6.90E−05

Ffar2
15
0.307
0.219
0.436
1.42E−07
7.92E−05

Fam110a
15
0.128
0.195
−0.569
2.16E−07
1.16E−04

Saraf
15
0.267
0.331
−0.335
2.39E−07
1.27E−04

Gpr171
15
0.193
0.119
0.561
3.35E−07
1.73E−04

Gem
15
0.442
0.498
−0.291
6.28E−07
3.06E−04

Zfp36l1
15
0.797
0.734
0.223
7.29E−07
3.48E−04

Tgoln1
15
0.171
0.22
−0.390
7.70E−07
3.66E−04

Abhd2
15
0.26
0.351
−0.399
8.29E−07
3.92E−04

Clcn3
15
0.159
0.222
−0.424
1.02E−06
4.72E−04

Lgals3
15
0.529
0.572
−0.219
1.19E−06
5.41E−04

H2-K1
15
0.593
0.622
−0.181
1.25E−06
5.67E−04

Nr4a3
15
0.176
0.106
0.618
1.38E−06
6.15E−04

Ahr
15
0.183
0.111
0.510
1.82E−06
7.92E−04

Tmem176b
15
0.612
0.517
0.252
2.19E−06
9.28E−04

Nfkbiz
15
0.183
0.244
−0.394
2.22E−06
9.41E−04

Litaf
15
0.247
0.165
0.430
2.65E−06
1.09E−03

Gimap9
15
0.158
0.095
0.576
2.96E−06
1.21E−03

Clk1
15
0.296
0.364
−0.309
3.26E−06
1.31E−03

B930036N10Rik
15
0.107
0.153
−0.603
3.47E−06
1.39E−03

Mast4
15
0.166
0.219
−0.371
3.57E−06
1.42E−03

Gltscr2
15
0.354
0.408
−0.254
4.91E−06
1.89E−03

Slc25a3
15
0.224
0.286
−0.333
5.24E−06
2.01E−03

Asb2
15
0.183
0.238
−0.386
6.86E−06
2.55E−03

Orai1
15
0.155
0.093
0.486
8.96E−06
3.23E−03

Ubald2
15
0.13
0.173
−0.455
9.14E−06
3.29E−03

Pcbp2
15
0.361
0.419
−0.234
9.64E−06
3.45E−03

Fam107b
15
0.186
0.118
0.509
1.09E−05
3.83E−03

Xlr4c
15
0.146
0.195
−0.381
1.18E−05
4.12E−03

Srsf5
15
0.48
0.538
−0.179
1.23E−05
4.28E−03

AW112010
15
0.776
0.706
0.183
1.26E−05
4.35E−03

Dusp5
15
0.329
0.408
−0.257
1.41E−05
4.81E−03

Hspe1
15
0.253
0.178
0.384
1.69E−05
5.65E−03

Mapkapk2
15
0.162
0.1
0.528
1.74E−05
5.78E−03

Cd7
15
0.397
0.314
0.305
1.79E−05
5.93E−03

Ccnl1
15
0.2
0.252
−0.331
1.98E−05
6.48E−03

Nfkbid
15
0.15
0.212
−0.427
2.15E−05
6.95E−03

Prdx2
15
0.165
0.104
0.451
2.23E−05
7.14E−03

Tnfsf11
15
0.204
0.135
0.422
2.38E−05
7.60E−03

Ybx1
15
0.43
0.493
−0.206
2.58E−05
8.13E−03

Actb
15
0.881
0.917
−0.206
3.83E−05
1.15E−02

Samsn1
15
0.334
0.252
0.264
4.01E−05
1.19E−02

Hspa8
15
0.619
0.566
0.228
4.14E−05
1.23E−02

Lcp1
15
0.399
0.321
0.335
4.25E−05
1.26E−02

Dhrs3
15
0.224
0.155
0.385
4.92E−05
1.42E−02

Kit
15
0.295
0.337
−0.236
5.11E−05
1.47E−02

Cox17
15
0.349
0.282
0.293
5.34E−05
1.53E−02

Ppm1h
15
0.101
0.151
−0.498
6.23E−05
1.75E−02

Gna13
15
0.203
0.254
−0.319
6.38E−05
1.78E−02

Egr1
15
0.17
0.112
0.477
6.39E−05
1.78E−02

Ccng2
15
0.143
0.194
−0.396
7.04E−05
1.94E−02

Tmem59
15
0.368
0.286
0.266
7.78E−05
2.11E−02

Nabp1
15
0.355
0.422
−0.242
8.55E−05
2.28E−02

Pfdn5
15
0.603
0.523
0.204
9.03E−05
2.39E−02

Selplg
15
0.504
0.433
0.275
9.18E−05
2.42E−02

H2-Q7
15
0.13
0.166
−0.354
9.97E−05
2.59E−02

Spop
15
0.14
0.191
−0.355
1.04E−04
2.70E−02

Serp1
15
0.224
0.275
−0.272
1.06E−04
2.75E−02

Ptprcap
15
0.327
0.252
0.323
1.08E−04
2.77E−02

Ier5
15
0.25
0.313
−0.262
1.23E−04
3.12E−02

Calm2
15
0.41
0.444
−0.186
1.25E−04
3.16E−02

Coq10b
15
0.192
0.255
−0.308
1.35E−04
3.37E−02

Kcnk1
15
0.22
0.158
0.396
1.37E−04
3.40E−02

Zap70
15
0.243
0.182
0.350
1.38E−04
3.43E−02

C4b
15
0.227
0.161
0.410
1.51E−04
3.68E−02

Rbm3
15
0.414
0.458
−0.186
1.53E−04
3.72E−02

Eif4a1
15
0.404
0.437
−0.177
1.56E−04
3.77E−02

Tmed2
15
0.296
0.348
−0.228
1.56E−04
3.78E−02

Hsp90ab1
15
0.363
0.31
0.316
1.84E−04
4.35E−02

Dph3
15
0.137
0.175
−0.315
2.00E−04
4.67E−02

Gm2a
15
0.226
0.279
−0.336
2.01E−04
4.69E−02

Rsrp1
16
0.328
0.676
−1.081
6.67E−08
3.91E−05

Btg2
16
0.681
0.901
−0.858
8.99E−08
5.14E−05

Traf1
16
0.138
0.341
−0.795
1.19E−04
3.04E−02

H2-D1
16
0.94
0.951
−0.358
1.71E−04
4.10E−02

Pnrc1
16
0.25
0.577
−0.914
1.92E−04
4.50E−02

Ifngr1
17
0.267
0.857
−1.121
1.01E−04
2.62E−02

Cd28
19
0.588
0.458
−0.588
2.92E−06
1.19E−03

Cd74
19
0.118
0.5
−0.250
9.75E−06
3.48E−03

Trbc1
19
0.706
0.333
2.193
1.69E−05
5.65E−03

Igkv1-135
2
0.004
0.175
−3.217
6.34E−08
3.74E−05

Fosl2
2
0.032
0.175
−1.947
2.21E−05
7.10E−03

Nr4a2
2
0.035
0.175
−2.145
4.72E−05
1.38E−02

Gapdh
2
0.603
0.54
0.677
1.04E−04
2.69E−02

Txnip
20
0.205
0.582
−1.669
1.31E−184
7.60E−179

Mcpt1
20
0.252
0.02
2.731
7.68E−163
2.23E−157

Igkv1-135
20
0.091
0.365
−1.523
1.15E−110
1.67E−105

Mcpt2
20
0.159
0.007
3.011
5.12E−109
5.96E−104

Ighg1
20
0.381
0.13
2.328
2.92E−108
2.83E−103

Igkv12-44
20
0.243
0.072
1.451
3.22E−88
2.68E−83

Ifi27l2a
20
0.354
0.622
−1.074
1.90E−84
1.10E−79

Ubald2
20
0.484
0.734
−0.802
1.92E−82
1.01E−77

Cacna1s
20
0.419
0.695
−0.890
5.33E−79
2.59E−74

Sepp1
20
0.235
0.501
−0.909
6.73E−77
3.01E−72

Pdia6
20
0.767
0.833
0.189
5.39E−64
1.65E−59

Rilpl2
20
0.48
0.686
−0.725
2.17E−63
6.31E−59

Iglc2
20
0.892
0.96
−0.559
1.71E−62
4.32E−58

Dusp5
20
0.402
0.65
−0.790
8.28E−62
1.93E−57

Fosb
20
0.527
0.761
−0.671
5.45E−60
1.22E−55

Serp1
20
0.88
0.975
−0.376
5.65E−60
1.22E−55

Grasp
20
0.091
0.269
−1.223
1.80E−55
3.37E−51

Ccr10
20
0.711
0.681
0.296
5.19E−55
9.15E−51

Ddit4
20
0.174
0.058
1.315
2.50E−53
4.15E−49

Malat1
20
0.976
0.99
−0.406
9.30E−53
1.46E−48

Pim1
20
0.767
0.916
−0.469
5.00E−49
6.93E−45

Hsp90b1
20
0.896
0.96
0.166
1.25E−46
1.55E−42

Trf
20
0.566
0.779
−0.516
3.72E−46
4.32E−42

Ifi27
20
0.102
0.273
−1.059
2.93E−45
3.22E−41

Odc1
20
0.297
0.485
−0.890
3.02E−44
3.14E−40

Xbp1
20
0.862
0.962
−0.460
3.30E−44
3.37E−40

Rgcc
20
0.18
0.372
−0.945
5.83E−44
5.85E−40

Nrip1
20
0.281
0.507
−0.727
3.65E−42
3.48E−38

Cd274
20
0.175
0.355
−0.938
8.53E−42
8.00E−38

Eif1
20
0.902
0.979
−0.352
3.22E−41
2.93E−37

Chac1
20
0.042
0.165
−1.345
4.88E−40
4.24E−36

Gmfg
20
0.204
0.113
0.842
2.80E−39
2.36E−35

Ly6a
20
0.052
0.173
−1.632
1.26E−38
1.02E−34

Pycard
20
0.669
0.725
0.345
6.97E−38
5.48E−34

Iglc1
20
0.831
0.956
−0.986
8.37E−38
6.50E−34

Actg1
20
0.624
0.633
0.359
2.29E−37
1.73E−33

Lmna
20
0.094
0.233
−1.156
5.66E−37
4.22E−33

Mdh1
20
0.535
0.505
0.218
3.80E−35
2.63E−31

Trib1
20
0.3
0.494
−0.641
4.86E−35
3.33E−31

Coro1a
20
0.534
0.513
0.294
7.57E−35
5.12E−31

Fth1
20
0.835
0.96
−0.389
1.87E−34
1.25E−30

Ifitm3
20
0.221
0.396
−0.837
1.27E−32
7.64E−29

Ly6d
20
0.307
0.499
−0.610
1.21E−31
6.96E−28

Cdc42
20
0.601
0.587
0.173
1.82E−31
1.03E−27

Ahnak
20
0.13
0.274
−0.857
2.40E−31
1.34E−27

Clic4
20
0.322
0.513
−0.601
6.74E−31
3.74E−27

Iglc3
20
0.8
0.938
−1.260
7.73E−31
4.20E−27

Zfp36l2
20
0.37
0.292
0.651
1.30E−30
6.93E−27

Mtdh
20
0.65
0.847
−0.428
1.89E−30
1.00E−26

Atf4
20
0.537
0.711
−0.482
6.56E−30
3.32E−26

Rpn1
20
0.548
0.565
0.164
3.86E−29
1.92E−25

Hsp90aa1
20
0.371
0.343
0.506
4.23E−28
2.02E−24

Fkbp11
20
0.542
0.549
0.240
4.27E−28
2.02E−24

Pkm
20
0.53
0.547
0.177
4.79E−28
2.23E−24

Txndc5
20
0.912
0.977
−0.302
1.02E−27
4.58E−24

5031425E22Rik
20
0.319
0.487
−0.660
1.51E−27
6.75E−24

Ralgds
20
0.079
0.195
−0.829
1.84E−26
7.80E−23

Vps37b
20
0.078
0.196
−0.936
2.42E−26
1.02E−22

Zfp706
20
0.689
0.852
−0.388
3.43E−26
1.41E−22

Eif4ebp1
20
0.149
0.279
−0.838
4.71E−26
1.92E−22

Il10rb
20
0.181
0.316
−0.652
5.08E−26
2.05E−22

Mcl1
20
0.505
0.683
−0.512
7.71E−26
3.05E−22

Ifnar2
20
0.216
0.359
−0.632
1.85E−25
7.18E−22

Tmem154
20
0.256
0.429
−0.595
2.32E−25
8.89E−22

Eno1
20
0.278
0.22
0.377
6.47E−25
2.43E−21

Ccser2
20
0.199
0.344
−0.660
1.25E−24
4.54E−21

Gm
20
0.2
0.373
−0.547
1.41E−24
5.09E−21

Taldo1
20
0.497
0.488
0.159
1.59E−24
5.73E−21

Ost4
20
0.756
0.895
−0.347
2.35E−24
8.39E−21

Ifi30
20
0.201
0.133
0.502
2.46E−24
8.72E−21

Bst2
20
0.546
0.71
−0.454
2.90E−24
1.02E−20

Igkv3-7
20
0.183
0.1
0.872
3.30E−24
1.16E−20

Slc7a5
20
0.125
0.259
−0.798
8.26E−24
2.83E−20

Kcnmb4os2
20
0.224
0.382
−0.548
1.35E−23
4.47E−20

Ptprcap
20
0.545
0.528
0.192
1.47E−23
4.82E−20

Ifnar1
20
0.139
0.27
−0.725
1.83E−23
5.92E−20

Plac8
20
0.119
0.252
−0.724
2.61E−23
8.29E−20

Ly6c1
20
0.858
0.94
−0.411
3.92E−23
1.22E−19

Tnfrsf13b
20
0.562
0.75
−0.406
6.67E−23
2.07E−19

Uqcrc1
20
0.477
0.459
0.175
2.42E−22
7.19E−19

Gimap5
20
0.306
0.461
−0.561
3.33E−22
9.85E−19

Ssbp1
20
0.254
0.378
−0.558
3.79E−22
1.11E−18

Prg2
20
0.147
0.293
−0.555
3.92E−22
1.15E−18

Peli1
20
0.273
0.423
−0.593
4.10E−22
1.19E−18

Ftl1
20
0.942
0.991
−0.270
4.52E−22
1.31E−18

Limd2
20
0.509
0.685
−0.439
1.09E−21
3.12E−18

Bckdk
20
0.399
0.589
−0.476
1.60E−21
4.51E−18

Nfkbia
20
0.691
0.829
−0.460
6.97E−21
1.90E−17

Saraf
20
0.421
0.579
−0.444
1.89E−20
4.99E−17

Ly6c2
20
0.909
0.967
−0.370
2.15E−20
5.67E−17

Fxyd5
20
0.499
0.468
0.193
3.27E−20
8.49E−17

P2rx4
20
0.136
0.263
−0.715
4.18E−20
1.07E−16

Cd69
20
0.557
0.755
−0.375
5.37E−20
1.37E−16

Ppp1r15a
20
0.372
0.508
−0.541
5.72E−20
1.45E−16

Ifrd1
20
0.202
0.351
−0.601
7.49E−20
1.89E−16

Itgb7
20
0.507
0.503
0.210
8.04E−20
2.02E−16

Irf7
20
0.075
0.173
−0.969
1.00E−19
2.49E−16

Clic1
20
0.367
0.339
0.257
1.35E−19
3.28E−16

Sepw1
20
0.835
0.942
−0.289
3.77E−19
8.92E−16

Cirbp
20
0.334
0.499
−0.454
3.82E−19
9.01E−16

Skil
20
0.354
0.516
−0.443
5.85E−19
1.35E−15

Nfkb2
20
0.123
0.229
−0.681
1.60E−18
3.54E−15

Tmed2
20
0.786
0.936
−0.322
2.01E−18
4.41E−15

Mthfd2
20
0.139
0.262
−0.725
2.09E−18
4.56E−15

Trp53i11
20
0.271
0.421
−0.527
2.52E−18
5.43E−15

Cybb
20
0.421
0.581
−0.445
5.99E−18
1.25E−14

Cebpg
20
0.17
0.27
−0.597
9.54E−18
1.95E−14

Hist1h2ap
20
0.165
0.13
0.704
1.11E−17
2.24E−14

Ccng2
20
0.185
0.309
−0.592
1.30E−17
2.60E−14

S100a10
20
0.355
0.321
0.361
1.83E−17
3.60E−14

Ctss
20
0.493
0.658
−0.370
3.29E−17
6.36E−14

Pou2f1
20
0.103
0.207
−0.733
4.59E−17
8.75E−14

Dusp4
20
0.119
0.217
−0.870
5.91E−17
1.11E−13

Rrad
20
0.165
0.261
−0.972
6.96E−17
1.29E−13

Sdc1
20
0.726
0.857
−0.341
8.01E−17
1.47E−13

Pcbp2
20
0.585
0.758
−0.388
8.14E−17
1.49E−13

Junb
20
0.514
0.686
−0.400
1.46E−16
2.64E−13

Cd48
20
0.319
0.286
0.218
1.91E−16
3.41E−13

Rbm7
20
0.299
0.421
−0.465
1.98E−16
3.53E−13

Vim
20
0.254
0.215
0.525
2.46E−16
4.37E−13

Zbp1
20
0.302
0.433
−0.472
2.67E−16
4.71E−13

Prkcsh
20
0.267
0.223
0.244
3.33E−16
5.88E−13

Polr2m
20
0.258
0.41
−0.544
5.09E−16
8.89E−13

Crem
20
0.186
0.303
−0.549
5.43E−16
9.43E−13

Serpina3g
20
0.078
0.171
−0.805
6.85E−16
1.17E−12

Cd79a
20
0.83
0.935
−0.268
1.69E−15
2.81E−12

Pink1
20
0.29
0.43
−0.454
1.80E−15
2.97E−12

Kctd12
20
0.185
0.307
−0.609
1.88E−15
3.10E−12

Ypel3
20
0.394
0.562
−0.391
2.91E−15
4.72E−12

Elf1
20
0.292
0.404
−0.469
3.95E−15
6.32E−12

Smap2
20
0.254
0.397
−0.512
4.54E−15
7.20E−12

Jtb
20
0.456
0.61
−0.370
4.65E−15
7.33E−12

Tram1
20
0.708
0.86
−0.340
5.23E−15
8.18E−12

A530040E14Rik
20
0.465
0.619
−0.421
6.80E−15
1.05E−11

P2ry10
20
0.108
0.206
−0.645
8.23E−15
1.27E−11

Pls1
20
0.14
0.243
−0.573
1.11E−14
1.70E−11

Srsf9
20
0.453
0.606
−0.409
1.32E−14
2.00E−11

Hmgn3
20
0.373
0.502
−0.399
1.82E−14
2.72E−11

AC125149.3
20
0.449
0.624
−0.432
1.82E−14
2.72E−11

Idh3g
20
0.312
0.286
0.185
2.25E−14
3.35E−11

H3f3b
20
0.873
0.976
−0.345
2.30E−14
3.41E−11

Pqlc3
20
0.48
0.629
−0.390
2.65E−14
3.89E−11

Psmc4
20
0.269
0.232
0.193
2.69E−14
3.94E−11

Tyrobp
20
0.144
0.252
−0.592
2.99E−14
4.36E−11

Hist1h4i
20
0.293
0.249
0.394
3.01E−14
4.38E−11

Filip1l
20
0.121
0.221
−0.625
3.48E−14
5.03E−11

B2m
20
0.965
0.984
−0.278
3.56E−14
5.13E−11

Irf8
20
0.087
0.173
−0.833
3.80E−14
5.44E−11

D16Ertd472e
20
0.142
0.24
−0.595
4.87E−14
6.90E−11

Dyrk3
20
0.088
0.166
−0.777
5.10E−14
7.20E−11

Jund
20
0.875
0.978
−0.243
5.84E−14
8.21E−11

AW112010
20
0.287
0.443
−0.396
6.42E−14
8.98E−11

Jchain
20
0.993
0.991
−0.214
9.15E−14
1.25E−10

Ormdl3
20
0.156
0.265
−0.550
9.16E−14
1.25E−10

Nacc2
20
0.264
0.41
−0.454
1.05E−13
1.42E−10

Ldha
20
0.344
0.331
0.166
1.09E−13
1.47E−10

Al413582
20
0.283
0.407
−0.451
1.47E−13
1.96E−10

Agpat4
20
0.174
0.281
−0.579
1.50E−13
2.00E−10

Slc39a7
20
0.465
0.624
−0.389
1.86E−13
2.46E−10

Cdv3
20
0.565
0.702
−0.359
2.36E−13
3.10E−10

Tgif1
20
0.109
0.199
−0.659
2.49E−13
3.27E−10

Bcl10
20
0.251
0.368
−0.464
2.56E−13
3.34E−10

Arid5a
20
0.079
0.154
−0.725
2.85E−13
3.70E−10

Shisa5
20
0.824
0.936
−0.287
2.91E−13
3.77E−10

Rheb
20
0.409
0.547
−0.420
3.02E−13
3.89E−10

Ring1
20
0.117
0.214
−0.648
3.68E−13
4.70E−10

Med25
20
0.126
0.19
−0.712
4.62E−13
5.83E−10

Aes
20
0.463
0.62
−0.371
7.23E−13
8.99E−10

Hmgb2
20
0.272
0.307
0.336
1.06E−12
1.30E−09

Tmem184b
20
0.093
0.18
−0.634
1.12E−12
1.37E−09

Insl6
20
0.186
0.292
−0.482
1.28E−12
1.56E−09

Siah2
20
0.235
0.358
−0.461
1.29E−12
1.57E−09

Reep3
20
0.132
0.235
−0.574
1.35E−12
1.63E−09

Ergic1
20
0.334
0.485
−0.461
1.61E−12
1.94E−09

Sumo3
20
0.206
0.327
−0.531
1.95E−12
2.33E−09

Azin1
20
0.33
0.473
−0.426
2.08E−12
2.47E−09

Psmc2
20
0.24
0.203
0.230
2.25E−12
2.67E−09

Pnrc1
20
0.607
0.767
−0.334
2.26E−12
2.67E−09

Rab3d
20
0.162
0.267
−0.517
2.34E−12
2.75E−09

Cd93
20
0.137
0.24
−0.527
2.87E−12
3.35E−09

Gramd3
20
0.147
0.249
−0.495
2.88E−12
3.36E−09

Lbh
20
0.177
0.283
−0.502
2.97E−12
3.45E−09

Arl4a
20
0.124
0.221
−0.585
2.98E−12
3.46E−09

Ctso
20
0.212
0.331
−0.480
3.32E−12
3.82E−09

Ier5
20
0.515
0.665
−0.365
3.43E−12
3.93E−09

VgIl4
20
0.142
0.238
−0.587
5.08E−12
5.73E−09

Map7d1
20
0.203
0.313
−0.465
5.28E−12
5.94E−09

Usf1
20
0.138
0.226
−0.559
5.34E−12
6.00E−09

Tmem123
20
0.52
0.686
−0.333
5.40E−12
6.05E−09

Ctsa
20
0.263
0.225
0.220
6.34E−12
7.05E−09

Ginm1
20
0.181
0.281
−0.479
6.54E−12
7.26E−09

Tmsb4x
20
0.9
0.945
0.168
7.61E−12
8.41E−09

Vmp1
20
0.346
0.481
−0.432
8.85E−12
9.68E−09

Dnajb9
20
0.487
0.653
−0.360
9.38E−12
1.02E−08

Man1b1
20
0.334
0.478
−0.422
9.99E−12
1.08E−08

Rassf3
20
0.109
0.178
−0.553
1.12E−11
1.21E−08

Tpst1
20
0.178
0.288
−0.523
1.14E−11
1.23E−08

Copb2
20
0.267
0.24
0.214
1.25E−11
1.34E−08

Ube2d3
20
0.651
0.818
−0.333
1.48E−11
1.58E−08

Cnn2
20
0.202
0.175
0.293
1.51E−11
1.61E−08

Eif4a2
20
0.459
0.616
−0.370
1.53E−11
1.62E−08

Tmem192
20
0.249
0.372
−0.444
1.96E−11
2.07E−08

Sec11c
20
0.898
0.972
−0.233
2.74E−11
2.86E−08

Casp4
20
0.202
0.309
−0.472
2.87E−11
2.97E−08

St6gal1
20
0.583
0.738
−0.339
3.02E−11
3.11E−08

Kdm2b
20
0.1
0.186
−0.646
3.10E−11
3.19E−08

Ckb
20
0.179
0.141
0.331
3.72E−11
3.81E−08

Scand1
20
0.513
0.651
−0.340
4.15E−11
4.22E−08

Rab28
20
0.124
0.213
−0.548
4.19E−11
4.26E−08

Bmi1
20
0.095
0.179
−0.579
4.52E−11
4.57E−08

Cers2
20
0.319
0.443
−0.412
4.80E−11
4.82E−08

Sdha
20
0.255
0.22
0.151
5.60E−11
5.59E−08

Vapa
20
0.403
0.547
−0.378
6.08E−11
6.05E−08

Stoml1
20
0.091
0.163
−0.634
6.48E−11
6.43E−08

Idnk
20
0.277
0.393
−0.387
7.20E−11
7.11E−08

Tmem219
20
0.309
0.44
−0.399
8.75E−11
8.51E−08

Commd3
20
0.317
0.448
−0.400
9.50E−11
9.18E−08

Kif5b
20
0.356
0.5
−0.423
1.17E−10
1.12E−07

Klhdc1
20
0.083
0.154
−0.601
1.81E−10
1.69E−07

Pml
20
0.184
0.284
−0.515
1.85E−10
1.72E−07

Tcf4
20
0.42
0.551
−0.385
1.87E−10
1.74E−07

Tram2
20
0.287
0.426
−0.395
2.12E−10
1.95E−07

Ppp1r11
20
0.404
0.535
−0.368
2.34E−10
2.14E−07

Smim19
20
0.123
0.201
−0.511
2.40E−10
2.19E−07

Limd1
20
0.164
0.256
−0.529
3.52E−10
3.13E−07

Cd200
20
0.428
0.595
−0.279
3.54E−10
3.14E−07

PigP
20
0.142
0.217
−0.492
3.88E−10
3.38E−07

A630072M18Rik
20
0.085
0.16
−0.686
4.35E−10
3.77E−07

Pabpc1
20
0.708
0.867
−0.300
5.39E−10
4.66E−07

Orai1
20
0.151
0.233
−0.466
8.79E−10
7.39E−07

Spg21
20
0.176
0.276
−0.489
9.10E−10
7.62E−07

Actb
20
0.953
0.968
0.250
9.34E−10
7.80E−07

Ddrgk1
20
0.533
0.672
−0.321
9.80E−10
8.16E−07

Cebpb
20
0.27
0.382
−0.374
1.06E−09
8.76E−07

Hiat1
20
0.132
0.204
−0.490
1.06E−09
8.76E−07

Ubxn6
20
0.201
0.296
−0.426
1.07E−09
8.78E−07

Fam214a
20
0.228
0.346
−0.415
1.10E−09
9.05E−07

Stub1
20
0.22
0.33
−0.454
1.33E−09
1.07E−06

Chtf8
20
0.09
0.154
−0.560
1.41E−09
1.13E−06

Fcer1g
20
0.293
0.407
−0.335
1.51E−09
1.21E−06

Plbd2
20
0.156
0.251
−0.479
1.69E−09
1.34E−06

Drap1
20
0.285
0.392
−0.390
1.74E−09
1.38E−06

1500011B03Rik
20
0.166
0.257
−0.506
1.75E−09
1.38E−06

Gpx4
20
0.626
0.759
−0.299
1.94E−09
1.52E−06

Gng5
20
0.572
0.709
−0.307
1.94E−09
1.52E−06

Bcl2l11
20
0.269
0.369
−0.489
1.96E−09
1.53E−06

Cflar
20
0.222
0.328
−0.458
1.98E−09
1.55E−06

Ddx39
20
0.169
0.142
0.237
2.16E−09
1.68E−06

Tspan13
20
0.744
0.886
−0.288
2.17E−09
1.68E−06

Ppp2r5a
20
0.332
0.453
−0.392
2.37E−09
1.84E−06

Lrrfip2
20
0.091
0.159
−0.580
2.38E−09
1.84E−06

EIl2
20
0.543
0.697
−0.344
2.41E−09
1.85E−06

Btg3
20
0.251
0.358
−0.417
2.42E−09
1.86E−06

Scamp3
20
0.126
0.209
−0.532
2.46E−09
1.89E−06

Ptp4a1
20
0.208
0.313
−0.448
2.76E−09
2.10E−06

Mettl1
20
0.278
0.383
−0.404
2.85E−09
2.16E−06

Relb
20
0.127
0.203
−0.501
2.90E−09
2.19E−06

Mxd1
20
0.126
0.207
−0.515
3.08E−09
2.31E−06

Bcl2
20
0.221
0.336
−0.342
3.47E−09
2.58E−06

Akirin1
20
0.293
0.408
−0.379
3.60E−09
2.67E−06

4930453N24Rik
20
0.111
0.159
−0.464
3.66E−09
2.70E−06

Nxf1
20
0.286
0.401
−0.389
4.18E−09
3.05E−06

Fam174a
20
0.181
0.274
−0.391
4.23E−09
3.07E−06

Rad23a
20
0.147
0.245
−0.460
4.23E−09
3.07E−06

Ptp4a2
20
0.666
0.82
−0.304
4.54E−09
3.29E−06

Rad23b
20
0.353
0.486
−0.376
4.99E−09
3.60E−06

Arrdc3
20
0.136
0.226
−0.504
5.05E−09
3.63E−06

Tsg101
20
0.193
0.297
−0.456
5.65E−09
4.04E−06

Blmh
20
0.177
0.148
0.173
6.02E−09
4.29E−06

H2-T22
20
0.165
0.249
−0.450
6.32E−09
4.49E−06

Uqcc2
20
0.365
0.504
−0.382
6.66E−09
4.73E−06

Tmem251
20
0.139
0.225
−0.487
6.79E−09
4.80E−06

Tor2a
20
0.313
0.425
−0.372
6.85E−09
4.84E−06

Sel1l
20
0.473
0.608
−0.346
7.02E−09
4.95E−06

Tmc6
20
0.169
0.247
−0.401
7.42E−09
5.22E−06

Psip1
20
0.341
0.469
−0.395
7.44E−09
5.22E−06

Btg1
20
0.208
0.313
−0.369
7.53E−09
5.28E−06

Gimap1
20
0.649
0.789
−0.305
7.54E−09
5.28E−06

Tuba1b
20
0.209
0.225
0.341
8.54E−09
5.93E−06

Cib2
20
0.126
0.195
−0.474
9.05E−09
6.24E−06

Tapbpl
20
0.276
0.4
−0.376
9.07E−09
6.25E−06

Smarca2
20
0.113
0.187
−0.560
9.48E−09
6.51E−06

Wnk1
20
0.26
0.357
−0.421
9.80E−09
6.73E−06

H2afj
20
0.583
0.73
−0.310
1.01E−08
6.88E−06

Ikzf3
20
0.167
0.263
−0.464
1.41E−08
9.43E−06

Zc3h14
20
0.133
0.218
−0.523
1.51E−08
1.01E−05

Lrp10
20
0.336
0.461
−0.368
1.73E−08
1.15E−05

Foxp1
20
0.218
0.313
−0.425
1.98E−08
1.30E−05

Rap1b
20
0.479
0.617
−0.343
2.06E−08
1.34E−05

Nfkbie
20
0.089
0.159
−0.540
2.07E−08
1.35E−05

Pkig
20
0.578
0.733
−0.314
2.08E−08
1.36E−05

Laptm5
20
0.422
0.56
−0.343
2.13E−08
1.39E−05

Mast4
20
0.129
0.2
−0.492
2.15E−08
1.40E−05

Cd83
20
0.106
0.184
−0.492
2.47E−08
1.59E−05

Dnajc7
20
0.582
0.713
−0.312
2.69E−08
1.72E−05

Gnl3
20
0.142
0.237
−0.503
2.92E−08
1.85E−05

Nudt18
20
0.252
0.35
−0.398
2.96E−08
1.87E−05

Rftn1
20
0.378
0.5
−0.347
3.03E−08
1.92E−05

1810043H04Rik
20
0.265
0.385
−0.384
3.09E−08
1.95E−05

Desi1
20
0.487
0.62
−0.330
3.28E−08
2.06E−05

Ppp1r2
20
0.211
0.311
−0.443
3.31E−08
2.07E−05

Napsa
20
0.202
0.171
0.207
3.51E−08
2.19E−05

Slc3a2
20
0.528
0.67
−0.297
3.59E−08
2.22E−05

Pfdn5
20
0.784
0.906
−0.267
3.67E−08
2.28E−05

Scarb2
20
0.189
0.284
−0.412
3.89E−08
2.39E−05

Sh3glb1
20
0.483
0.621
−0.334
4.12E−08
2.52E−05

Ddit3
20
0.181
0.275
−0.432
4.32E−08
2.63E−05

Cars
20
0.113
0.187
−0.508
4.65E−08
2.82E−05

4933434E20Rik
20
0.35
0.473
−0.366
4.78E−08
2.89E−05

Pcif1
20
0.248
0.358
−0.379
4.80E−08
2.89E−05

Tpst2
20
0.51
0.654
−0.309
5.01E−08
3.01E−05

Rab10
20
0.31
0.438
−0.364
5.12E−08
3.07E−05

Edem2
20
0.813
0.935
−0.257
5.31E−08
3.18E−05

Pofut2
20
0.137
0.216
−0.467
5.38E−08
3.22E−05

Mapkapk2
20
0.142
0.218
−0.459
5.38E−08
3.22E−05

Brcc3
20
0.163
0.138
0.202
5.90E−08
3.49E−05

Pex16
20
0.161
0.242
−0.386
6.63E−08
3.90E−05

Tpd52
20
0.128
0.207
−0.463
7.96E−08
4.60E−05

Anapc5
20
0.469
0.621
−0.357
8.19E−08
4.71E−05

Smc4
20
0.186
0.169
0.183
8.60E−08
4.94E−05

Arsg
20
0.092
0.153
−0.506
1.25E−07
7.00E−05

Ltb
20
0.183
0.259
−0.485
1.34E−07
7.50E−05

Ap3s1
20
0.402
0.505
−0.304
1.36E−07
7.60E−05

Hmg20b
20
0.123
0.192
−0.504
1.50E−07
8.34E−05

Rnf19b
20
0.172
0.264
−0.414
1.52E−07
8.39E−05

Ptpra
20
0.097
0.161
−0.511
1.55E−07
8.58E−05

Tm2d1
20
0.195
0.291
−0.423
1.65E−07
9.08E−05

Amfr
20
0.276
0.382
−0.349
1.66E−07
9.10E−05

Mgat2
20
0.54
0.669
−0.315
1.81E−07
9.86E−05

Ccz1
20
0.219
0.303
−0.410
1.87E−07
1.02E−04

Btf3l4
20
0.18
0.271
−0.397
1.92E−07
1.04E−04

Dnajc19
20
0.386
0.535
−0.346
1.93E−07
1.05E−04

Cyth2
20
0.161
0.242
−0.430
2.05E−07
1.11E−04

Ggta1
20
0.11
0.178
−0.538
2.15E−07
1.15E−04

Fam177a
20
0.103
0.173
−0.530
2.43E−07
1.29E−04

Bet1l
20
0.242
0.322
−0.349
2.48E−07
1.31E−04

Cdipt
20
0.238
0.34
−0.416
2.56E−07
1.35E−04

Zfp560
20
0.13
0.198
−0.422
2.67E−07
1.41E−04

Wipi1
20
0.23
0.329
−0.392
2.72E−07
1.43E−04

Ninj1
20
0.273
0.387
−0.364
2.77E−07
1.45E−04

Ndufaf4
20
0.092
0.16
−0.555
2.86E−07
1.50E−04

Rapgef1
20
0.133
0.207
−0.452
2.92E−07
1.53E−04

Ddx5
20
0.736
0.859
−0.266
2.94E−07
1.53E−04

Ddx54
20
0.233
0.334
−0.388
3.04E−07
1.58E−04

Ube2e3
20
0.264
0.374
−0.350
3.09E−07
1.60E−04

Eif5
20
0.587
0.732
−0.308
3.23E−07
1.67E−04

Hes1
20
0.2
0.274
−0.641
3.29E−07
1.70E−04

Tusc2
20
0.134
0.207
−0.465
3.31E−07
1.71E−04

Tiparp
20
0.249
0.358
−0.387
3.52E−07
1.80E−04

Gbp4
20
0.093
0.158
−0.519
3.90E−07
1.99E−04

Ankrd12
20
0.256
0.349
−0.361
4.18E−07
2.12E−04

Fastk
20
0.177
0.262
−0.425
4.21E−07
2.13E−04

Atg101
20
0.15
0.222
−0.439
4.38E−07
2.21E−04

Mdm2
20
0.214
0.303
−0.414
4.46E−07
2.24E−04

Tgfb1
20
0.228
0.308
−0.387
4.47E−07
2.25E−04

Bri3
20
0.211
0.31
−0.379
4.64E−07
2.33E−04

Stard5
20
0.16
0.254
−0.409
4.81E−07
2.41E−04

Irf4
20
0.348
0.479
−0.375
5.16E−07
2.57E−04

Upf3b
20
0.174
0.221
−0.309
5.18E−07
2.57E−04

Ubald1
20
0.17
0.246
−0.432
5.35E−07
2.65E−04

Rab3a
20
0.115
0.186
−0.511
5.46E−07
2.70E−04

Pck2
20
0.266
0.344
−0.325
5.60E−07
2.76E−04

Grina
20
0.337
0.444
−0.312
5.64E−07
2.78E−04

Dph3
20
0.356
0.479
−0.351
5.91E−07
2.90E−04

Eif4a3
20
0.221
0.203
0.151
5.94E−07
2.92E−04

Zc3h15
20
0.3
0.389
−0.352
5.98E−07
2.93E−04

Ppp3ca
20
0.262
0.364
−0.363
6.03E−07
2.95E−04

Clptm1l
20
0.651
0.788
−0.293
7.17E−07
3.44E−04

Dera
20
0.179
0.16
0.158
7.18E−07
3.44E−04

St8sia6
20
0.247
0.344
−0.382
7.19E−07
3.45E−04

Cited2
20
0.542
0.611
0.167
7.22E−07
3.45E−04

Sar1a
20
0.546
0.695
−0.306
7.28E−07
3.48E−04

Wipf1
20
0.121
0.199
−0.474
7.39E−07
3.53E−04

4930523C07Rik
20
0.307
0.411
−0.393
7.45E−07
3.55E−04

Mta2
20
0.256
0.34
−0.367
8.25E−07
3.90E−04

Ptpn6
20
0.268
0.375
−0.376
8.37E−07
3.95E−04

Pgrmc1
20
0.205
0.285
−0.376
8.69E−07
4.08 E−04

Fndc3a
20
0.324
0.425
−0.331
8.70E−07
4.08 E−04

Gtf3c6
20
0.181
0.166
0.189
9.88E−07
4.60E−04

Ccs
20
0.158
0.135
0.190
9.90E−07
4.61E−04

Lrrn3
20
0.099
0.156
−0.521
1.01E−06
4.66E−04

Tcf3
20
0.326
0.404
−0.300
1.10E−06
5.05E−04

Mob1a
20
0.1
0.159
−0.493
1.10E−06
5.07E−04

Setd3
20
0.132
0.207
−0.408
1.17E−06
5.33E−04

Sdc4
20
0.423
0.533
−0.265
1.17E−06
5.33E−04

Rp9
20
0.342
0.455
−0.351
1.17E−06
5.33E−04

Tomm20
20
0.408
0.529
−0.332
1.17E−06
5.33E−04

Vamp3
20
0.253
0.341
−0.366
1.19E−06
5.44E−04

Herpud2
20
0.121
0.177
−0.398
1.20E−06
5.45E−04

Dctn3
20
0.349
0.404
−0.287
1.27E−06
5.77E−04

Pitpnb
20
0.101
0.161
−0.517
1.29E−06
5.85E−04

Csnk1a1
20
0.34
0.437
−0.338
1.30E−06
5.89E−04

Dynlt3
20
0.261
0.348
−0.342
1.34E−06
6.01E−04

Arpc5l
20
0.444
0.588
−0.332
1.35E−06
6.05E−04

Atp6v1d
20
0.2
0.284
−0.371
1.37E−06
6.14E−04

Ccpg1
20
0.33
0.426
−0.263
1.40E−06
6.27E−04

Cytip
20
0.619
0.753
−0.297
1.54E−06
6.80E−04

Tmem147
20
0.413
0.54
−0.323
1.61E−06
7.11E−04

Isyna1
20
0.165
0.149
0.169
1.62E−06
7.12E−04

Bhlha15
20
0.213
0.309
−0.404
1.64E−06
7.19E−04

A930033H14Rik
20
0.104
0.165
−0.518
1.68E−06
7.39E−04

Vimp
20
0.72
0.846
−0.262
1.71E−06
7.50E−04

Asns
20
0.096
0.165
−0.481
1.74E−06
7.62E−04

Sp140
20
0.306
0.399
−0.342
1.75E−06
7.65E−04

Sumo1
20
0.442
0.58
−0.315
1.78E−06
7.76E−04

Toporsos
20
0.151
0.229
−0.459
1.78E−06
7.76E−04

March5
20
0.273
0.369
−0.354
1.88E−06
8.13E−04

Srpr
20
0.446
0.585
−0.309
1.90E−06
8.21E−04

Inpp1
20
0.119
0.186
−0.447
1.91E−06
8.25E−04

Emc6
20
0.288
0.383
−0.328
2.02E−06
8.62E−04

Spint2
20
0.64
0.764
−0.248
2.05E−06
8.76E−04

Fbxw2
20
0.183
0.261
−0.418
2.15E−06
9.16E−04

Atp6v0a1
20
0.253
0.352
−0.351
2.16E−06
9.16E−04

Myl12a
20
0.505
0.637
−0.314
2.26E−06
9.54E−04

Unc50
20
0.265
0.37
−0.356
2.31E−06
9.75E−04

Akap9
20
0.116
0.186
−0.471
2.33E−06
9.83E−04

Tmem248
20
0.615
0.767
−0.292
2.35E−06
9.91E−04

D8Ertd738e
20
0.503
0.657
−0.312
2.41E−06
1.01E−03

Stx7
20
0.132
0.205
−0.465
2.43E−06
1.02E−03

Rela
20
0.113
0.179
−0.447
2.45E−06
1.03E−03

Smim20
20
0.133
0.194
−0.424
2.49E−06
1.04E−03

Sod2
20
0.363
0.468
−0.313
2.50E−06
1.04E−03

Zfand5
20
0.23
0.328
−0.406
2.51E−06
1.05E−03

Atat1
20
0.397
0.525
−0.325
2.63E−06
1.09E−03

Vars
20
0.394
0.526
−0.346
2.72E−06
1.12E−03

Lrrc8d
20
0.14
0.21
−0.453
2.79E−06
1.15E−03

Ube2g2
20
0.14
0.214
−0.431
2.83E−06
1.16E−03

Ap4s1
20
0.185
0.245
−0.357
2.91E−06
1.19E−03

Arl2bp
20
0.216
0.295
−0.341
2.92E−06
1.19E−03

Ralbp1
20
0.332
0.445
−0.372
3.05E−06
1.23E−03

Dtx3
20
0.114
0.174
−0.431
3.07E−06
1.24E−03

Golga4
20
0.175
0.243
−0.373
3.13E−06
1.26E−03

Mia3
20
0.188
0.267
−0.399
3.14E−06
1.27E−03

Birc3
20
0.153
0.23
−0.368
3.14E−06
1.27E−03

Wbp11
20
0.124
0.191
−0.517
3.15E−06
1.27E−03

Atf6
20
0.197
0.278
−0.391
3.28E−06
1.32E−03

Jun
20
0.733
0.757
−0.151
3.32E−06
1.33E−03

Tmem230
20
0.117
0.181
−0.463
3.34E−06
1.34E−03

Ccdc117
20
0.21
0.279
−0.326
3.50E−06
1.39E−03

Cggbp1
20
0.171
0.251
−0.432
3.56E−06
1.42E−03

Dock10
20
0.15
0.213
−0.387
3.59E−06
1.43E−03

Manea
20
0.26
0.324
−0.280
3.65E−06
1.45E−03

Rab7
20
0.362
0.457
−0.290
3.80E−06
1.50E−03

Etf1
20
0.261
0.354
−0.384
4.27E−06
1.66E−03

Copz2
20
0.115
0.158
−0.399
4.38E−06
1.70E−03

Rnf10
20
0.282
0.382
−0.376
4.97E−06
1.92E−03

Fdx1l
20
0.115
0.182
−0.441
5.02E−06
1.93E−03

Golt1b
20
0.18
0.259
−0.410
5.07E−06
1.95E−03

Fcrla
20
0.252
0.361
−0.333
5.29E−06
2.02E−03

Plekha2
20
0.216
0.305
−0.386
5.35E−06
2.04E−03

Hbp1
20
0.2
0.271
−0.332
5.38E−06
2.05E−03

Emc2
20
0.167
0.15
0.151
5.56E−06
2.11E−03

Ryr1
20
0.23
0.32
−0.341
5.72E−06
2.17E−03

Al467606
20
0.103
0.164
−0.523
5.77E−06
2.19E−03

Tuba1a
20
0.291
0.41
−0.449
5.90E−06
2.23E−03

Rab5a
20
0.284
0.366
−0.294
6.49E−06
2.43E−03

Nudt9
20
0.179
0.252
−0.386
6.54E−06
2.44E−03

Taz
20
0.138
0.193
−0.366
6.60E−06
2.46E−03

Oser1
20
0.234
0.317
−0.348
6.73E−06
2.51E−03

2300009A05Rik
20
0.129
0.2
−0.421
6.99E−06
2.59E−03

Gigyf2
20
0.109
0.173
−0.503
7.09E−06
2.63E−03

Tmed3
20
0.344
0.437
−0.304
7.37E−06
2.72E−03

Mkrn1
20
0.391
0.477
−0.262
7.63E−06
2.80E−03

Bbs9
20
0.206
0.29
−0.360
7.79E−06
2.86E−03

Ddx24
20
0.193
0.273
−0.385
7.92E−06
2.90E−03

Hint2
20
0.165
0.238
−0.341
8.36E−06
3.04E−03

Tnfaip3
20
0.194
0.27
−0.361
8.39E−06
3.04E−03

Vamp8
20
0.502
0.644
−0.277
8.42E−06
3.05E−03

Gem
20
0.198
0.181
0.200
8.67E−06
3.14E−03

Guk1
20
0.211
0.302
−0.346
8.88E−06
3.20E−03

Slain1
20
0.166
0.233
−0.350
9.30E−06
3.34E−03

Ccnd2
20
0.404
0.526
−0.335
9.66E−06
3.46E−03

Rbm3
20
0.773
0.888
−0.244
9.83E−06
3.50E−03

Arpc1a
20
0.335
0.443
−0.330
9.90E−06
3.52E−03

Fam168b
20
0.111
0.173
−0.481
9.97E−06
3.55E−03

Gosr2
20
0.265
0.368
−0.384
1.02E−05
3.62E−03

Nudc
20
0.235
0.336
−0.392
1.03E−05
3.64E−03

0610012G03Rik
20
0.154
0.231
−0.418
1.04E−05
3.69E−03

Rnf11
20
0.11
0.168
−0.386
1.07E−05
3.79E−03

BC004004
20
0.438
0.576
−0.318
1.08E−05
3.79E−03

Tspan31
20
0.115
0.187
−0.449
1.09E−05
3.85E−03

Qrich1
20
0.167
0.242
−0.407
1.15E−05
4.04E−03

Ccm2
20
0.227
0.323
−0.336
1.15E−05
4.04E−03

Bhlhe41
20
0.247
0.335
−0.419
1.17E−05
4.09E−03

Usf2
20
0.135
0.203
−0.405
1.17E−05
4.10E−03

Chrac1
20
0.207
0.29
−0.380
1.24E−05
4.30E−03

Arpc2
20
0.622
0.781
−0.295
1.28E−05
4.44E−03

Cnot11
20
0.108
0.157
−0.413
1.40E−05
4.80E−03

Gorasp2
20
0.446
0.569
−0.313
1.41E−05
4.83E−03

Kcnq1ot1
20
0.209
0.287
−0.385
1.43E−05
4.88E−03

Srpk2
20
0.203
0.282
−0.378
1.45E−05
4.95E−03

Rfk
20
0.131
0.206
−0.441
1.53E−05
5.18E−03

Rab24
20
0.154
0.234
−0.432
1.54E−05
5.20E−03

Ndufb4
20
0.409
0.522
−0.306
1.61E−05
5.43E−03

Brd2
20
0.296
0.387
−0.323
1.69E−05
5.66E−03

Adssl1
20
0.125
0.196
−0.370
1.74E−05
5.78E−03

Pnrc2
20
0.157
0.237
−0.376
1.77E−05
5.87E−03

Evi2a
20
0.473
0.593
−0.315
1.77E−05
5.88E−03

Gng12
20
0.157
0.228
−0.365
1.84E−05
6.07E−03

Chmp1a
20
0.102
0.159
−0.497
1.84E−05
6.07E−03

Smchd1
20
0.289
0.38
−0.344
1.87E−05
6.16E−03

Ccdc88a
20
0.255
0.337
−0.334
1.99E−05
6.49E−03

Gna13
20
0.152
0.213
−0.430
2.00E−05
6.52E−03

Lyn
20
0.119
0.173
−0.419
2.08E−05
6.77E−03

St8sia4
20
0.25
0.345
−0.376
2.10E−05
6.82E−03

Psmg4
20
0.195
0.275
−0.388
2.13E−05
6.89E−03

Tgoln1
20
0.229
0.324
−0.362
2.15E−05
6.95E−03

Fam46c
20
0.658
0.79
−0.265
2.16E−05
6.98E−03

Eif4g2
20
0.537
0.677
−0.295
2.18E−05
7.03E−03

C130026l21Rik
20
0.151
0.213
−0.399
2.19E−05
7.04E−03

Mat2b
20
0.252
0.344
−0.338
2.20E−05
7.09E−03

Gde1
20
0.181
0.266
−0.387
2.32E−05
7.41E−03

Atp6v1f
20
0.587
0.727
−0.290
2.33E−05
7.45E−03

Tob1
20
0.165
0.231
−0.381
2.37E−05
7.55E−03

Bcl7c
20
0.256
0.34
−0.338
2.44E−05
7.75E−03

B4galnt1
20
0.185
0.258
−0.365
2.44E−05
7.76E−03

Nudcd3
20
0.138
0.186
−0.361
2.45E−05
7.77E−03

Swap70
20
0.121
0.167
−0.377
2.51E−05
7.95E−03

Arf6
20
0.517
0.643
−0.286
2.53E−05
8.00E−03

Dennd5b
20
0.396
0.469
−0.243
2.55E−05
8.06E−03

Ndel1
20
0.116
0.178
−0.469
2.59E−05
8.15E−03

Kras
20
0.142
0.207
−0.440
2.60E−05
8.17E−03

Smim7
20
0.241
0.326
−0.324
2.65E−05
8.31E−03

1810026J23Rik
20
0.094
0.153
−0.443
2.67E−05
8.34E−03

Atp9a
20
0.128
0.19
−0.423
2.71E−05
8.46E−03

Yipf2
20
0.214
0.308
−0.334
2.73E−05
8.53E−03

Ube2j2
20
0.272
0.366
−0.335
2.77E−05
8.63E−03

Trnau1ap
20
0.108
0.161
−0.419
2.87E−05
8.93E−03

Abhd16a
20
0.135
0.206
−0.394
2.90E−05
8.99E−03

Bmyc
20
0.13
0.184
−0.383
3.01E−05
9.31E−03

Denr
20
0.293
0.395
−0.316
3.11E−05
9.57E−03

Rab2a
20
0.595
0.708
−0.259
3.14E−05
9.63E−03

Luc7l3
20
0.14
0.181
−0.363
3.23E−05
9.88E−03

Ncf4
20
0.301
0.395
−0.327
3.26E−05
9.93E−03

Cnbp
20
0.622
0.75
−0.250
3.32E−05
1.01E−02

Snapc5
20
0.15
0.212
−0.393
3.85E−05
1.16E−02

Zfp64
20
0.126
0.193
−0.454
4.04E−05
1.20E−02

Sec24c
20
0.127
0.191
−0.408
4.05E−05
1.21E−02

Zfand2b
20
0.125
0.192
−0.414
4.07E−05
1.21E−02

Fuca1
20
0.293
0.398
−0.328
4.11E−05
1.22E−02

Tmem5
20
0.105
0.162
−0.413
4.23E−05
1.25E−02

Rgs10
20
0.417
0.523
−0.280
4.28E−05
1.26E−02

Vamp2
20
0.182
0.26
−0.367
4.30E−05
1.27E−02

Haus3
20
0.349
0.455
−0.284
4.35E−05
1.28E−02

Sept11
20
0.213
0.285
−0.341
4.47E−05
1.31E−02

Fam204a
20
0.164
0.241
−0.372
4.48E−05
1.31E−02

Tap1
20
0.164
0.221
−0.349
4.49E−05
1.32E−02

Pex2
20
0.167
0.215
−0.335
4.57E−05
1.34E−02

Polr2e
20
0.275
0.34
−0.251
4.64E−05
1.36E−02

Tmem203
20
0.147
0.219
−0.362
4.65E−05
1.36E−02

Grpel1
20
0.3
0.42
−0.326
4.67E−05
1.36E−02

Vps37a
20
0.185
0.267
−0.336
4.70E−05
1.37E−02

Cd164
20
0.27
0.349
−0.328
4.76E−05
1.39E−02

Gtf2a2
20
0.247
0.342
−0.357
4.91E−05
1.42E−02

Cbx4
20
0.163
0.232
−0.356
4.97E−05
1.44E−02

Apitd1
20
0.156
0.202
−0.370
5.12E−05
1.47E−02

Rhobtb1
20
0.195
0.272
−0.377
5.16E−05
1.48E−02

Strap
20
0.251
0.341
−0.364
5.23E−05
1.50E−02

Nek7
20
0.39
0.514
−0.308
5.40E−05
1.54E−02

Egln2
20
0.204
0.288
−0.323
5.50E−05
1.57E−02

Atp6v0d1
20
0.325
0.385
−0.232
5.66E−05
1.61E−02

Htatsf1
20
0.104
0.167
−0.451
5.68E−05
1.62E−02

Csde1
20
0.311
0.399
−0.301
5.73E−05
1.63E−02

Pdcd4
20
0.301
0.391
−0.267
5.87E−05
1.66E−02

Cd82
20
0.192
0.234
−0.256
5.97E−05
1.69E−02

Man1a2
20
0.156
0.224
−0.386
6.04E−05
1.70E−02

Pafah1b1
20
0.292
0.374
−0.313
6.33E−05
1.77E−02

Slc48a1
20
0.254
0.346
−0.314
6.68E−05
1.85E−02

Kmt2e
20
0.362
0.469
−0.310
6.82E−05
1.89E−02

Irf2
20
0.253
0.34
−0.329
7.14E−05
1.96E−02

Atp6v0b
20
0.48
0.589
−0.242
7.17E−05
1.96E−02

Yipf4
20
0.287
0.373
−0.292
7.27E−05
1.99E−02

Atg3
20
0.271
0.37
−0.332
7.36E−05
2.01E−02

Arl8b
20
0.148
0.211
−0.400
7.57E−05
2.06E−02

Prr5
20
0.442
0.567
−0.303
7.64E−05
2.08E−02

Vapb
20
0.167
0.245
−0.396
7.81E−05
2.12E−02

Eif4enif1
20
0.13
0.183
−0.382
7.98E−05
2.16E−02

Ctnnbl1
20
0.142
0.207
−0.435
8.02E−05
2.17E−02

Bola3
20
0.24
0.339
−0.343
8.07E−05
2.18E−02

Ddx3x
20
0.237
0.325
−0.318
8.09E−05
2.18E−02

Insig1
20
0.239
0.322
−0.339
8.14E−05
2.19E−02

Map3k1
20
0.124
0.166
−0.341
8.16E−05
2.20E−02

H2-Q7
20
0.095
0.153
−0.452
8.22E−05
2.21E−02

Uvrag
20
0.127
0.193
−0.435
8.30E−05
2.22E−02

Abcb1b
20
0.096
0.154
−0.442
8.55E−05
2.28E−02

Phf3
20
0.176
0.218
−0.261
8.77E−05
2.33E−02

Fubp1
20
0.107
0.168
−0.459
8.96E−05
2.38E−02

Eps15
20
0.111
0.166
−0.412
9.03E−05
2.39E−02

4833439L19Rik
20
0.116
0.153
−0.324
9.16E−05
2.42E−02

Gpr180
20
0.153
0.202
−0.308
9.17E−05
2.42E−02

Cops7a
20
0.178
0.261
−0.380
9.26E−05
2.44E−02

Lrrc59
20
0.494
0.645
−0.306
9.48E−05
2.49E−02

Nus1
20
0.207
0.264
−0.326
9.65E−05
2.52E−02

Chuk
20
0.119
0.153
−0.352
9.71E−05
2.54E−02

Maf1
20
0.234
0.292
−0.270
9.92E−05
2.58E−02

Cnot7
20
0.185
0.249
−0.335
1.01E−04
2.63E−02

Smim10l1
20
0.116
0.175
−0.408
1.02E−04
2.66E−02

Babam1
20
0.302
0.392
−0.301
1.03E−04
2.67E−02

Arfgap1
20
0.126
0.181
−0.404
1.14E−04
2.92E−02

Eif4g3
20
0.144
0.176
−0.277
1.16E−04
2.96E−02

DynIl2
20
0.193
0.272
−0.357
1.19E−04
3.04E−02

Coq2
20
0.094
0.151
−0.449
1.22E−04
3.09E−02

Pla2g12a
20
0.233
0.328
−0.338
1.24E−04
3.14E−02

Atg13
20
0.11
0.159
−0.366
1.26E−04
3.19E−02

Abhd17b
20
0.128
0.192
−0.439
1.26E−04
3.19E−02

Raf1
20
0.234
0.324
−0.364
1.29E−04
3.25E−02

Ppp1r14b
20
0.175
0.253
−0.391
1.30E−04
3.27E−02

Chtop
20
0.236
0.301
−0.292
1.33E−04
3.32E−02

Ccdc127
20
0.164
0.207
−0.273
1.39E−04
3.45E−02

Papola
20
0.368
0.453
−0.276
1.40E−04
3.46E−02

St3gal6
20
0.168
0.223
−0.332
1.42E−04
3.50E−02

Bloc1s2
20
0.142
0.202
−0.417
1.45E−04
3.55E−02

Ndnl2
20
0.125
0.175
−0.381
1.46E−04
3.58E−02

Ccnt2
20
0.174
0.227
−0.331
1.46E−04
3.58E−02

Map2k3
20
0.134
0.181
−0.363
1.49E−04
3.64E−02

Morf4l1
20
0.559
0.68
−0.265
1.55E−04
3.76E−02

Dcaf11
20
0.185
0.255
−0.353
1.69E−04
4.05E−02

Mrfap1
20
0.598
0.725
−0.260
1.69E−04
4.06E−02

Klhdc2
20
0.442
0.563
−0.295
1.71E−04
4.09E−02

Slc25a51
20
0.143
0.196
−0.368
1.72E−04
4.11E−02

Papd4
20
0.149
0.208
−0.336
1.72E−04
4.11E−02

Brap
20
0.121
0.168
−0.372
1.74E−04
4.15E−02

Shc1
20
0.108
0.158
−0.425
1.76E−04
4.18E−02

Mcfd2
20
0.126
0.187
−0.385
1.77E−04
4.22E−02

Csnk1g3
20
0.276
0.336
−0.228
1.80E−04
4.26E−02

Dpm1
20
0.153
0.196
−0.276
1.88E−04
4.44E−02

Srsf5
20
0.493
0.609
−0.277
1.90E−04
4.47E−02

Gps2
20
0.146
0.215
−0.423
1.91E−04
4.48E−02

Rnf167
20
0.154
0.211
−0.344
1.91E−04
4.49E−02

1700017B05Rik
20
0.273
0.353
−0.296
1.91E−04
4.50E−02

Letm1
20
0.182
0.247
−0.355
1.93E−04
4.52E−02

Rnf187
20
0.378
0.468
−0.260
1.94E−04
4.54E−02

Rnf114
20
0.143
0.18
−0.283
1.95E−04
4.56E−02

Eif3a
20
0.314
0.424
−0.332
1.95E−04
4.56E−02

Rusc1
20
0.244
0.331
−0.315
1.96E−04
4.58E−02

Armc1
20
0.135
0.186
−0.366
2.04E−04
4.75E−02

Gpr65
20
0.151
0.213
−0.348
2.07E−04
4.81E−02

Ubxn4
20
0.547
0.666
−0.275
2.12E−04
4.91E−02

Zfp622
20
0.126
0.17
−0.349
2.16E−04
4.98E−02

Rnf4
20
0.206
0.26
−0.314
2.16E−04
4.99E−02

Ighg1
21
0.256
0.029
1.795
5.93E−33
3.67E−29

Mcpt2
21
0.202
0
5.176
1.61E−26
6.87E−23

Nr4a2
21
0.546
0.834
−0.933
1.44E−22
4.38E−19

Ppia
21
1
0.997
0.329
1.64E−18
3.62E−15

Slc25a20
21
0.511
0.784
−0.865
6.90E−18
1.44E−14

Nfkbia
21
0.763
0.443
0.993
5.20E−17
9.89E−14

Hspa1a
21
0.385
0.135
1.750
6.60E−17
1.23E−13

Mcpt1
21
0.205
0.021
4.061
1.16E−16
2.11E−13

Tm2d2
21
0.621
0.815
−0.625
2.38E−16
4.24E−13

Jun
21
0.609
0.443
0.934
1.06E−15
1.79E−12

Iglc1
21
0.464
0.768
−0.583
1.17E−15
1.95E−12

Zfand5
21
0.498
0.739
−0.854
9.22E−15
1.42E−11

Btg2
21
0.962
0.974
−0.460
1.10E−14
1.68E−11

Irf7
21
0.196
0.456
−1.092
2.13E−13
2.81E−10

Ckb
21
0.934
0.905
0.434
4.26E−13
5.42E−10

Ifi30
21
0.842
0.697
0.508
4.52E−13
5.72E−10

Ly6e
21
0.435
0.662
−0.839
5.27E−13
6.60E−10

Ifi27l2a
21
0.353
0.609
−1.014
9.74E−13
1.20E−09

Gapdh
21
0.987
0.963
0.249
3.00E−12
3.48E−09

Tnfaip2
21
0.177
0.43
−1.252
3.03E−12
3.50E−09

Tuba1b
21
0.741
0.573
0.851
2.00E−11
2.10E−08

Igkv1-135
21
0.123
0.396
−1.236
6.93E−11
6.87E−08

Rgs2
21
0.741
0.879
−0.603
6.94E−11
6.87E−08

Neat1
21
0.735
0.594
0.579
2.12E−10
1.95E−07

Atp5b
21
0.95
0.923
0.322
3.56E−10
3.15E−07

Il1r2
21
0.174
0.435
−0.959
3.81E−10
3.34E−07

Hfe
21
0.461
0.261
0.857
5.83E−10
5.00E−07

Calr
21
0.937
0.847
0.254
9.89E−10
8.22E−07

Slc25a5
21
0.978
0.96
0.323
1.47E−09
1.17E−06

Tmem50b
21
0.388
0.607
−0.594
1.86E−09
1.47E−06

B930036N10Rik
21
0.167
0.026
1.176
2.12E−09
1.65E−06

Coro1a
21
0.987
0.976
0.200
2.53E−09
1.94E−06

Lpar6
21
0.315
0.517
−0.790
3.20E−09
2.38E−06

Vps37b
21
0.164
0.393
−1.167
3.62E−09
2.68E−06

Man2b1
21
0.82
0.744
0.355
3.71E−09
2.72E−06

Rheb
21
0.852
0.918
−0.319
4.00E−09
2.93E−06

Tifab
21
0.7
0.813
−0.378
5.43E−09
3.89E−06

Errfi1
21
0.246
0.454
−0.863
7.19E−09
5.06E−06

Ctla2b
21
0.473
0.639
−0.685
8.48E−09
5.90E−06

Rpn2
21
0.653
0.546
0.477
8.74E−09
6.05E−06

Zfp36
21
0.918
0.916
0.470
1.29E−08
8.73E−06

Junb
21
0.978
0.984
−0.242
2.25E−08
1.46E−05

Ildr1
21
0.11
0.311
−1.204
3.02E−08
1.91E−05

Hspa1b
21
0.17
0.053
1.234
7.86E−08
4.55E−05

Bcl2a1d
21
0.886
0.852
0.372
1.59E−07
8.79E−05

Dck
21
0.237
0.443
−0.663
1.81E−07
9.86E−05

Hsp90aa1
21
0.773
0.681
0.462
2.22E−07
1.19E−04

Nr4a1
21
0.811
0.931
−0.351
2.63E−07
1.39E−04

Apol10b
21
0.066
0.214
−0.935
3.25E−07
1.68E−04

Igkc
21
1
1
0.404
3.60E−07
1.84E−04

Fndc5
21
0.322
0.515
−0.592
3.83E−07
1.96E−04

Ndel1
21
0.438
0.612
−0.617
4.54E−07
2.28E−04

Cct8
21
0.785
0.707
0.364
6.91E−07
3.33E−04

Herpud1
21
0.754
0.868
−0.354
7.11E−07
3.42E−04

Arl4a
21
0.303
0.451
−0.646
7.64E−07
3.64E−04

Grasp
21
0.375
0.57
−0.773
8.38E−07
3.95E−04

Cdc42
21
0.978
0.963
0.232
9.98E−07
4.64E−04

Txnip
21
0.139
0.319
−0.939
1.07E−06
4.96E−04

Tmem243
21
0.451
0.599
−0.412
1.20E−06
5.45E−04

Isg15
21
0.11
0.277
−0.924
1.30E−06
5.86E−04

Ptger4
21
0.3
0.158
0.743
1.50E−06
6.65E−04

Rap2a
21
0.429
0.245
0.789
1.51E−06
6.68E−04

Runx3
21
0.42
0.565
−0.524
1.60E−06
7.07E−04

Itgb7
21
0.735
0.649
0.391
1.90E−06
8.21E−04

Ifngr2
21
0.536
0.683
−0.382
2.01E−06
8.59E−04

Atf4
21
0.59
0.802
−0.561
2.12E−06
9.02E−04

Arl4c
21
0.183
0.348
−0.993
2.50E−06
1.04E−03

Ddost
21
0.738
0.673
0.309
2.98E−06
1.21E−03

Eef1d
21
0.886
0.852
0.198
3.02E−06
1.22E−03

Ifi44l
21
0.17
0.306
−0.572
3.44E−06
1.38E−03

Pcyt2
21
0.344
0.462
−0.494
3.49E−06
1.39E−03

Lztfl1
21
0.281
0.195
0.710
3.72E−06
1.47E−03

Lbh
21
0.517
0.628
−0.370
4.19E−06
1.63E−03

Ap1s3
21
0.691
0.773
−0.306
4.33E−06
1.69E−03

Ifitm3
21
0.905
0.963
−0.236
5.02E−06
1.93E−03

Iglc3
21
0.069
0.224
−0.825
5.42E−06
2.06E−03

Ifrd1
21
0.483
0.678
−0.603
6.82E−06
2.54E−03

Hnrnpa2b1
21
0.931
0.91
0.297
7.39E−06
2.72E−03

Ppp1r2
21
0.571
0.734
−0.428
7.98E−06
2.91E−03

Pkm
21
0.839
0.826
0.302
8.35E−06
3.03E−03

Tagln2
21
0.95
0.918
0.288
9.33E−06
3.34E−03

Hnrnpa3
21
0.905
0.868
0.301
1.00E−05
3.57E−03

Sgk1
21
0.268
0.438
−0.750
1.01E−05
3.57E−03

Ldha
21
0.962
0.931
0.319
1.14E−05
3.98E−03

Irf8
21
0.924
0.955
−0.160
1.19E−05
4.15E−03

Kdm6b
21
0.691
0.58
0.457
1.21E−05
4.21E−03

Adgre5
21
0.568
0.475
0.397
1.29E−05
4.46E−03

Ubb
21
1
0.979
0.253
1.46E−05
4.98E−03

Eno1
21
0.751
0.583
0.517
1.77E−05
5.88E−03

S100a13
21
0.722
0.588
0.304
1.82E−05
6.02E−03

A530040E14Rik
21
0.095
0.235
−0.947
1.89E−05
6.21E−03

Spg21
21
0.767
0.86
−0.312
1.94E−05
6.35E−03

Gna13
21
0.584
0.704
−0.487
2.08E−05
6.78E−03

Sla
21
0.773
0.654
0.364
2.12E−05
6.87E−03

Gns
21
0.363
0.515
−0.504
2.16E−05
6.97E−03

Vmp1
21
0.618
0.443
0.491
2.18E−05
7.04E−03

Amica1
21
0.634
0.789
−0.272
2.40E−05
7.64E−03

Snrpd1
21
0.694
0.652
0.267
2.47E−05
7.82E−03

Adrb2
21
0.36
0.206
0.769
2.62E−05
8.21E−03

Pdia6
21
0.767
0.644
0.410
2.75E−05
8.56E−03

Eif4a1
21
0.978
0.966
0.271
3.00E−05
9.28E−03

Ifi44
21
0.054
0.161
−1.018
3.09E−05
9.50E−03

Ppib
21
0.946
0.931
0.171
3.61E−05
1.09E−02

Arih2
21
0.372
0.562
−0.629
3.75E−05
1.13E−02

Fam162a
21
0.486
0.351
0.345
3.96E−05
1.18E−02

Srsf5
21
0.845
0.873
−0.330
4.04E−05
1.20E−02

2200002D01Rik
21
0.142
0.269
−0.786
4.76E−05
1.39E−02

Tkt
21
0.748
0.673
0.338
4.92E−05
1.42E−02

Pa2g4
21
0.621
0.501
0.389
5.14E−05
1.48E−02

Ezr
21
0.521
0.391
0.319
5.23E−05
1.50E−02

Fxyd5
21
0.754
0.633
0.274
5.42E−05
1.55E−02

Il1b
21
0.476
0.594
−0.609
5.42E−05
1.55E−02

Prkar2a
21
0.546
0.699
−0.435
5.51E−05
1.57E−02

Fbl
21
0.836
0.786
0.303
5.53E−05
1.58E−02

Stt3b
21
0.473
0.559
−0.435
5.57E−05
1.59E−02

Actb
21
1
1
0.363
5.76E−05
1.63E−02

Dusp1
21
0.861
0.768
0.517
6.02E−05
1.70E−02

Fam174a
21
0.565
0.71
−0.382
6.07E−05
1.71E−02

Tiparp
21
0.107
0.245
−0.919
6.14E−05
1.72E−02

Zfp706
21
0.877
0.881
−0.202
6.26E−05
1.75E−02

Baz1a
21
0.555
0.501
0.343
6.50E−05
1.81E−02

Hnrnpu
21
0.688
0.588
0.377
6.67E−05
1.85E−02

Eif3l
21
0.666
0.578
0.303
6.88E−05
1.90E−02

Got2
21
0.59
0.472
0.430
7.08E−05
1.95E−02

Hlx
21
0.136
0.285
−0.749
7.12E−05
1.96E−02

Magohb
21
0.199
0.348
−0.617
7.14E−05
1.96E−02

Dgat1
21
0.088
0.214
−1.018
7.42E−05
2.03E−02

Cdv3
21
0.555
0.654
−0.426
7.53E−05
2.06E−02

Litaf
21
0.694
0.799
−0.273
7.86E−05
2.13E−02

Igkv12-44
21
0.174
0.077
0.985
8.44E−05
2.26E−02

Napsa
21
0.767
0.665
0.374
8.62E−05
2.30E−02

Evi2a
21
0.612
0.755
−0.246
9.30E−05
2.45E−02

Dusp2
21
0.407
0.264
0.608
9.44E−05
2.48E−02

AC125149.3
21
0.088
0.219
−0.978
9.63E−05
2.52E−02

Orai1
21
0.596
0.446
0.338
1.10E−04
2.83E−02

Agpat4
21
0.511
0.673
−0.476
1.10E−04
2.84E−02

Mt1
21
0.486
0.319
0.475
1.11E−04
2.84E−02

Ube2l6
21
0.211
0.332
−0.593
1.13E−04
2.88E−02

Fndc3a
21
0.098
0.232
−0.888
1.14E−04
2.91E−02

Gm
21
0.839
0.776
0.296
1.28E−04
3.22E−02

Fh1
21
0.552
0.417
0.471
1.35E−04
3.37E−02

Commd8
21
0.804
0.852
−0.222
1.38E−04
3.42E−02

Snrnp70
21
0.517
0.406
0.365
1.42E−04
3.51E−02

Dapk2
21
0.435
0.559
−0.381
1.43E−04
3.53E−02

Brox
21
0.132
0.259
−0.540
1.49E−04
3.64E−02

Mnda
21
0.65
0.541
0.528
1.54E−04
3.74E−02

Btg1
21
0.965
0.987
−0.253
1.56E−04
3.77E−02

Mcm7
21
0.218
0.098
0.815
1.63E−04
3.93E−02

Map1lc3a
21
0.183
0.33
−0.666
1.69E−04
4.06E−02

Ubald2
21
0.606
0.739
−0.445
1.75E−04
4.17E−02

Ptp4a1
21
0.539
0.665
−0.401
1.77E−04
4.21E−02

Prr13
21
0.817
0.881
−0.200
1.80E−04
4.26E−02

Atxn7l3b
21
0.514
0.649
−0.356
1.84E−04
4.35E−02

Nlrp3
21
0.107
0.219
−0.852
1.84E−04
4.35E−02

Nabp1
21
0.249
0.417
−0.602
1.87E−04
4.41E−02

Gngt2
21
0.338
0.478
−0.369
1.93E−04
4.52E−02

Chic2
21
0.647
0.768
−0.314
1.94E−04
4.55E−02

Tspan13
21
0.808
0.889
−0.216
2.01E−04
4.68E−02

Al467606
21
0.189
0.084
0.798
2.03E−04
4.71E−02

Actg1
22
0.977
0.98
0.479
3.28E−21
9.09E−18

Vim
22
0.663
0.42
0.827
1.03E−20
2.79E−17

Ccl7
22
0.286
0.037
3.742
3.69E−19
8.76E−16

Ighg1
22
0.166
0.007
3.332
4.61E−19
1.08E−15

AW112010
22
0.288
0.573
−1.156
6.67E−19
1.52E−15

Tspan13
22
0.505
0.732
−0.833
4.47E−18
9.47E−15

HP
22
0.301
0.075
1.775
2.69E−17
5.24E−14

Ccl2
22
0.416
0.139
1.980
9.74E−16
1.65E−12

Fth1
22
0.995
1
−0.457
3.57E−15
5.74E−12

Ccl9
22
0.635
0.41
0.687
1.56E−14
2.34E−11

Apol7c
22
0.089
0.247
−1.747
2.61E−14
3.85E−11

Aif1
22
0.663
0.858
−0.513
3.02E−14
4.38E−11

Hspa8
22
0.936
0.878
0.333
4.03E−14
5.76E−11

Dnase1l3
22
0.171
0.366
−1.262
1.12E−13
1.50E−10

Cebpb
22
0.977
0.905
0.489
4.18E−13
5.33E−10

Dusp1
22
0.939
0.898
0.547
5.81E−13
7.26E−10

Tm2d2
22
0.304
0.441
−0.730
1.09E−12
1.34E−09

Irf7
22
0.24
0.471
−1.077
1.15E−12
1.40E−09

Mgst1
22
0.311
0.122
1.436
2.83E−12
3.31E−09

Isg15
22
0.26
0.485
−1.002
3.09E−12
3.57E−09

Cxcl2
22
0.781
0.549
0.778
4.23E−12
4.81E−09

Cd74
22
0.857
0.966
−0.387
7.80E−12
8.58E−09

Ftl1
22
1
1
−0.297
2.50E−11
2.61E−08

Irf8
22
0.393
0.583
−0.747
3.02E−11
3.11E−08

Chil3
22
0.153
0.02
2.589
3.95E−11
4.03E−08

Lpar6
22
0.23
0.444
−0.964
4.51E−11
4.56E−08

Cxcl16
22
0.454
0.644
−0.679
7.38E−11
7.28E−08

Asb2
22
0.112
0.302
−1.341
7.54E−11
7.41E−08

Napsa
22
0.385
0.254
0.886
7.66E−11
7.50E−08

Ccl6
22
0.806
0.631
0.287
1.11E−10
1.07E−07

Tgfb1
22
0.712
0.841
−0.483
1.41E−10
1.34E−07

Fn1
22
0.255
0.102
1.534
3.10E−10
2.79E−07

H2-DMb1
22
0.607
0.79
−0.499
3.44E−10
3.06E−07

S100a4
22
0.411
0.214
0.571
3.58E−10
3.17E−07

Aldh2
22
0.464
0.336
0.668
3.60E−10
3.18E−07

Arid5a
22
0.158
0.356
−1.089
3.65E−10
3.21E−07

Malat1
22
1
1
−0.442
5.65E−10
4.86E−07

Tmsb4x
22
1
1
−0.261
6.35E−10
5.40E−07

S100a6
22
0.548
0.437
0.632
9.21E−10
7.70E−07

Batf
22
0.105
0.305
−1.283
1.29E−09
1.04E−06

Adamdec1
22
0.163
0.312
−1.284
1.48E−09
1.18E−06

Igkv1-135
22
0.02
0.163
−1.953
1.89E−09
1.48E−06

Rnf149
22
0.589
0.783
−0.517
2.35E−09
1.82E−06

H2-Aa
22
0.763
0.932
−0.214
2.40E−09
1.85E−06

Alox5ap
22
0.548
0.4
0.711
2.80E−09
2.13E−06

Gbp7
22
0.097
0.278
−1.220
2.81E−09
2.13E−06

Vps37b
22
0.148
0.315
−1.322
2.94E−09
2.22E−06

F13a1
22
0.214
0.068
1.352
2.98E−09
2.24E−06

Emp3
22
0.518
0.346
0.588
3.67E−09
2.70E−06

Iglc1
22
0.27
0.481
−0.819
4.60E−09
3.33E−06

Egr2
22
0.276
0.105
1.235
8.97E−09
6.19E−06

Lair1
22
0.276
0.495
−0.673
1.02E−08
6.97E−06

Hjurp
22
0.071
0.217
−1.397
1.05E−08
7.13E−06

Egr1
22
0.592
0.366
0.285
1.12E−08
7.61E−06

Atp6v0e
22
0.64
0.763
−0.402
1.74E−08
1.15E−05

Irf1
22
0.105
0.278
−1.311
2.32E−08
1.50E−05

S100a10
22
0.413
0.258
0.723
2.42E−08
1.56E−05

Tapbp
22
0.36
0.532
−0.598
2.57E−08
1.65E−05

Neurl3
22
0.319
0.505
−0.681
2.64E−08
1.69E−05

Pla2g2d
22
0.059
0.186
−1.637
2.71E−08
1.73E−05

Acp5
22
0.298
0.444
−0.863
3.31E−08
2.07E−05

Fgl2
22
0.194
0.373
−0.766
3.42E−08
2.14E−05

C3
22
0.235
0.095
1.228
3.80E−08
2.35E−05

Mxd1
22
0.133
0.292
−0.960
5.12E−08
3.07E−05

Naca
22
0.86
0.756
0.200
5.85E−08
3.47E−05

Pf4
22
0.344
0.268
1.093
6.03E−08
3.57E−05

H2-DMb2
22
0.434
0.62
−0.540
6.59E−08
3.88E−05

Ctsz
22
0.821
0.854
−0.372
7.46E−08
4.34E−05

Batf3
22
0.276
0.464
−0.688
7.85E−08
4.55E−05

Ppp1r15a
22
0.446
0.542
−0.637
9.41E−08
5.37E−05

Coro1a
22
0.844
0.776
0.338
9.49E−08
5.41E−05

Anxa1
22
0.286
0.159
1.069
1.07E−07
6.04E−05

Svbp
22
0.179
0.346
−0.827
1.14E−07
6.44E−05

Btg1
22
0.916
0.959
−0.344
1.25E−07
7.03E−05

Hpgds
22
0.105
0.251
−0.982
1.41E−07
7.87E−05

Gda
22
0.258
0.105
1.080
1.49E−07
8.26E−05

Srgn
22
0.895
0.81
0.343
1.66E−07
9.13E−05

Ptgs1
22
0.23
0.373
−0.825
1.67E−07
9.14E−05

Anxa2
22
0.418
0.312
0.668
2.08E−07
1.12E−04

Cd37
22
0.184
0.064
1.128
2.27E−07
1.21E−04

Rnasel
22
0.097
0.258
−1.028
2.29E−07
1.22E−04

Socs3
22
0.258
0.4
−0.880
2.56E−07
1.35E−04

Grb2
22
0.383
0.553
−0.530
2.69E−07
1.41E−04

AB124611
22
0.342
0.197
0.557
2.88E−07
1.51E−04

H2-Eb1
22
0.719
0.875
−0.162
3.43E−07
1.76E−04

Herpud1
22
0.281
0.427
−0.720
3.65E−07
1.87E−04

Marcks
22
0.571
0.759
−0.384
4.35E−07
2.20E−04

Plin2
22
0.679
0.515
0.440
4.85E−07
2.42E−04

Ahnak
22
0.37
0.21
0.634
5.19E−07
2.58E−04

Fxyd5
22
0.651
0.559
0.399
6.21E−07
3.03E−04

P2ry14
22
0.064
0.186
−1.294
6.30E−07
3.07E−04

Hbegf
22
0.179
0.047
1.831
6.69E−07
3.23E−04

Srsf5
22
0.64
0.664
−0.284
6.84E−07
3.30E−04

C130050O18Rik
22
0.171
0.264
−0.678
8.69E−07
4.08 E−04

Ier3
22
0.523
0.339
0.543
9.39E−07
4.39E−04

Slco3a1
22
0.048
0.166
−1.361
1.00E−06
4.66E−04

Lgals3bp
22
0.171
0.339
−0.835
1.10E−06
5.06E−04

Csf1r
22
0.727
0.776
−0.486
1.14E−06
5.25E−04

S100a11
22
0.543
0.434
0.494
1.18E−06
5.37E−04

Cfp
22
0.556
0.38
0.344
1.23E−06
5.60E−04

Klrk1
22
0.059
0.186
−1.286
1.31E−06
5.91E−04

Gbp2b
22
0.107
0.241
−0.981
1.35E−06
6.05E−04

Nr4a1
22
0.666
0.492
0.369
1.40E−06
6.26E−04

Prdm1
22
0.189
0.373
−0.693
1.47E−06
6.54E−04

Fam46c
22
0.061
0.197
−1.150
1.61E−06
7.10E−04

Rcan1
22
0.168
0.044
1.957
1.71E−06
7.50E−04

Hspa1a
22
0.214
0.095
0.524
1.73E−06
7.56E−04

Cdk2ap2
22
0.561
0.695
−0.473
1.80E−06
7.85E−04

Clec10a
22
0.227
0.098
1.028
1.93E−06
8.32E−04

Fam46a
22
0.207
0.383
−0.803
1.95E−06
8.37E−04

Cdc42se2
22
0.194
0.353
−0.800
1.95E−06
8.37E−04

Ifnar1
22
0.227
0.329
−0.654
2.13E−06
9.07E−04

Cd44
22
0.625
0.464
0.421
2.16E−06
9.16E−04

Pltp
22
0.375
0.227
0.817
2.21E−06
9.35E−04

Npm1
22
0.781
0.668
0.231
2.33E−06
9.84E−04

Map3k8
22
0.082
0.217
−1.011
2.36E−06
9.96E−04

Runx3
22
0.332
0.441
−0.480
2.40E−06
1.01E−03

Ntpcr
22
0.173
0.298
−0.826
2.45E−06
1.03E−03

Peli1
22
0.207
0.366
−0.754
2.49E−06
1.04E−03

Rbm7
22
0.357
0.536
−0.576
2.52E−06
1.05E−03

Psme2
22
0.523
0.624
−0.403
2.56E−06
1.06E−03

Hn1
22
0.485
0.614
−0.424
2.76E−06
1.14E−03

Msrb1
22
0.569
0.478
0.573
2.83E−06
1.16E−03

Mgat4a
22
0.102
0.227
−0.897
3.15E−06
1.27E−03

Cd14
22
0.801
0.668
0.328
3.26E−06
1.31E−03

Osm
22
0.385
0.234
1.039
3.30E−06
1.32E−03

Rgs2
22
0.518
0.705
−0.605
3.56E−06
1.42E−03

Pgd
22
0.288
0.156
0.747
3.87E−06
1.52E−03

Zfp263
22
0.219
0.353
−0.601
4.01E−06
1.57E−03

Bst2
22
0.421
0.502
−0.428
4.37E−06
1.70E−03

Tcirg1
22
0.253
0.153
0.290
4.44E−06
1.72E−03

Lbh
22
0.27
0.407
−0.695
5.04E−06
1.94E−03

Fam26f
22
0.094
0.22
−1.012
5.94E−06
2.24E−03

Etv3
22
0.191
0.353
−0.678
6.06E−06
2.28E−03

Fosb
22
0.385
0.461
−0.614
6.07E−06
2.29E−03

B2m
22
0.98
0.963
−0.230
6.16E−06
2.32E−03

Actb
22
0.992
1
0.400
6.22E−06
2.34E−03

Calm1
22
0.791
0.831
−0.340
6.37E−06
2.39E−03

Nfkbie
22
0.117
0.254
−0.800
6.52E−06
2.44E−03

Fyb
22
0.492
0.614
−0.489
6.64E−06
2.47E−03

Hic1
22
0.077
0.19
−1.211
7.07E−06
2.62E−03

Abi3
22
0.145
0.281
−0.957
7.26E−06
2.68E−03

Tgfbr1
22
0.151
0.305
−0.751
7.42E−06
2.73E−03

Il6st
22
0.092
0.22
−0.914
7.63E−06
2.80E−03

Ly6c1
22
0.296
0.169
0.222
7.93E−06
2.90E−03

Cd83
22
0.717
0.834
−0.322
7.96E−06
2.91E−03

Slc25a5
22
0.742
0.675
0.258
8.41E−06
3.05E−03

Tm6sf1
22
0.477
0.322
0.432
8.82E−06
3.18E−03

Ybx1
22
0.788
0.817
−0.292
9.72E−06
3.47E−03

Abr
22
0.117
0.247
−0.901
1.06E−05
3.76E−03

Gbp4
22
0.071
0.18
−1.162
1.13E−05
3.96E−03

Btg2
22
0.849
0.912
−0.402
1.34E−05
4.60E−03

AF251705
22
0.533
0.637
−0.460
1.35E−05
4.66E−03

Eif3f
22
0.816
0.759
0.238
1.36E−05
4.67E−03

Clta
22
0.773
0.692
0.232
1.46E−05
4.95E−03

Emp1
22
0.281
0.169
0.835
1.52E−05
5.16E−03

Ifitm6
22
0.418
0.278
0.474
1.57E−05
5.31E−03

Pole4
22
0.196
0.363
−0.595
1.60E−05
5.40E−03

Gm2a
22
0.788
0.875
−0.337
1.66E−05
5.56E−03

Cd81
22
0.398
0.58
−0.407
1.69E−05
5.65E−03

Clec2d
22
0.13
0.285
−0.693
1.70E−05
5.68E−03

H2-K1
22
0.821
0.902
−0.266
1.78E−05
5.89E−03

Eif3e
22
0.605
0.485
0.375
1.82E−05
6.02E−03

Arhgap17
22
0.176
0.292
−0.753
1.87E−05
6.16E−03

S100a13
22
0.449
0.325
0.495
2.10E−05
6.82E−03

Jun
22
0.64
0.498
0.332
2.12E−05
6.87E−03

Tnfaip3
22
0.283
0.39
−0.612
2.13E−05
6.90E−03

Dnajb6
22
0.347
0.451
−0.468
2.16E−05
6.97E−03

Mtpn
22
0.388
0.485
−0.430
2.19E−05
7.06E−03

Srrm2
22
0.436
0.515
−0.404
2.21E−05
7.09E−03

Dab2
22
0.311
0.183
0.890
2.39E−05
7.60E−03

BC005537
22
0.564
0.424
0.457
2.51E−05
7.95E−03

Bcl2l11
22
0.151
0.288
−0.756
2.59E−05
8.14E−03

Slpi
22
0.224
0.122
0.469
2.65E−05
8.31E−03

Pbxip1
22
0.209
0.292
−0.553
2.66E−05
8.33E−03

Ccl3
22
0.622
0.454
0.647
2.69E−05
8.40E−03

Btf3
22
0.768
0.729
0.190
2.71E−05
8.46E−03

Metrnl
22
0.561
0.441
0.405
2.80E−05
8.71E−03

Ifi27l2a
22
0.811
0.841
−0.439
2.91E−05
9.02E−03

Lyz2
22
0.995
0.983
0.273
2.96E−05
9.15E−03

Litaf
22
0.62
0.692
−0.289
3.07E−05
9.44E−03

Icam1
22
0.179
0.312
−0.751
3.19E−05
9.78E−03

Hopx
22
0.25
0.149
0.893
3.34E−05
1.02E−02

Cd86
22
0.388
0.376
−0.227
3.37E−05
1.02E−02

Cx3cr1
22
0.327
0.407
−0.597
3.43E−05
1.04E−02

Cox4i1
22
0.918
0.858
0.173
3.55E−05
1.08E−02

C5ar1
22
0.393
0.241
0.701
3.68E−05
1.11E−02

PISD
22
0.173
0.251
−0.584
3.68E−05
1.11E−02

Ythdc1
22
0.151
0.285
−0.753
3.68E−05
1.11E−02

Rcbtb2
22
0.219
0.376
−0.737
3.90E−05
1.17E−02

Il17ra
22
0.237
0.125
0.712
4.07E−05
1.21E−02

Ocstamp
22
0.051
0.153
−1.131
4.14E−05
1.23E−02

Dusp5
22
0.298
0.403
−0.519
4.48E−05
1.31E−02

Asph
22
0.194
0.302
−0.601
4.64E−05
1.36E−02

Pkm
22
0.597
0.512
0.363
4.83E−05
1.40E−02

Sdc4
22
0.362
0.254
0.962
4.87E−05
1.41E−02

Csnk1e
22
0.135
0.251
−0.720
4.94E−05
1.43E−02

Tmem37
22
0.11
0.231
−0.914
4.94E−05
1.43E−02

Ndufa1
22
0.462
0.492
−0.251
5.07E−05
1.46E−02

P2ry6
22
0.321
0.468
−0.500
5.10E−05
1.47E−02

Idh3b
22
0.242
0.163
0.312
5.74E−05
1.63E−02

Oser1
22
0.401
0.536
−0.408
5.83E−05
1.65E−02

Ptms
22
0.459
0.553
−0.371
5.98E−05
1.69E−02

Mpeg1
22
0.778
0.871
−0.225
6.14E−05
1.72E−02

Ciita
22
0.056
0.156
−1.102
6.16E−05
1.73E−02

Bri3
22
0.597
0.698
−0.331
6.19E−05
1.73E−02

Ighm
22
0.347
0.505
−0.561
6.40E−05
1.79E−02

Ccl24
22
0.63
0.576
0.745
6.83E−05
1.89E−02

Npl
22
0.066
0.153
−1.103
7.04E−05
1.94E−02

P2rx4
22
0.309
0.403
−0.462
7.13E−05
1.96E−02

Ubl3
22
0.559
0.627
−0.295
7.66E−05
2.09E−02

Adam19
22
0.128
0.264
−0.609
8.38E−05
2.24E−02

Ndufa4
22
0.5
0.634
−0.377
8.49E−05
2.27E−02

Ube2s
22
0.403
0.502
−0.395
8.53E−05
2.28E−02

Tsc22d3
22
0.543
0.407
0.418
8.71E−05
2.32E−02

Il1b
22
0.867
0.929
−0.351
9.72E−05
2.54E−02

Sertad1
22
0.265
0.149
0.664
9.82E−05
2.56E−02

Psmb8
22
0.564
0.668
−0.341
1.06E−04
2.75E−02

Usf2
22
0.278
0.383
−0.487
1.09E−04
2.80E−02

Sgms1
22
0.179
0.081
1.009
1.11E−04
2.85E−02

Gapdh
22
0.679
0.624
0.201
1.16E−04
2.96E−02

Arf2
22
0.173
0.071
1.044
1.20E−04
3.04E−02

Tuba1c
22
0.321
0.203
0.731
1.24E−04
3.14E−02

Ogfrl1
22
0.181
0.305
−0.670
1.25E−04
3.15E−02

Tsc22d1
22
0.11
0.234
−1.009
1.36E−04
3.38E−02

Bcl3
22
0.128
0.237
−0.835
1.39E−04
3.43E−02

Vasp
22
0.434
0.536
−0.432
1.41E−04
3.49E−02

Eno1
22
0.518
0.431
0.380
1.43E−04
3.54E−02

Srrm1
22
0.191
0.346
−0.711
1.44E−04
3.54E−02

Pmaip1
22
0.403
0.549
−0.422
1.45E−04
3.55E−02

Ier2
22
0.763
0.644
0.258
1.46E−04
3.58E−02

Birc3
22
0.27
0.346
−0.538
1.48E−04
3.63E−02

Smpdl3a
22
0.51
0.441
0.442
1.49E−04
3.63E−02

Csf2rb
22
0.411
0.532
−0.439
1.51E−04
3.68E−02

Smim3
22
0.245
0.353
−0.460
1.55E−04
3.76E−02

Uqcrh
22
0.806
0.759
0.180
1.63E−04
3.93E−02

Trem2
22
0.168
0.081
0.903
1.66E−04
3.98E−02

Pxdc1
22
0.102
0.21
−0.875
1.71E−04
4.10E−02

Tor3a
22
0.099
0.207
−0.772
1.72E−04
4.11E−02

Themis2
22
0.077
0.159
−1.051
1.73E−04
4.14E−02

Ltb4r1
22
0.176
0.085
0.704
1.81E−04
4.28E−02

Slc15a3
22
0.383
0.454
−0.576
1.84E−04
4.35E−02

Nabp1
22
0.186
0.305
−0.758
1.90E−04
4.46E−02

Ppfia4
22
0.306
0.451
−0.532
1.91E−04
4.49E−02

Taldo1
22
0.625
0.573
0.335
2.00E−04
4.67E−02

Eif4a2
22
0.418
0.295
0.493
2.15E−04
4.96E−02

Tnip3
23
0
0.4
−6.333
8.83E−08
5.06E−05

Psap
23
0.21
0.667
−1.655
1.11E−04
2.85E−02

Dock10
24
0.926
0.489
0.417
9.58E−05
2.51E−02

Mcpt4
26
0.911
0.357
1.787
5.23E−28
2.42E−24

Tph1
26
0.934
0.486
1.478
2.57E−27
1.14E−23

Srsf5
26
0.63
0.829
−1.082
4.98E−21
1.37E−17

Cma1
26
0.744
0.243
2.537
9.01E−19
2.03E−15

Fcer1a
26
0.99
0.943
0.660
4.49E−18
9.47E−15

Hdc
26
0.851
0.5
1.578
2.26E−17
4.45E−14

Mcpt1
26
0.926
0.514
0.960
4.48E−17
8.57E−14

Mcpt2
26
0.925
0.571
1.316
3.45E−16
6.06E−13

Jun
26
0.931
0.657
0.914
1.05E−15
1.76E−12

Rac2
26
0.967
0.943
0.602
3.12E−14
4.51E−11

Ftl1
26
1
1
0.693
1.20E−13
1.60E−10

Rhob
26
0.376
0.014
3.404
1.65E−13
2.19E−10

Lxn
26
0.462
0.071
2.252
3.85E−13
4.92E−10

Rgs13
26
0.73
0.3
1.533
1.69E−12
2.04E−09

Gzmb
26
0.745
0.729
−0.968
6.66E−12
7.38E−09

Smpx
26
0.629
0.229
1.654
7.19E−12
7.96E−09

Sla
26
0.535
0.114
1.631
8.46E−12
9.27E−09

Sox4
26
0.025
0.243
−3.162
1.51E−11
1.61E−08

Zfp36l2
26
0.897
0.643
1.135
2.91E−11
3.01E−08

Srgn
26
0.999
1
0.549
4.41E−11
4.48 E−08

Cpa3
26
0.999
0.986
0.828
7.69E−11
7.52E−08

Ranbp1
26
0.357
0.629
−0.883
9.59E−11
9.26E−08

Tgm2
26
0.011
0.186
−3.066
1.04E−10
1.00E−07

Ninj1
26
0.254
0.6
−1.060
1.42E−10
1.34E−07

Cnbp
26
0.626
0.857
−0.661
1.96E−10
1.81E−07

Cited2
26
0.8
0.471
1.214
2.62E−10
2.38E−07

Mcpt8
26
0.171
0.457
−0.992
2.92E−10
2.64E−07

Btg2
26
0.23
0.571
−1.300
5.60E−10
4.82E−07

Hmgn1
26
0.23
0.486
−1.120
9.79E−10
8.16E−07

Oaf
26
0.524
0.157
1.769
1.28E−09
1.04E−06

Klf2
26
0.452
0.129
2.040
1.72E−09
1.36E−06

Mif
26
0.297
0.5
−0.971
1.88E−09
1.48E−06

Cst3
26
0.861
0.629
0.718
2.95E−09
2.22E−06

Dnaja1
26
0.545
0.7
−0.770
3.19E−09
2.38E−06

Ncl
26
0.46
0.671
−0.777
3.37E−09
2.51E−06

Il1rl1
26
0.755
0.443
1.096
4.41E−09
3.20E−06

Serpinb1a
26
0.826
0.571
1.037
6.33E−09
4.49E−06

Ero1l
26
0.676
0.357
1.295
8.15E−09
5.69E−06

Zfp36
26
0.673
0.343
1.037
1.18E−08
7.97E−06

Sub1
26
0.943
0.971
−0.456
3.26E−08
2.05E−05

Srsf6
26
0.347
0.6
−0.812
3.47E−08
2.16E−05

Srsf2
26
0.413
0.529
−0.824
3.56E−08
2.21E−05

Phlda1
26
0.409
0.1
2.714
5.58E−08
3.33E−05

Mctp1
26
0.419
0.129
1.488
5.82E−08
3.46E−05

Crip1
26
0.883
0.743
0.753
6.64E−08
3.90E−05

Spint2
26
0.088
0.314
−1.410
6.72E−08
3.93E−05

Ctla2a
26
0.18
0
4.696
6.75E−08
3.95E−05

Hic1
26
0.252
0.543
−1.130
7.28E−08
4.24E−05

Srrm2
26
0.369
0.614
−0.891
8.77E−08
5.03E−05

Cirbp
26
0.334
0.571
−0.866
8.94E−08
5.12E−05

Tpsb2
26
0.237
0.029
4.861
9.22E−08
5.26E−05

Tmem64
26
0.346
0.057
1.990
1.20E−07
6.78E−05

Npc2
26
0.789
0.6
0.654
1.21E−07
6.84E−05

Klf6
26
0.581
0.329
1.376
1.64E−07
9.03E−05

Hspa1a
26
0.166
0
5.537
1.77E−07
9.65E−05

Vim
26
0.626
0.343
0.759
1.88E−07
1.02E−04

Eif5a
26
0.721
0.786
−0.446
2.15E−07
1.15E−04

Furin
26
0.945
0.871
0.737
2.23E−07
1.19E−04

Gadd45a
26
0.273
0.6
−0.836
2.42E−07
1.29E−04

Tgif1
26
0.046
0.243
−1.699
2.49E−07
1.32E−04

H2-D1
26
0.896
0.957
−0.482
2.71E−07
1.43E−04

Tsc22d3
26
0.662
0.357
1.032
2.94E−07
1.53E−04

Magohb
26
0.165
0.429
−1.075
3.01E−07
1.57E−04

Igkv1-135
26
0.033
0.2
−1.693
3.48E−07
1.78E−04

Gpr132
26
0.057
0.271
−1.568
4.28E−07
2.16E−04

Kdelr1
26
0.317
0.071
1.679
5.15E−07
2.57E−04

Il4ra
26
0.147
0.286
−1.265
5.76E−07
2.83E−04

Ebi3
26
0.161
0
4.036
5.83E−07
2.87E−04

Cyp11a1
26
0.899
0.786
0.600
7.08E−07
3.41E−04

Errfi1
26
0.365
0.529
−0.821
7.10E−07
3.42E−04

Plxdc2
26
0.163
0
3.918
7.20E−07
3.45E−04

Slc7a8
26
0.37
0.129
1.625
9.70E−07
4.52E−04

Eif4a1
26
0.773
0.814
−0.432
1.12E−06
5.13E−04

Cst7
26
0.665
0.4
0.794
1.16E−06
5.32E−04

Gpr171
26
0.608
0.343
1.297
1.45E−06
6.45E−04

Rnf128
26
0.374
0.1
1.404
1.78E−06
7.77E−04

H2-K1
26
0.642
0.771
−0.585
1.84E−06
7.97E−04

Cish
26
0.397
0.1
1.408
1.92E−06
8.25E−04

H3f3b
26
0.996
0.986
−0.452
1.92E−06
8.25E−04

Fam105a
26
0.73
0.557
0.743
2.06E−06
8.80E−04

Malat1
26
0.999
1
−0.422
2.21E−06
9.37E−04

Neurl3
26
0.389
0.643
−0.790
2.58E−06
1.07E−03

Egr1
26
0.849
0.614
0.220
2.58E−06
1.07E−03

Map1lc3a
26
0.378
0.514
−0.642
2.71E−06
1.12E−03

Sec11c
26
0.715
0.514
0.729
2.79E−06
1.15E−03

Pnrc1
26
0.562
0.771
−0.684
2.83E−06
1.16E−03

Lgals1
26
0.7
0.429
0.520
3.68E−06
1.46E−03

Lilrb4a
26
0.598
0.3
0.964
4.14E−06
1.62E−03

Pilrb2
26
0.263
0.043
1.825
4.67E−06
1.81E−03

Actg1
26
0.976
0.914
0.322
5.47E−06
2.08E−03

Ddit4
26
0.369
0.129
1.501
5.56E−06
2.11E−03

Cyb5a
26
0.509
0.243
0.906
6.23E−06
2.34E−03

Ccl2
26
0.455
0.186
1.605
7.97E−06
2.91E−03

Slc30a2
26
0.206
0.029
1.497
7.99E−06
2.91E−03

Vwa5a
26
0.338
0.1
1.596
8.14E−06
2.96E−03

Gsn
26
0.437
0.186
1.055
8.80E−06
3.18E−03

Mat2a
26
0.378
0.6
−0.741
8.83E−06
3.18E−03

Srsf7
26
0.374
0.557
−0.602
9.23E−06
3.32E−03

Cd200r3
26
0.267
0.057
1.849
1.17E−05
4.10E−03

Mt1
26
0.522
0.257
1.064
1.18E−05
4.12E−03

Patz1
26
0.154
0.314
−0.988
1.39E−05
4.77E−03

Tyrobp
26
0.955
0.929
0.395
1.43E−05
4.89E−03

Cbx1
26
0.184
0.329
−0.828
1.51E−05
5.12E−03

Ccnd2
26
0.346
0.443
−0.674
1.61E−05
5.42E−03

Emd
26
0.206
0.314
−1.086
1.61E−05
5.43E−03

Rgs1
26
0.84
0.6
0.590
1.65E−05
5.55E−03

Impdh2
26
0.211
0.371
−0.895
1.81E−05
6.00E−03

Optn
26
0.213
0.029
2.198
1.98E−05
6.48E−03

Opa3
26
0.089
0.257
−1.429
2.12E−05
6.88E−03

Mns1
26
0.338
0.143
1.231
2.32E−05
7.41E−03

Itm2b
26
0.987
0.971
0.287
2.44E−05
7.76E−03

Adora3
26
0.431
0.186
0.909
2.50E−05
7.90E−03

Pim3
26
0.145
0.371
−1.317
2.62E−05
8.21E−03

Tmem9
26
0.437
0.229
0.978
2.95E−05
9.14E−03

Eif3h
26
0.84
0.686
0.444
2.96E−05
9.16E−03

1810058l24Rik
26
0.625
0.386
0.587
3.04E−05
9.37E−03

Hspa8
26
0.953
0.843
0.375
3.06E−05
9.43E−03

Alox5ap
26
0.762
0.543
0.807
3.09E−05
9.49E−03

Coq10b
26
0.226
0.314
−0.675
3.54E−05
1.07E−02

Fam174a
26
0.201
0.4
−0.766
3.59E−05
1.09E−02

Spag9
26
0.153
0.343
−1.004
4.00E−05
1.19E−02

Fbxo9
26
0.144
0.171
−0.681
4.12E−05
1.22E−02

H3f3a
26
0.885
0.9
−0.310
4.35E−05
1.28E−02

Ndufa6
26
0.865
0.729
0.485
4.60E−05
1.35E−02

Pik3r6
26
0.366
0.129
0.880
4.81E−05
1.40E−02

Ptp4a1
26
0.354
0.543
−0.748
5.01E−05
1.45E−02

Dot1l
26
0.088
0.2
−1.211
5.22E−05
1.50E−02

Cited4
26
0.891
0.829
−0.273
5.73E−05
1.63E−02

F2r
26
0.389
0.157
1.091
6.05E−05
1.70E−02

Snrpb
26
0.546
0.7
−0.456
6.05E−05
1.70E−02

Lif
26
0.174
0.014
3.225
6.63E−05
1.84E−02

Nmrk1
26
0.043
0.186
−1.576
6.82E−05
1.89E−02

Homer2
26
0.293
0.086
1.493
6.90E−05
1.91E−02

Adgre5
26
0.304
0.1
1.018
7.15E−05
1.96E−02

Ctsc
26
0.701
0.471
0.858
7.46E−05
2.04E−02

Ddx5
26
0.943
0.986
−0.374
7.71E−05
2.10E−02

Kcnq1ot1
26
0.101
0.243
−1.171
7.75E−05
2.11E−02

Zcrb1
26
0.343
0.586
−0.574
8.17E−05
2.20E−02

Deptor
26
0.119
0.329
−1.074
8.21E−05
2.21E−02

Dcaf12
26
0.143
0.357
−0.920
8.27E−05
2.22E−02

Myeov2
26
0.826
0.614
0.406
8.54E−05
2.28E−02

Il6
26
0.356
0.114
1.578
8.97E−05
2.38E−02

Tubb2b
26
0.164
0.043
0.556
9.08E−05
2.40E−02

Rrp15
26
0.056
0.214
−1.304
9.41E−05
2.47E−02

Lmo4
26
0.407
0.571
−0.744
9.80E−05
2.56E−02

Creg1
26
0.699
0.514
0.693
1.02E−04
2.64E−02

Cuedc1
26
0.166
0.4
−0.928
1.06E−04
2.74E−02

Nucb1
26
0.396
0.171
0.953
1.16E−04
2.95E−02

Zcchc10
26
0.409
0.186
1.098
1.26E−04
3.17E−02

Zfp131
26
0.106
0.271
−1.115
1.27E−04
3.21E−02

Smco4
26
0.629
0.386
0.580
1.28E−04
3.21E−02

Nhp2l1
26
0.382
0.514
−0.624
1.28E−04
3.22E−02

Snrpd3
26
0.37
0.429
−0.444
1.32E−04
3.30E−02

Ifitm3
26
0.169
0.314
−0.813
1.32E−04
3.31E−02

Rac1
26
0.703
0.486
0.575
1.33E−04
3.32E−02

Cox4i1
26
0.948
0.886
0.320
1.35E−04
3.37E−02

Plscr1
26
0.553
0.286
0.843
1.45E−04
3.55E−02

Ccdc107
26
0.202
0.3
−0.711
1.45E−04
3.56E−02

Zfos1
26
0.264
0.3
−0.542
1.46E−04
3.58E−02

Rexo2
26
0.745
0.557
0.602
1.48E−04
3.62E−02

Bhlhe40
26
0.433
0.186
1.174
1.52E−04
3.70E−02

Tsc22d1
26
0.739
0.843
−0.468
1.55E−04
3.76E−02

Ctsg
26
0.117
0.3
−0.877
1.56E−04
3.78E−02

Nfkbid
26
0.664
0.386
0.823
1.56E−04
3.78E−02

Actb
26
0.999
1
0.617
1.72E−04
4.11E−02

Bcl2l11
26
0.035
0.157
−1.690
1.74E−04
4.15E−02

Ecm1
26
0.301
0.086
1.528
1.81E−04
4.29E−02

Serf2
26
0.979
0.971
0.319
1.86E−04
4.39E−02

Dnajc2
26
0.14
0.271
−0.988
1.96E−04
4.57E−02

Neat1
26
0.735
0.543
0.449
1.97E−04
4.61E−02

Eif3g
26
0.315
0.457
−0.628
1.99E−04
4.65E−02

Dusp2
27
0.396
0.152
1.356
9.49E−05
2.49E−02

Btg2
3
0.826
0.969
−0.826
2.71E−113
5.25E−108

Junb
3
0.945
0.99
−0.529
8.39E−66
3.05E−61

Ubb
3
0.96
0.994
−0.435
1.78E−62
4.32E−58

Dusp1
3
0.55
0.847
−0.794
2.66E−59
5.33E−55

Bcl2
3
0.592
0.355
0.931
2.24E−56
4.35E−52

Pnrc1
3
0.567
0.824
−0.650
1.08E−54
1.84E−50

Pim1
3
0.402
0.691
−0.806
8.46E−53
1.37E−48

Jund
3
0.851
0.964
−0.536
1.29E−48
1.70E−44

Actg1
3
0.92
0.875
0.331
1.42E−47
1.80E−43

Btg1
3
0.808
0.931
−0.523
2.11E−46
2.51E−42

Irf7
3
0.149
0.388
−1.262
8.63E−45
9.13E−41

Ppp1r15a
3
0.237
0.503
−0.934
2.94E−41
2.72E−37

Zfp36l2
3
0.47
0.246
0.933
1.12E−40
9.99E−37

Fosb
3
0.211
0.462
−1.004
2.21E−38
1.76E−34

Hk2
3
0.23
0.445
−0.999
4.43E−36
3.26E−32

Nfkbia
3
0.533
0.795
−0.622
9.05E−36
6.50E−32

Gadd45b
3
0.264
0.518
−0.881
1.36E−35
9.65E−32

Klf4
3
0.133
0.346
−1.042
4.12E−34
2.70E−30

Dusp2
3
0.235
0.07
1.410
4.13E−34
2.70E−30

Cd69
3
0.493
0.703
−0.730
4.86E−34
3.14E−30

Fos
3
0.611
0.828
−0.558
1.81E−31
1.03E−27

B930036N10Rik
3
0.147
0.322
−1.297
7.30E−31
4.01E−27

Slc7a6os
3
0.156
0.356
−1.073
4.21E−30
2.17E−26

Igkc
3
0.993
0.99
0.322
2.50E−28
1.20E−24

Tiparp
3
0.039
0.182
−1.581
5.71E−28
2.62E−24

Eif1
3
0.99
1
−0.260
3.15E−27
1.39E−23

Sla
3
0.716
0.658
0.317
1.28E−26
5.50E−23

Rsrp1
3
0.466
0.665
−0.640
5.63E−26
2.26E−22

Bhlhe40
3
0.438
0.633
−0.573
5.97E−26
2.38E−22

Igha
3
0.966
0.943
0.291
2.18E−25
8.41E−22

Tgif1
3
0.254
0.444
−0.724
7.91E−25
2.93E−21

Prr7
3
0.076
0.223
−1.236
9.69E−25
3.57E−21

Klrk1
3
0.546
0.684
−0.499
9.42E−24
3.19E−20

Tnfaip3
3
0.301
0.489
−0.677
5.84E−22
1.68E−18

Clk1
3
0.338
0.518
−0.578
3.00E−21
8.35E−18

Ier2
3
0.685
0.822
−0.556
5.05E−21
1.38E−17

Ifrd1
3
0.183
0.357
−0.754
3.81E−20
9.81E−17

Txnip
3
0.202
0.084
1.079
9.16E−20
2.29E−16

Lpar6
3
0.24
0.401
−0.676
1.77E−19
4.30E−16

Uhrf2
3
0.298
0.465
−0.609
6.32E−19
1.45E−15

Dok1
3
0.318
0.207
0.534
1.78E−18
3.91E−15

Pabpc1
3
0.698
0.855
−0.452
2.17E−18
4.72E−15

Ikzf2
3
0.438
0.561
−0.451
2.44E−18
5.29E−15

Ptpn22
3
0.521
0.39
0.465
2.81E−18
6.03E−15

Nfkbid
3
0.191
0.371
−0.763
5.78E−18
1.21E−14

Iglc1
3
0.184
0.359
−0.525
9.64E−18
1.96E−14

Hsp90aa1
3
0.394
0.326
0.558
7.02E−17
1.30E−13

Il22
3
0.082
0.207
−1.460
6.26E−16
1.08E−12

Phlda1
3
0.194
0.355
−0.587
1.73E−15
2.87E−12

Dusp5
3
0.48
0.644
−0.437
3.57E−15
5.74E−12

Cebpb
3
0.518
0.409
0.434
3.87E−15
6.20E−12

Nr4a1
3
0.458
0.63
−0.503
4.34E−15
6.90E−12

Sqstm1
3
0.227
0.375
−0.607
1.49E−14
2.25E−11

Il2rg
3
0.543
0.701
−0.419
2.42E−14
3.58E−11

Icos
3
0.271
0.421
−0.530
6.75E−14
9.42E−11

Nfil3
3
0.067
0.176
−0.989
1.01E−13
1.37E−10

Gimap9
3
0.372
0.268
0.441
1.09E−13
1.47E−10

Ier5
3
0.375
0.535
−0.499
2.92E−13
3.77E−10

Actb
3
0.956
0.953
0.237
5.27E−13
6.60E−10

Rgs1
3
0.597
0.74
−0.469
8.80E−13
1.09E−09

Hexim1
3
0.059
0.153
−0.847
1.04E−12
1.28E−09

Zc3h12a
3
0.138
0.256
−0.676
1.93E−12
2.31E−09

Cited2
3
0.137
0.264
−0.735
2.07E−12
2.47E−09

Serpinb6b
3
0.51
0.392
0.341
4.27E−12
4.85E−09

Hspa5
3
0.399
0.54
−0.437
7.57E−11
7.43E−08

Pik3r1
3
0.586
0.474
0.297
1.03E−10
9.92E−08

Herpud1
3
0.135
0.253
−0.667
2.34E−10
2.14E−07

Fam110a
3
0.101
0.199
−0.786
2.47E−10
2.25E−07

Csrnp1
3
0.185
0.311
−0.660
2.78E−10
2.52E−07

Nfkbiz
3
0.248
0.38
−0.505
3.16E−10
2.83E−07

Litaf
3
0.314
0.213
0.440
3.41E−10
3.04E−07

Asb2
3
0.402
0.563
−0.590
3.70E−10
3.26E−07

Sh2d2a
3
0.273
0.226
0.342
4.26E−10
3.70E−07

Cish
3
0.264
0.189
0.423
8.15E−10
6.87E−07

Ccnl1
3
0.276
0.43
−0.536
1.11E−09
9.06E−07

Eef2
3
0.841
0.891
−0.269
1.48E−09
1.18E−06

Chd2
3
0.134
0.241
−0.663
1.90E−09
1.49E−06

Il2rb
3
0.468
0.389
0.286
3.01E−09
2.26E−06

Nrip1
3
0.379
0.492
−0.314
3.68E−09
2.71E−06

Hsp90ab1
3
0.579
0.551
0.247
4.22E−09
3.07E−06

H2-Q7
3
0.183
0.299
−0.562
4.85E−09
3.50E−06

Tnf
3
0.155
0.272
−0.594
5.24E−09
3.76E−06

BC031181
3
0.458
0.531
−0.307
6.68E−09
4.74E−06

Uqcrh
3
0.733
0.699
0.168
6.75E−09
4.78E−06

Ptp4a1
3
0.188
0.286
−0.533
1.15E−08
7.84E−06

Ccl4
3
0.165
0.099
0.609
1.39E−08
9.32E−06

Txk
3
0.529
0.64
−0.289
1.39E−08
9.32E−06

Kdm6b
3
0.234
0.346
−0.450
1.48E−08
9.88E−06

Slc3a2
3
0.464
0.422
0.275
1.49E−08
9.95E−06

Tnfrsf18
3
0.378
0.306
0.282
1.85E−08
1.22E−05

Peli1
3
0.155
0.256
−0.536
2.62E−08
1.68E−05

Rbm3
3
0.669
0.775
−0.346
4.08 E−08
2.49E−05

Rasgrp1
3
0.184
0.281
−0.495
4.40E−08
2.68E−05

Hbp1
3
0.083
0.155
−0.641
4.76E−08
2.88E−05

Pcf11
3
0.084
0.166
−0.699
4.80E−08
2.89E−05

Tns4
3
0.147
0.258
−0.647
5.88E−08
3.49E−05

Rora
3
0.552
0.617
−0.268
6.69E−08
3.92E−05

Prdx6
3
0.719
0.67
0.153
7.69E−08
4.47E−05

Gpr65
3
0.176
0.111
0.508
8.15E−08
4.69E−05

Tpm4
3
0.398
0.34
0.239
9.64E−08
5.48E−05

Tnfsf11
3
0.24
0.166
0.430
1.25E−07
7.00E−05

Abi3
3
0.22
0.36
−0.553
1.32E−07
7.38E−05

Samsn1
3
0.449
0.381
0.225
1.35E−07
7.51E−05

Oser1
3
0.273
0.379
−0.404
1.52E−07
8.39E−05

Gpr171
3
0.279
0.22
0.298
1.76E−07
9.61E−05

Traf1
3
0.319
0.395
−0.340
2.26E−07
1.21E−04

Tuba1a
3
0.118
0.21
−0.674
2.35E−07
1.25E−04

Sla2
3
0.27
0.204
0.330
3.15E−07
1.63E−04

Ccng2
3
0.12
0.205
−0.558
3.26E−07
1.68E−04

5031425E22Rik
3
0.202
0.311
−0.472
4.05E−07
2.06E−04

Cmas
3
0.196
0.305
−0.539
4.14E−07
2.10E−04

Lmo4
3
0.583
0.682
−0.256
6.18E−07
3.02E−04

Tgoln1
3
0.222
0.334
−0.444
6.36E−07
3.09E−04

Erdr1
3
0.118
0.184
−0.515
6.51E−07
3.16E−04

Emb
3
0.794
0.827
−0.232
6.91E−07
3.33E−04

Ubc
3
0.343
0.46
−0.304
8.30E−07
3.92E−04

Pcbp2
3
0.491
0.633
−0.325
8.47E−07
3.99E−04

4930523C07Rik
3
0.185
0.281
−0.469
9.87E−07
4.60E−04

Tle3
3
0.189
0.125
0.507
1.00E−06
4.65E−04

Il16
3
0.087
0.161
−0.633
1.30E−06
5.87E−04

Sft2d2
3
0.174
0.114
0.455
1.32E−06
5.95E−04

Sepp1
3
0.849
0.899
−0.270
1.33E−06
6.00E−04

H2-K1
3
0.828
0.897
−0.269
1.35E−06
6.04E−04

Birc3
3
0.144
0.22
−0.453
1.63E−06
7.17E−04

Tmem243
3
0.21
0.305
−0.402
1.87E−06
8.10E−04

Vps37b
3
0.49
0.514
−0.262
2.55E−06
1.06E−03

Ptprcap
3
0.625
0.568
0.175
2.86E−06
1.17E−03

Serinc3
3
0.202
0.143
0.464
3.66E−06
1.45E−03

Gltscr2
3
0.468
0.572
−0.269
3.86E−06
1.52E−03

Rsl24d1
3
0.164
0.111
0.429
4.20E−06
1.64E−03

Maff
3
0.385
0.446
−0.284
4.62E−06
1.79E−03

Npc2
3
0.496
0.457
0.158
5.10E−06
1.96E−03

Acpp
3
0.093
0.162
−0.600
5.45E−06
2.08E−03

Ppt2
3
0.361
0.309
0.209
5.74E−06
2.18E−03

Gcnt2
3
0.13
0.203
−0.416
5.76E−06
2.18E−03

Pnisr
3
0.213
0.314
−0.367
6.48E−06
2.42E−03

D16Ertd472e
3
0.136
0.223
−0.475
6.49E−06
2.43E−03

Gna13
3
0.265
0.348
−0.321
7.31E−06
2.70E−03

Socs1
3
0.271
0.231
0.281
8.07E−06
2.94E−03

Ifngr1
3
0.725
0.673
0.162
1.11E−05
3.90E−03

H2-D1
3
0.979
0.99
−0.188
1.20E−05
4.17E−03

Hilpda
3
0.404
0.527
−0.321
1.25E−05
4.32E−03

Fam102a
3
0.219
0.169
0.330
1.33E−05
4.57E−03

Crem
3
0.369
0.289
0.312
1.43E−05
4.89E−03

Rinl
3
0.465
0.388
0.248
1.45E−05
4.95E−03

Spop
3
0.205
0.301
−0.398
1.63E−05
5.47E−03

Jchain
3
0.781
0.732
0.156
1.70E−05
5.67E−03

F2r
3
0.258
0.36
−0.384
1.71E−05
5.70E−03

Rgs2
3
0.37
0.466
−0.291
1.72E−05
5.73E−03

Ahr
3
0.268
0.205
0.390
1.82E−05
6.02E−03

Ndufs4
3
0.293
0.238
0.222
1.98E−05
6.48E−03

Hes1
3
0.093
0.176
−0.774
2.01E−05
6.56E−03

Ddx18
3
0.188
0.159
0.252
2.36E−05
7.53E−03

Eprs
3
0.127
0.202
−0.476
2.38E−05
7.59E−03

Rara
3
0.1
0.17
−0.564
2.43E−05
7.72E−03

Prelid2
3
0.323
0.269
0.243
3.05E−05
9.40E−03

Clcn3
3
0.202
0.277
−0.363
3.20E−05
9.81E−03

Tbx21
3
0.185
0.137
0.344
3.22E−05
9.86E−03

Exosc3
3
0.167
0.125
0.348
3.25E−05
9.91E−03

Ppp1r10
3
0.19
0.274
−0.337
3.60E−05
1.09E−02

Cbx3
3
0.276
0.238
0.168
3.94E−05
1.18E−02

Rnf19b
3
0.173
0.231
−0.353
4.11E−05
1.22E−02

Ccdc174
3
0.11
0.167
−0.475
4.11E−05
1.22E−02

Gimap5
3
0.45
0.395
0.168
4.82E−05
1.40E−02

Dgat1
3
0.306
0.404
−0.324
4.90E−05
1.42E−02

Plk3
3
0.177
0.143
0.331
5.41E−05
1.55E−02

H2-Q4
3
0.167
0.254
−0.495
6.01E−05
1.70E−02

Znhit1
3
0.188
0.154
0.272
6.69E−05
1.85E−02

Nop56
3
0.089
0.162
−0.544
7.45E−05
2.03E−02

Neurl3
3
0.314
0.382
−0.256
7.70E−05
2.10E−02

Il18r1
3
0.431
0.465
−0.175
8.60E−05
2.29E−02

Mbd2
3
0.209
0.314
−0.452
8.79E−05
2.34E−02

Tubb4b
3
0.138
0.233
−0.547
8.85E−05
2.35E−02

Dtx3
3
0.185
0.275
−0.378
9.21E−05
2.42E−02

Slc38a2
3
0.12
0.186
−0.469
9.33E−05
2.45E−02

Ehd1
3
0.158
0.119
0.345
1.13E−04
2.90E−02

Abhd2
3
0.286
0.24
0.335
1.13E−04
2.90E−02

Zc3hav1
3
0.163
0.248
−0.395
1.22E−04
3.09E−02

Dtx1
3
0.173
0.251
−0.367
1.22E−04
3.09E−02

Nfkb2
3
0.103
0.165
−0.512
1.35E−04
3.36E−02

Gem
3
0.463
0.509
−0.304
1.38E−04
3.42E−02

Bcl2a1d
3
0.344
0.394
−0.236
1.43E−04
3.53E−02

Xbp1
3
0.31
0.282
0.218
1.50E−04
3.67E−02

Slc16a6
3
0.233
0.309
−0.365
1.52E−04
3.69E−02

Cdc42se2
3
0.198
0.283
−0.363
1.53E−04
3.72E−02

Clta
3
0.37
0.32
0.163
1.78E−04
4.24E−02

Ahcyl2
3
0.515
0.469
0.214
1.83E−04
4.33E−02

Saraf
3
0.394
0.493
−0.258
1.85E−04
4.36E−02

Tgfb1
3
0.268
0.361
−0.366
2.06E−04
4.79E−02

Cnot2
3
0.089
0.154
−0.535
2.10E−04
4.87E−02

Ighg1
31
0.165
0
4.475
1.46E−06
6.53E−04

Ifi30
31
0.417
0.274
1.031
3.76E−06
1.48E−03

Cyba
31
0.626
0.453
0.749
1.25E−05
4.35E−03

AW112010
31
0.087
0.379
−0.682
1.66E−05
5.56E−03

Ppia
31
0.904
0.768
0.300
1.91E−05
6.27E−03

Tmem258
31
0.4
0.368
0.478
4.81E−05
1.40E−02

Mif
31
0.461
0.232
0.781
1.24E−04
3.14E−02

H2-DMb2
31
0.617
0.421
0.572
1.73E−04
4.14E−02

1600010M07Rik
31
0.017
0.189
−2.290
1.78E−04
4.24E−02

Npm1
31
0.661
0.505
0.488
1.79E−04
4.25E−02

Cebpb
33
1
0.528
2.572
8.08E−08
4.66E−05

Nr4a1
33
1
0.167
3.626
5.30E−07
2.63E−04

Errfi1
33
1
0.153
4.176
8.06E−07
3.82E−04

Mt1
33
1
0.694
3.108
1.08E−06
5.00E−04

Thbs1
33
1
0.111
3.767
2.94E−06
1.20E−03

Ccl7
33
0.8
0
7.280
1.34E−05
4.62E−03

Mt2
33
0.8
0.347
2.965
1.81E−05
5.99E−03

Hspa8
33
1
0.806
0.917
5.18E−05
1.49E−02

Cyr61
33
1
0.264
2.237
7.96E−05
2.15E−02

Vmp1
33
1
0.389
2.516
1.37E−04
3.40E−02

Mylk
33
0.8
0.417
1.983
1.48E−04
3.63E−02

Csrnp1
33
0.6
0.014
4.333
1.84E−04
4.35E−02

Cxcl1
33
0.6
0.014
4.780
2.16E−04
4.98E−02

Klf6
34
1
0.444
1.381
3.64E−06
1.44E−03

Dusp1
34
1
0.944
1.553
1.30E−05
4.49E−03

Jun
34
0.815
0.556
1.650
1.41E−05
4.84E−03

Hp
34
0.778
0.111
2.076
2.60E−05
8.17E−03

Zfp36
34
1
0.944
1.022
2.61E−05
8.19E−03

Actg1
34
1
1
0.491
3.69E−05
1.11E−02

Osm
34
0.63
0.111
3.025
6.22E−05
1.74E−02

2700029M09Rik
34
0.111
0.722
−1.619
7.03E−05
1.94E−02

Ctsd
34
0.593
0.611
1.128
8.03E−05
2.17E−02

Oas1a
34
0
0.333
−4.376
1.99E−04
4.65E−02

Pkp3
34
0.296
0
4.344
2.09E−04
4.84E−02

Dusp1
36
0.981
0.944
1.061
1.05E−09
8.69E−07

Cxcl2
36
0.879
0.5
2.134
2.52E−08
1.62E−05

Zfp36
36
0.873
0.444
1.362
4.84E−07
2.42E−04

Btg1
36
0.943
0.944
−0.853
7.36E−06
2.71E−03

Junb
36
0.994
0.889
0.761
1.05E−05
3.70E−03

Fos
36
0.815
0.556
0.893
3.16E−05
9.69E−03

Ccr12
36
0.924
0.556
0.948
3.33E−05
1.01E−02

Osm
36
0.554
0.056
3.512
4.40E−05
1.30E−02

Psmb3
36
0.076
0.5
−1.766
6.03E−05
1.70E−02

Plac8
36
0.083
0.5
−2.336
7.78E−05
2.11E−02

Laptm5
36
0.248
0.778
−1.097
1.30E−04
3.25E−02

Nfkbia
36
0.86
0.556
1.136
1.79E−04
4.25E−02

Nfkbiz
36
0.605
0.167
1.880
2.08E−04
4.84E−02

Sla
4
0.794
0.538
0.969
2.51E−32
1.48E−28

Hspa1a
4
0.242
0.016
3.237
3.38E−32
1.97E−28

Vps37b
4
0.458
0.761
−0.984
1.98E−30
1.04E−26

Ifrd1
4
0.334
0.632
−1.143
7.30E−29
3.60E−25

Jund
4
0.892
0.983
−0.446
6.06E−28
2.75E−24

Junb
4
0.974
1
−0.294
1.32E−23
4.41E−20

Fosb
4
0.434
0.725
−0.828
1.90E−22
5.73E−19

Crem
4
0.324
0.608
−1.068
2.14E−21
5.98E−18

Ighg1
4
0.152
0.009
2.835
6.74E−20
1.70E−16

Pim1
4
0.555
0.787
−0.650
9.41E−20
2.34E−16

Maff
4
0.53
0.798
−0.559
2.54E−19
6.10E−16

Eif1
4
0.995
0.997
−0.261
5.38E−19
1.25E−15

Bcl2
4
0.83
0.631
0.595
9.99E−19
2.24E−15

Klf4
4
0.249
0.528
−0.915
8.57E−18
1.76E−14

Hsp90aa1
4
0.591
0.434
0.823
9.70E−18
1.97E−14

Ubc
4
0.352
0.611
−0.751
1.24E−17
2.51E−14

Emb
4
0.625
0.777
−0.562
1.30E−17
2.60E−14

Tnfaip3
4
0.452
0.711
−0.653
5.35E−17
1.01E−13

Prr7
4
0.129
0.368
−1.231
6.59E−17
1.23E−13

Ncoa7
4
0.717
0.495
0.664
1.73E−16
3.10E−13

Lmna
4
0.198
0.422
−1.142
5.25E−16
9.14E−13

Fam110a
4
0.308
0.526
−0.910
8.04E−16
1.37E−12

Cwc25
4
0.082
0.286
−1.528
1.08E−15
1.80E−12

Bhlhe40
4
0.555
0.761
−0.529
2.89E−15
4.70E−12

Igkc
4
0.992
0.993
0.522
1.54E−14
2.32E−11

Rasl11a
4
0.563
0.34
0.883
2.96E−14
4.33E−11

Hsp90ab1
4
0.71
0.639
0.576
4.53E−14
6.42E−11

Tgif1
4
0.442
0.66
−0.551
1.85E−13
2.45E−10

Pnrc1
4
0.73
0.855
−0.435
7.84E−13
9.73E−10

Sqstm1
4
0.365
0.566
−0.648
1.97E−12
2.35E−09

Dnajb1
4
0.316
0.152
1.254
2.45E−12
2.87E−09

Ptpn22
4
0.437
0.251
0.859
4.74E−12
5.38E−09

Ccng2
4
0.239
0.463
−0.679
4.86E−12
5.50E−09

Zc3h12a
4
0.27
0.479
−0.761
7.63E−12
8.41E−09

Rilpl2
4
0.237
0.077
1.286
9.02E−12
9.85E−09

Nabp1
4
0.357
0.568
−0.645
1.97E−11
2.08E−08

Ube2s
4
0.432
0.648
−0.485
3.44E−11
3.54E−08

Srsf2
4
0.527
0.62
−0.468
3.68E−11
3.77E−08

Atf3
4
0.113
0.291
−1.066
4.69E−11
4.72E−08

Phlda1
4
0.288
0.507
−0.547
5.57E−11
5.57E−08

Btg2
4
0.835
0.958
−0.231
7.48E−11
7.37E−08

Saraf
4
0.432
0.622
−0.530
7.86E−11
7.68E−08

Gimap1
4
0.56
0.343
0.584
1.23E−10
1.17E−07

Hspe1
4
0.512
0.362
0.670
1.77E−10
1.65E−07

Coq10b
4
0.298
0.497
−0.674
2.49E−10
2.27E−07

Hspa8
4
0.861
0.831
0.431
5.85E−10
5.00E−07

Gna13
4
0.254
0.443
−0.674
6.56E−10
5.56E−07

H2-D1
4
0.977
0.99
−0.231
8.63E−10
7.27E−07

Tcrg-C1
4
0.326
0.136
1.027
1.08E−09
8.87E−07

Uhrf2
4
0.545
0.706
−0.558
1.17E−09
9.57E−07

Dot1l
4
0.054
0.181
−1.046
1.19E−09
9.71E−07

Srgn
4
0.738
0.617
0.492
1.38E−09
1.10E−06

Dusp1
4
0.71
0.841
−0.424
3.19E−09
2.38E−06

Ptp4a1
4
0.265
0.43
−0.687
3.62E−09
2.68E−06

4930523C07Rik
4
0.365
0.51
−0.605
8.93E−09
6.17E−06

Gltscr2
4
0.524
0.659
−0.495
1.16E−08
7.84E−06

Rbm3
4
0.635
0.754
−0.399
1.40E−08
9.37E−06

Emd
4
0.244
0.409
−0.653
1.55E−08
1.03E−05

Dgat1
4
0.491
0.66
−0.450
1.66E−08
1.10E−05

Neurl3
4
0.26
0.448
−0.600
2.15E−08
1.40E−05

Gpx1
4
0.763
0.76
−0.322
2.94E−08
1.86E−05

Gimap5
4
0.409
0.232
0.701
3.55E−08
2.21E−05

Mmd
4
0.35
0.19
0.817
4.03E−08
2.47E−05

Neat1
4
0.386
0.289
0.600
4.81E−08
2.90E−05

Hspa5
4
0.568
0.69
−0.402
7.66E−08
4.46E−05

Gpr183
4
0.357
0.51
−0.523
9.52E−08
5.42E−05

Ppp1r15a
4
0.329
0.493
−0.513
1.21E−07
6.84E−05

Tiparp
4
0.049
0.153
−1.235
1.28E−07
7.14E−05

Il2rg
4
0.64
0.791
−0.301
1.60E−07
8.79E−05

Il4ra
4
0.069
0.193
−1.110
1.75E−07
9.59E−05

Arg1
4
0.28
0.138
1.029
2.02E−07
1.09E−04

Hk2
4
0.226
0.378
−0.726
2.03E−07
1.10E−04

B2m
4
0.992
0.986
−0.174
2.28E−07
1.22E−04

Pop4
4
0.051
0.16
−1.155
3.07E−07
1.60E−04

Ahr
4
0.211
0.099
0.979
3.29E−07
1.70E−04

Cish
4
0.221
0.092
1.037
4.61E−07
2.31E−04

Gpr132
4
0.56
0.726
−0.351
4.68E−07
2.35E−04

Nfkbia
4
0.743
0.866
−0.242
5.88E−07
2.89E−04

Atf4
4
0.347
0.47
−0.529
6.24E−07
3.05E−04

Arf4
4
0.476
0.571
−0.400
7.76E−07
3.69E−04

Tnfsf11
4
0.424
0.253
0.445
8.09E−07
3.83E−04

Rsrp1
4
0.414
0.551
−0.470
8.58E−07
4.04E−04

Cdk11b
4
0.149
0.284
−0.771
9.01E−07
4.22E−04

P2ry10
4
0.262
0.392
−0.583
1.12E−06
5.15E−04

Odc1
4
0.566
0.652
−0.516
1.53E−06
6.77E−04

Zfp36l2
4
0.419
0.279
0.651
1.53E−06
6.77E−04

BC031181
4
0.409
0.533
−0.477
1.90E−06
8.21E−04

Birc3
4
0.262
0.411
−0.586
2.37E−06
9.98E−04

Tgoln1
4
0.211
0.341
−0.597
2.82E−06
1.16E−03

Ccdc71l
4
0.144
0.267
−0.784
3.29E−06
1.32E−03

Rora
4
0.625
0.721
−0.327
3.67E−06
1.45E−03

Isy1
4
0.229
0.382
−0.531
3.74E−06
1.47E−03

Ubald2
4
0.219
0.364
−0.679
4.20E−06
1.64E−03

DIl1
4
0.059
0.153
−1.050
4.61E−06
1.79E−03

Dph3
4
0.203
0.345
−0.586
4.80E−06
1.86E−03

Rel
4
0.085
0.176
−0.907
5.09E−06
1.95E−03

Zfp36l1
4
0.913
0.848
0.290
5.89E−06
2.23E−03

Cited2
4
0.38
0.516
−0.524
5.89E−06
2.23E−03

Egr1
4
0.419
0.274
0.472
6.47E−06
2.42E−03

Eif4a1
4
0.694
0.749
−0.248
6.77E−06
2.52E−03

Gem
4
0.753
0.815
−0.384
7.89E−06
2.89E−03

Dusp5
4
0.36
0.505
−0.399
8.25E−06
3.00E−03

Serp1
4
0.445
0.566
−0.379
8.38E−06
3.04E−03

Herpud1
4
0.229
0.366
−0.605
8.85E−06
3.19E−03

Arf6
4
0.53
0.375
0.442
9.80E−06
3.50E−03

Ccnl1
4
0.285
0.409
−0.529
1.02E−05
3.61E−03

Nfkbiz
4
0.267
0.401
−0.538
1.04E−05
3.69E−03

Kdm6b
4
0.398
0.561
−0.392
1.04E−05
3.69E−03

Txk
4
0.324
0.441
−0.489
1.05E−05
3.73E−03

Eprs
4
0.141
0.26
−0.700
1.19E−05
4.13E−03

Dnajb2
4
0.069
0.166
−0.778
1.44E−05
4.93E−03

H2-K1
4
0.835
0.862
−0.192
1.49E−05
5.05E−03

Cisd2
4
0.229
0.354
−0.517
1.49E−05
5.06E−03

Nfkbie
4
0.159
0.239
−0.658
1.73E−05
5.76E−03

Snx18
4
0.129
0.246
−0.657
1.77E−05
5.88E−03

Ubald1
4
0.111
0.226
−0.735
1.79E−05
5.93E−03

Ramp3
4
0.201
0.329
−0.598
1.91E−05
6.27E−03

Nfil3
4
0.09
0.188
−0.714
2.40E−05
7.64E−03

Srsf5
4
0.697
0.774
−0.284
2.47E−05
7.82E−03

Icos
4
0.113
0.225
−0.789
2.60E−05
8.17E−03

Nr4a3
4
0.272
0.169
0.743
3.17E−05
9.73E−03

Slc3a2
4
0.404
0.348
0.374
3.38E−05
1.03E−02

Cdc14a
4
0.188
0.307
−0.494
3.76E−05
1.13E−02

Skil
4
0.247
0.376
−0.507
3.88E−05
1.16E−02

Klf2
4
0.388
0.423
0.325
3.94E−05
1.18E−02

Igha
4
0.964
0.963
0.253
4.00E−05
1.19E−02

Tpm4
4
0.332
0.465
−0.421
4.18E−05
1.24E−02

H2-Q4
4
0.17
0.282
−0.538
4.29E−05
1.27E−02

Naca
4
0.859
0.782
0.210
4.60E−05
1.35E−02

Arpc5l
4
0.221
0.105
0.710
5.25E−05
1.50E−02

Npc2
4
0.44
0.315
0.459
6.46E−05
1.80E−02

Arpc3
4
0.602
0.714
−0.251
6.62E−05
1.84E−02

Pcf11
4
0.067
0.153
−0.884
6.67E−05
1.85E−02

Lcp1
4
0.62
0.54
0.343
6.96E−05
1.92E−02

Gimap6
4
0.53
0.392
0.399
7.00E−05
1.93E−02

Sub1
4
0.823
0.848
−0.221
7.87E−05
2.13E−02

Pla2g16
4
0.254
0.138
0.633
8.15E−05
2.19E−02

Actb
4
0.964
0.934
0.449
8.19E−05
2.20E−02

Arih1
4
0.105
0.207
−0.641
8.87E−05
2.35E−02

Il22
4
0.252
0.378
−0.485
8.97E−05
2.38E−02

Ndufa8
4
0.373
0.251
0.299
9.70E−05
2.53E−02

Dad1
4
0.635
0.718
−0.325
9.83E−05
2.57E−02

Rinl
4
0.257
0.153
0.589
1.07E−04
2.76E−02

Clcn3
4
0.26
0.385
−0.467
1.16E−04
2.96E−02

D8Ertd738e
4
0.586
0.671
−0.294
1.24E−04
3.14E−02

Dok1
4
0.239
0.122
0.629
1.27E−04
3.20E−02

Opa3
4
0.077
0.164
−0.810
1.33E−04
3.33E−02

Dnajb9
4
0.157
0.254
−0.601
1.34E−04
3.36E−02

Dnaja2
4
0.267
0.153
0.596
1.35E−04
3.37E−02

Ffar2
4
0.437
0.315
0.472
1.36E−04
3.38E−02

Tmem59
4
0.707
0.571
0.166
1.46E−04
3.58E−02

Sdhaf1
4
0.362
0.226
0.490
1.50E−04
3.67E−02

Avpi1
4
0.18
0.272
−0.679
1.57E−04
3.80E−02

Tuba4a
4
0.1
0.192
−0.704
1.59E−04
3.84E−02

Traf1
4
0.432
0.537
−0.366
1.78E−04
4.23E−02

Dnajb6
4
0.306
0.383
−0.357
2.12E−04
4.92E−02

Ccl7
40
0.482
0.085
3.479
1.71E−08
1.14E−05

Ier2
40
0.643
0.271
1.132
2.10E−05
6.82E−03

Lat
42
0.7
0.556
−0.552
2.84E−05
8.83E−03

Atp5c1
42
0.7
0.111
1.086
1.39E−04
3.44E−02

Zfp36l1
42
0.2
0.778
−0.292
2.14E−04
4.95E−02

Agpat5
5
0
0.438
−4.897
1.57E−04
3.80E−02

Mgat2
5
0
0.562
−5.227
2.14E−04
4.94E−02

Jun
6
0.666
0.338
1.583
5.37E−85
3.47E−80

Zfp36l2
6
0.719
0.485
0.974
3.81E−52
5.83E−48

Fos
6
0.812
0.724
0.888
1.26E−49
1.88E−45

Neat1
6
0.778
0.712
0.716
2.00E−49
2.91E−45

Irf7
6
0.4
0.709
−1.088
1.22E−48
1.65E−44

Ppia
6
0.993
0.982
0.247
1.69E−35
1.18E−31

Btg1
6
0.965
0.987
−0.414
8.69E−33
5.32E−29

Rgs1
6
0.38
0.159
1.314
8.93E−33
5.41E−29

Zfp36
6
0.765
0.682
0.586
4.85E−27
2.12E−23

Ighm
6
0.948
0.976
−0.299
4.43E−25
1.68E−21

Ly6c1
6
0.938
0.947
−0.406
9.16E−24
3.12E−20

Klf6
6
0.442
0.284
0.903
1.27E−23
4.25E−20

Tsc22d3
6
0.592
0.448
0.555
7.80E−22
2.24E−18

Klf2
6
0.681
0.661
0.739
1.16E−21
3.28E−18

Ifi27l2a
6
0.625
0.805
−0.683
4.66E−21
1.29E−17

Cxcr4
6
0.447
0.272
0.755
1.66E−20
4.41E−17

Ly6c2
6
0.97
0.984
−0.405
3.35E−20
8.66E−17

Ddit4
6
0.188
0.055
1.655
1.08E−19
2.66E−16

Hist1h1c
6
0.324
0.184
1.030
2.84E−19
6.80E−16

Iglc1
6
0.309
0.57
−0.411
8.99E−19
2.03E−15

Jund
6
0.95
0.949
0.470
1.58E−17
3.13E−14

Fth1
6
1
1
−0.285
7.02E−14
9.75E−11

D13Ertd608e
6
0.654
0.585
0.320
7.46E−14
1.03E−10

Traf4
6
0.361
0.594
−0.613
8.63E−14
1.19E−10

Rpn2
6
0.486
0.395
0.495
1.04E−13
1.41E−10

Klk1
6
0.904
0.885
0.304
1.12E−13
1.51E−10

Psap
6
0.995
0.985
0.159
5.12E−13
6.43E−10

Evi2a
6
0.57
0.722
−0.349
1.57E−12
1.90E−09

Dusp1
6
0.382
0.262
0.853
2.33E−12
2.75E−09

Fyn
6
0.661
0.756
−0.315
4.81E−12
5.44E−09

Arpc2
6
0.874
0.928
−0.235
9.26E−12
1.01E−08

Ccl4
6
0.849
0.883
0.430
1.13E−11
1.22E−08

Trp53i11
6
0.232
0.436
−0.700
2.70E−11
2.82E−08

Runx3
6
0.424
0.621
−0.562
5.41E−11
5.42E−08

Ctsl
6
0.835
0.787
0.176
1.09E−10
1.04E−07

Tmem229b
6
0.43
0.605
−0.472
1.18E−10
1.12E−07

Pim1
6
0.282
0.506
−0.542
1.22E−10
1.16E−07

Hspa8
6
0.946
0.932
0.171
1.42E−10
1.35E−07

Cd69
6
0.471
0.373
0.538
1.47E−10
1.38E−07

Ubb
6
0.985
0.968
0.172
1.48E−10
1.39E−07

Rhob
6
0.19
0.113
0.790
1.60E−10
1.50E−07

Csrnp1
6
0.187
0.369
−0.676
1.70E−10
1.59E−07

Orai1
6
0.151
0.342
−0.812
2.91E−10
2.63E−07

Ifi44l
6
0.069
0.19
−0.991
3.23E−10
2.89E−07

Ifi44
6
0.087
0.213
−0.834
3.33E−10
2.97E−07

Ywhah
6
0.471
0.385
0.552
5.01E−10
4.34E−07

Igkv1-135
6
0.035
0.195
−1.520
6.19E−10
5.27E−07

Pltp
6
0.65
0.603
0.235
1.02E−09
8.42E−07

Cd7
6
0.892
0.944
−0.229
1.25E−09
1.01E−06

Tagln2
6
0.901
0.869
0.179
1.93E−09
1.51E−06

Vps37b
6
0.218
0.434
−0.767
2.91E−09
2.20E−06

Cdkn1a
6
0.071
0.186
−1.202
5.78E−09
4.13E−06

Bcl2l11
6
0.208
0.416
−0.809
9.18E−09
6.32E−06

Nfil3
6
0.076
0.22
−1.017
1.01E−08
6.88E−06

Adh5
6
0.232
0.169
0.390
1.93E−08
1.27E−05

Atp5c1
6
0.778
0.711
0.220
2.02E−08
1.32E−05

Arpc1b
6
0.919
0.944
−0.187
2.28E−08
1.47E−05

Cd37
6
0.649
0.597
0.256
2.90E−08
1.84E−05

Litaf
6
0.543
0.651
−0.348
3.37E−08
2.11E−05

H2-D1
6
0.916
0.957
−0.222
3.39E−08
2.12E−05

Irf2bp2
6
0.582
0.477
0.313
3.57E−08
2.22E−05

Gapdh
6
0.645
0.627
0.154
6.22E−08
3.67E−05

Pmepa1
6
0.163
0.303
−0.703
7.88E−08
4.56E−05

Clec10a
6
0.378
0.313
0.391
2.31E−07
1.23E−04

Insig1
6
0.297
0.447
−0.375
3.16E−07
1.64E−04

Srsf5
6
0.802
0.86
−0.323
3.48E−07
1.78E−04

Btg2
6
0.526
0.697
−0.306
3.82E−07
1.95E−04

Gapt
6
0.397
0.553
−0.390
4.28E−07
2.16E−04

Calm1
6
0.85
0.916
−0.186
5.39E−07
2.67E−04

Stat3
6
0.264
0.458
−0.611
5.43E−07
2.69E−04

Ly6e
6
0.615
0.736
−0.388
5.55E−07
2.74E−04

Ctbp1
6
0.486
0.63
−0.297
6.38E−07
3.10E−04

Ptprcap
6
0.768
0.724
0.170
6.73E−07
3.26E−04

Napsa
6
0.617
0.59
0.229
6.76E−07
3.26E−04

Eif4a2
6
0.635
0.572
0.262
7.76E−07
3.69E−04

Igkc
6
1
0.998
−0.201
8.90E−07
4.17E−04

Ier5
6
0.805
0.794
0.219
9.26E−07
4.33E−04

Csf2rb
6
0.296
0.46
−0.553
1.10E−06
5.07E−04

Ube2d2a
6
0.534
0.673
−0.304
1.30E−06
5.87E−04

Eif3i
6
0.472
0.426
0.223
1.31E−06
5.92E−04

Ube2d3
6
0.724
0.825
−0.202
1.34E−06
6.02E−04

Arid5a
6
0.328
0.494
−0.472
1.49E−06
6.62E−04

Ptpre
6
0.232
0.402
−0.567
1.58E−06
7.00E−04

Ablim1
6
0.166
0.335
−0.751
1.95E−06
8.37E−04

Prdx2
6
0.257
0.195
0.424
1.95E−06
8.37E−04

Spib
6
0.659
0.74
−0.270
1.96E−06
8.40E−04

Klk1b27
6
0.892
0.866
0.152
2.01E−06
8.61E−04

Cope
6
0.624
0.562
0.269
2.65E−06
1.10E−03

Cbfa2t3
6
0.18
0.314
−0.651
2.90E−06
1.19E−03

Sub1
6
0.95
0.965
−0.153
2.94E−06
1.20E−03

Myl6
6
0.812
0.786
0.172
3.10E−06
1.26E−03

Cct7
6
0.447
0.386
0.273
3.41E−06
1.37E−03

Sla2
6
0.59
0.525
0.287
3.45E−06
1.38E−03

Atf4
6
0.311
0.494
−0.601
3.66E−06
1.45E−03

S100a6
6
0.617
0.762
−0.324
4.09E−06
1.60E−03

Ctsd
6
0.361
0.299
0.336
4.33E−06
1.68E−03

Ptpn1
6
0.466
0.641
−0.390
4.98E−06
1.92E−03

Tmem251
6
0.158
0.284
−0.547
5.24E−06
2.01E−03

Gnas
6
0.951
0.972
−0.216
5.32E−06
2.03E−03

Batf
6
0.153
0.312
−0.708
5.59E−06
2.12E−03

Kmt2e
6
0.351
0.497
−0.416
6.45E−06
2.42E−03

Sepw1
6
0.776
0.855
−0.216
7.12E−06
2.64E−03

Cd8a
6
0.255
0.191
0.381
7.22E−06
2.67E−03

Cd48
6
0.444
0.431
0.240
1.06E−05
3.74E−03

Me2
6
0.21
0.357
−0.468
1.18E−05
4.13E−03

Hsp90aa1
6
0.479
0.506
0.175
1.38E−05
4.72E−03

Fam46c
6
0.139
0.287
−0.730
1.57E−05
5.32E−03

Kmo
6
0.551
0.658
−0.233
1.62E−05
5.44E−03

Sla
6
0.313
0.26
0.413
1.62E−05
5.46E−03

Asph
6
0.198
0.331
−0.557
1.84E−05
6.08E−03

Nrros
6
0.195
0.336
−0.536
2.11E−05
6.87E−03

Crem
6
0.22
0.389
−0.664
2.16E−05
6.98E−03

Ppp1cc
6
0.477
0.612
−0.237
2.26E−05
7.24E−03

Tmem59
6
0.65
0.585
0.239
2.55E−05
8.06E−03

Csnk2b
6
0.405
0.37
0.220
3.23E−05
9.87E−03

Hhex
6
0.358
0.301
0.200
3.50E−05
1.06E−02

Cnn2
6
0.44
0.381
0.284
3.56E−05
1.08E−02

Cdc42se2
6
0.314
0.466
−0.423
3.63E−05
1.10E−02

Hmgb2
6
0.356
0.375
0.286
3.67E−05
1.11E−02

Slc15a3
6
0.133
0.246
−0.605
4.98E−05
1.44E−02

Eif3d
6
0.336
0.284
0.318
5.06E−05
1.46E−02

Rnf149
6
0.365
0.493
−0.419
5.17E−05
1.49E−02

Clec12a
6
0.8
0.783
0.164
5.72E−05
1.63E−02

Aldoa
6
0.539
0.502
0.274
6.04E−05
1.70E−02

Cxxc5
6
0.373
0.508
−0.279
6.11E−05
1.72E−02

Mndal
6
0.36
0.467
−0.366
6.25E−05
1.75E−02

Polr3gl
6
0.333
0.481
−0.372
7.10E−05
1.95E−02

Pafah1b1
6
0.282
0.424
−0.322
7.38E−05
2.02E−02

Rsrp1
6
0.508
0.638
−0.235
8.19E−05
2.20E−02

Cdv3
6
0.292
0.428
−0.426
8.32E−05
2.23E−02

Ppp1r2
6
0.146
0.27
−0.566
8.41E−05
2.25E−02

Fcrla
6
0.617
0.599
0.212
8.57E−05
2.28E−02

Plekho2
6
0.096
0.221
−0.682
9.24E−05
2.43E−02

Mdh2
6
0.56
0.508
0.212
9.63E−05
2.52E−02

Tmem108
6
0.166
0.304
−0.730
1.01E−04
2.62E−02

Stat1
6
0.203
0.331
−0.414
1.02E−04
2.64E−02

Snx18
6
0.529
0.676
−0.354
1.05E−04
2.73E−02

Sh3glb1
6
0.371
0.541
−0.388
1.07E−04
2.75E−02

Blnk
6
0.61
0.715
−0.297
1.08E−04
2.79E−02

Rbm5
6
0.203
0.332
−0.496
1.09E−04
2.80E−02

Jakmip1
6
0.187
0.339
−0.505
1.12E−04
2.87E−02

Ppp2ca
6
0.461
0.573
−0.283
1.16E−04
2.96E−02

Kpna4
6
0.239
0.184
0.355
1.23E−04
3.12E−02

Pkib
6
0.566
0.692
−0.235
1.28E−04
3.22E−02

Ndufa13
6
0.738
0.703
0.169
1.30E−04
3.26E−02

Iqgap1
6
0.439
0.57
−0.347
1.35E−04
3.36E−02

Itpkb
6
0.146
0.266
−0.621
1.35E−04
3.37E−02

Cyth4
6
0.545
0.674
−0.190
1.45E−04
3.56E−02

Wnk1
6
0.334
0.504
−0.543
1.55E−04
3.76E−02

Npm3
6
0.403
0.366
0.213
1.55E−04
3.77E−02

Mef2a
6
0.331
0.394
−0.217
1.55E−04
3.77E−02

Fam117a
6
0.136
0.209
−0.376
1.62E−04
3.90E−02

Ubl3
6
0.412
0.561
−0.334
1.68E−04
4.03E−02

Gsn
6
0.622
0.587
0.184
1.73E−04
4.14E−02

Bri3
6
0.41
0.558
−0.335
1.83E−04
4.33E−02

Chrac1
6
0.198
0.32
−0.486
2.15E−04
4.96E−02

Ighg1
7
0.407
0
5.050
3.59E−18
7.66E−15

Gm2a
7
0.642
0.398
1.626
5.92E−12
6.60E−09

Actb
7
0.992
0.971
0.962
3.97E−11
4.06E−08

Il17rb
7
0.293
0.019
3.210
2.95E−10
2.66E−07

Smco4
7
0.659
0.32
1.788
5.54E−10
4.77E−07

Gata3
7
0.618
0.388
1.226
2.27E−09
1.76E−06

Igkv1-135
7
0.016
0.252
−2.815
2.39E−09
1.84E−06

Igha
7
0.992
0.99
0.455
3.88E−09
2.84E−06

Gimap4
7
0.439
0.738
−0.828
7.29E−09
5.13E−06

Jun
7
0.569
0.194
1.121
1.42E−08
9.54E−06

Dusp5
7
0.341
0.68
−0.905
1.95E−08
1.28E−05

Fgl2
7
0.455
0.194
1.771
3.97E−08
2.44E−05

Mcpt1
7
0.195
0
4.373
4.26E−08
2.60E−05

Vps37b
7
0.39
0.728
−0.964
5.97E−08
3.54E−05

Ddit4
7
0.366
0.107
2.414
7.06E−08
4.12E−05

Ubald2
7
0.325
0.65
−0.844
9.80E−08
5.56E−05

Lgmn
7
0.35
0.078
2.276
1.05E−07
5.97E−05

1700061F12Rik
7
0.244
0.019
3.537
2.06E−07
1.11E−04

Ifngr1
7
0.496
0.757
−0.885
6.29E−07
3.06E−04

Cst7
7
0.463
0.136
1.346
6.44E−07
3.13E−04

Il4
7
0.317
0.068
2.197
9.09E−07
4.26E−04

Zeb2
7
0.203
0.01
3.094
2.54E−06
1.06E−03

Igkc
7
1
1
0.756
3.05E−06
1.23E−03

Ccl5
7
0.114
0.34
−1.521
7.96E−06
2.91E−03

Ltb
7
0.463
0.777
−0.502
8.51E−06
3.08E−03

Pik3r1
7
0.374
0.67
−0.770
1.32E−05
4.56E−03

Foxp3
7
0.138
0.369
−1.433
3.47E−05
1.05E−02

Il21r
7
0.13
0.379
−0.811
4.26E−05
1.26E−02

Foxp1
7
0.431
0.223
1.129
4.28E−05
1.26E−02

Dusp1
7
0.87
0.709
0.631
4.64E−05
1.36E−02

Tmsb4x
7
1
1
0.377
6.83E−05
1.89E−02

Got1
7
0.171
0.379
−1.199
8.56E−05
2.28E−02

Pxdc1
7
0.154
0.01
3.051
9.85E−05
2.57E−02

Fas1
7
0.033
0.184
−1.603
1.07E−04
2.75E−02

Cd27
7
0.48
0.563
−0.759
1.17E−04
2.97E−02

Txk
7
0.065
0.252
−1.234
1.52E−04
3.70E−02

Tmsb10
7
0.976
1
−0.179
1.56E−04
3.78E−02

Gzma
7
0.317
0.117
1.230
1.57E−04
3.79E−02

Pim1
7
0.52
0.728
−0.660
1.98E−04
4.63E−02

Icos
7
0.488
0.738
−0.538
2.09E−04
4.84E−02

Ikzf2
8
0.099
0.26
−1.020
1.37E−07
7.61E−05

Ubald2
8
0.464
0.644
−0.714
2.09E−07
1.12E−04

Ppp1r15a
8
0.304
0.575
−0.642
4.53E−07
2.28E−04

Litaf
8
0.326
0.582
−0.663
2.58E−06
1.07E−03

Gimap7
8
0.519
0.247
0.937
1.08E−05
3.81E−03

Orai1
8
0.127
0.349
−1.213
1.29E−05
4.46E−03

Zc3h12a
8
0.077
0.288
−1.472
1.31E−05
4.52E−03

Dusp2
8
0.613
0.404
0.686
2.44E−05
7.76E−03

Prr7
8
0.066
0.24
−1.385
2.58E−05
8.13E−03

Btg1
8
0.912
0.973
−0.402
3.21E−05
9.84E−03

Irf7
8
0.138
0.322
−1.262
3.96E−05
1.18E−02

Zfp36
8
0.376
0.144
1.132
5.81E−05
1.65E−02

Tob2
8
0.11
0.253
−1.231
5.81E−05
1.65E−02

Rgs1
8
0.691
0.486
0.864
9.21E−05
2.42E−02

VgIl4
8
0.331
0.555
−0.657
1.07E−04
2.75E−02

Sh2d1a
8
0.431
0.247
0.847
1.22E−04
3.10E−02

Igkc
8
1
1
0.307
1.27E−04
3.20E−02

Jun
8
0.343
0.151
1.129
1.32E−04
3.32E−02

Vps37b
8
0.702
0.836
−0.490
1.33E−04
3.33E−02

Ctla2a
8
0.464
0.425
0.531
1.35E−04
3.37E−02

Nr4a2
8
0.265
0.493
−0.758
1.36E−04
3.38E−02

Pim1
8
0.63
0.815
−0.376
1.53E−04
3.73E−02

Sptssa
8
0.42
0.199
0.904
1.71E−04
4.09E−02

Ifrd1
8
0.232
0.425
−0.686
1.80E−04
4.27E−02

4930523C07Rik
8
0.215
0.425
−0.724
1.83E−04
4.33E−02

H2-D1
8
1
0.993
−0.212
2.09E−04
4.84E−02

Al504432
9
0.057
0.636
−2.126
4.42E−05
1.30E−02

TABLE 4

A-K. Top 50 genes in each topics revealed by topic modeling on T cells, B cells,

DCs, myeloid cells and stromal cells in PP and LP regions, related to FIG. 3.

A. T cells LP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7
topic_8

mt-Co1
Eef1a1
Igfbp4
Gimap5
1700061F12Rik
H3f3b
Malat1
Actb

mt-Atp6
Gm8730
Dapl1
Gabarap
Il13
Ier2
Zfp369
Pdcd4

Gmfg
Gm10260
Ccr7
Rbck1
Scin
Junb
Gtdc1
Cbx3

Myl12b
Eef2
Pdlim4
Cops4
Lgmn
Tnfaip3
Dusp23
Abhd2

Sfxn2
Gm10709
Lef1
mt-Nd1
Hlf
Pim1
5330439K02Rik
Ccdc38

Socs3
Fau
Bcl2
Bcl7c
Smco4
Ppp1r15a
5430421N21Rik
Tnfrsf19

Cd53
Naca
Sell
Iqgap1
Npnt
Dusp5
Ltk
Ncoa3

Acp5
Eif3k
Ifngr2
Ralbp1
Il17rb
Crem
Mdm4
Il17f

Gm12840
Eif3f
Gm8369
Ier3ip1
Deptor
Atf4
Snapc3
Ptpn22

Mbp
Pabpc1
Satb1
Dock10
Gata3
Ramp3
Gm28424
Trav3-1

Rasal3
Btf3
Gm9889
0610030E20Rik
Gm2a
Nfkbia
Gm16894
Sv2a

Atxn7l1
Tmsb10
Smc6
Ptbp1
Il6
Jund
Stk3
Fxyd4

mt-Nd2
Wdr89
Hotairm1
Emp1
Il17a
Nr4a1
Klhl4
Lta

Gltscr2
Cct4
Khdrbs3
Scand1
Ltb4r1
Tgif1
Serinc2
Ankrd23

Ets1
Kif1b
Actn1
Zfp672
Fgl2
Pnrc1
Herc2
Alkbh5

Son
Bola2
Ms4a4b
Lrmp
Areg
Ier5
Apc
Bend5

Kcnn4
Pelp1
Rapgef4
Usp9x
Fbxl21
Eif1
Pgap3
Ptp4a2

Uqcrfs1
Eef1b2
Amigo2
Gm10814
AA467197
Nr4a3
P4htm
Nthl1

Cd3d
Dkc1
Atp1b1
mt-Nd3
Il1rl1
Zfp36
Ptpre
Caprin2

Lrp12
Mrps33
Eml5
Emd
Mel
Sub1
Tnrc6a
Zfp763

Casp8
Gm10073
Sh3bp5
Sipa1
Gm5544
Calm2
Map1b
Tctn1

Gypc
Gm2000
Trav17
Dnajc14
Tmem159
Dnajb6
Antxr2
Gga2

Ap5b1
Nhp2l1
Btg1
Trappc4
Rasgrp4
Ifrd1
Trbv19
Armcx6

Tes
Gnb2l1
F2rl1
Akap13
1700012B07Rik
Zc3h12a
Uhrf2
Sostdc1

Trim26
Eif6
Gm11808
Desi1
1700113H08Rik
Traf1
Aagab
Gm43625

Arid5a
Gm9493
St8sia6
Srebf2
St6galnac5
Srsf2
Cr1l
Fcer2a

Abcb9
Rexo2
S1pr1
Gngt2
Il4
Tgif2
Ei24
Carm1

Stk17b
Gm6133
Klhdc2
Uqcrb
Chdh
Kras
Gm17518
Nrg4

Snrpd3
Atp1a1
Foxp1
Sppl3
Slco2b1
Klf2
Lix1l
Tlr7

Hmha1
Klrb1a
Npc2
Tmem167
Ccr9
Rnf125
Dmrta1
Tmem121

Rragd
Sepw1
Saraf
Ssbp2
Epas1
Bud31
Uchl4
Slc39a1

Wnk1
Emc6
2610020C07Rik
Sec61g
Grp
Il2rg
Sgtb
Gm42809

Arhgap15
Prorsd1
Myo19
Manbal
Lztfl1
Cd69
Nfam1
Fitm2

Siah1a
Ndufa6
Ranbp6
Fkbp3
Gm10369
Csrnp1
Ackr3
Dqx1

Tcf25
Nhp2
Cmah
Fis1
Kif19a
Apoe
Arhgef9
Clec10a

Wdr33
Gm9843
Treml2
Kdm2b
Tenm4
Cep85
Ighv1-64
Ankrd60

Cbx4
Yeats4
Drc1
Fip1l1
Serpinf1
Coq10b
Trav9-2
Gm14154

RP23-428N8.3
Gm26545
Prrg1
H2afv
Gnb2
Gpr132
Gm3716
Upf1

Gna1
Ctdsp1
Usp28
H2-Q10
Ubox5
Cd209b
Evx1
Marf1

Clec2l
Eef1d
Atp1b3
Hdgfrp2
Plcl1
Pcna-ps2
Plxnb2
Actr2

Cd247
Rbfa
Rab3ip
Nsmce1
Rab31
Fus
Ascl3
Mapkbp1

Gltp
Pfdn5
Trib2
Fastk
Ffar2
Cap2
Gm8973
1110035H17Rik

Rock1
Eif5a
Rpusd2
Ndufb7
Slx1b
Ifnar1
Hhex
Eid2b

Eif3i
Atp5e
Il4ra
Ndufs4
Asb2
Nfkbie
Armt1
Kalrn

Ctss
Ndufa10
Il6ra
Prdx5
Zfp85
Ube2b
Ccdc86
P3h4

Ccm2
Cycs
Whsc1l1
Tbl1xr1
Tmsb4x
Dus2
Hbegf
Notch2

Zmat2
Ppp1r14b
Ggt1
Sf3b5
Hdc
Birc3
Stkld1
Mcpt1

Fxyd5
Tomm7
Prdx6
Tomm34
Pxdc1
Hnrnph1
Zswim3
Gskip

Bnip3l
Snrpf
Pygm
Bend4
Heatr1
Osgep
Edaradd
Dpysl2

Dnajc25
Cox7a2l
Itga6
Gng7
Lgals7
Igkv5-37
C030034L19Rik
Lsm14b

topic_9
topic_10
topic_11
topic_12
topic_13
topic_14
topic_15
topic_16

Tnfrsf4
Ube2c
Fos
Trpm1
Crip1
B2m
Cel5
Iglc2

Foxp3
Actg1
Hspa1a
Prss2
Ccr2
H2-K1
Nkg7
Igkc

Tnfrsf9
Lgals1
Rgs1
Gm26825
Emp3
Ubb
Klra7
Jchain

Cd83
Ccna2
Jun
Zfp266
Zfat
H2-D1
Gzmm
Igha

Ikzf2
Tuba1b
Klf6
Kifap3
Klf3
Gimap4
4930486L24Rik
Mzb1

Izumo1r
Hmgb2
Dnajb1
Mareks
Map4
Psme1
Cd200r2
Iglc1

Mmd
Tubb5
Hist1h3a
Igkv4-50
Plekha6
Gm28707
Gzma
Hsp90b1

Itgb8
Fam64a
Hsp90aa1
Acp2
Glipr2
Itpripl2
Xcl1
Pdia4

Penk
Mybl2
Gm29666
Ptpn23
Myl10
Polr1b
Cd8a
Txndc5

Ifi27l2a
Cfl1
Ampd2
Rpgrip1
Atrnl1
Isgl5
Cd7
Mef2c

Tnfrsf18
Birc5
Btg2
Gm17275
Zfp318
Siae
Klrd1
Creld2

Ctla4
Pttg1
Tiparp
Ccdc51
Ptpn18
Igtp
Cel3
Derl3

Rgs10
Stmn1
Pygl
Ppp1r12b
Recql5
Cul5
Ccl4
Cacna1e

Zfp36l1
Cenpk
Cops6
Klhl35
Dennd1a
Ighv1-80
Ppp2r2c
Arx

Nrip1
Slc30a2
Ppp1r3b
Sumf2
Gm26740
Gm14306
Zmat4
Ftx

Gpm6b
Cenpf
Gle1
Sh3pxd2a
Gm37696
Ifi35
Gzmk
Gm43121

S100a11
Actr3
Efna4
Dcaf13
Mboat4
Tbc1d31
Pdzk1
Fkbp2

Capg
Gapdh
Litaf
Arl11
Tnnt3
Tifab
Klrk1
Sdf2l1

Il10
Rad54l
Anks3
Cnr2
Ppp1r14a
Travl6n
Slc16a11
Edem1

Lag3
Eme1
Dtx4
Abcb6
Ift74
AW112010
Car2
Cd79a

Tiam1
Nek2
Tab2
C230037L18Rik
Klrb1b
Psmb10
Dact2
Iglv1

Matk
Ect2
Ahcyl1
Gm26910
Odf2l
Shisa5
Adrb1
Fkbp11

Wisp1
Cntnap2
1110001J03Rik
Oasl1
Arl6ip5
Xrcc2
Ablim2
Manf

Gas2l3
Bcam
Dusp1
Bin3
Il23r
Cyp26b1
Slc9a3r2
Slc7a11

Fgf16
H2afx
Fam103a1
Gtf2ird2
Ppplrl2a
Rarres2
Cited4
Rab25

Hist1h4c
2810417H13Rik
Nabp1
Dgcr8
Zfp40
Ighv14-2
Klra5
Mfsd2a

Ccl20
Ccnb2
A630001G21Rik
Anapc2
Thy1
Armc2
Serpinb6b
Rhd

Slc7a10
Rad51ap1
Fam189b
Gcfc2
Elf4
Dapk1
Lmo1
Pla2g5

Fam46a
Pfn1
Osgin1
Caleb
Lsp1
Zfp964
Tlr6
Ccdc18

Ptprcap
Esco2
Qpct
Gstt1
2010320M18Rik
Tapbp
Pdgfb
Bhlhal5

H1f0
Neil3
Myo7a
Pard3b
Adcy7
A730015C16Rik
RP24-330M21.1
Bcat1

Tbc1d4
Kif4
Susd4
Thnsl1
Csl
Cntd1
Rasgef1c
Arfgef3

Ankrd55
Arhgap19
Al847159
Gm14321
Ulk3
Zbp1
Emilin2
Gm867

Bcar3
Hist1h2ap
Evx1os
Eng
Mcm9
Krit1
A930011G23Rik
Fabp3-psl

Gm3488
Top2a
Adamts14
Gps1
Cpne4
Cacng8
Gm11491
Mettl21b

Nefm
Cks1b
Stac3
Ddr1
Spaca6
Egfl8
Ccdc14
Mcemp1

Alox8
Cotl1
Rhoq
Rasl11a
Abcc10
Gm8444
1810006J02Rik
Arhgef40

Celf5
Cdkn3
Nox1
Gm17089
Enpp2
Tinf2
Trgv2
Piwil2

Slc26a11
Rbm3
Wdr19
Eme2
Slc27a1
Mbnl3
Tcrg-C2
2010007H06Rik

Camk2n1
Myl12a
Sema7a
Gm12454
Lancl3
Gbp4
Tlr12
Plekhh3

Pdcd1
270094K13Rik
Anks6
Gm43740
Ighv1-15
Smpd1
Wdr95
Spata32

Zan
Kif18a
Gm17056
Mtus2
Ccne2
Rnf13
Itln1
Cyb561

Gm3739
Plk1
Lamtor2
Mdfi
Fbxl13
Psmb9
Ifng
Apoh

Gm3667
Lockd
Tgfbr1
Gm43691
Gm43153
Cyp4f18
3110082l17Rik
Arsg

Tnfsf8
Hist1h2ag
Gm10031
Zcchc24
Arg2
Mvk
1700021A07Rik
Mgat3

Maf
C330027C09Rik
Dapk3
Gm28731
Slco4a1
Mccc1
Nr4a2
Endou

Egln3
Trip13
Dnaja4
Lrrc27
Rab34
Stat1
Htra1
Gm20517

Gm3636
BC030867
5033417F24Rik
Zfp937
Gpr25
Got1
Gm27194
Pank1

Spock2
Sgol2a
Ehbp1
Coasy
Gm20750
Gbp2b
Cd8b1
Pbx1

Myo1h
4930524J08Rik
Serpinb1b
Slc9b2
Nos3
Myof
Klrc1
Phka1

B. B cells LP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7
topic_8

Igkc
Igha
Mzb1
Cd74
Jchain
Fos
Malat1
Crip1

Igkv6-23
Rec1l4
Hsp90b1
Tmsb4x
Ighg2c
mt-Nd1
Gm42418
Psma7

Ighv6-7
Igkv3-8
Sec61b
H2-Aa
Iglv1
Jun
Ccdc88a
Srsf6

Igkv8-27
Stab1
Ppib
H2-Eb1
Ly6c2
mt-Atp6
Gm26917
Dnaja2

Igkv12-41
Tmem147os
Sub1
H2-Ab1
Ly6c1
Jund
Txndc5
Nop56

Pomgnt2
Gm14327
Manf
Fau
Edem2
Fosb
Rbm39
Trp53il1

Slc1a1
4930451G09Rik
Calr
H2-DMb2
B2m
Nfkbia
Gm42726
Eif4g2

Ighv1-30
Ighv1-19-1
Pycard
Ebf1
Insl6
H3f3b
Zfp292
Hypk

AY074887
9530052E02Rik
Hspa5
H2-Ob
Procr
mt-Co3
Kmt2e
Cnbp

Igkv9-124
Gm14399
Pdia6
Fcer2a
Dmtn
mt-Cytb
Rrbp1
Ahsa1

Cbs
Gm26596
Ighg2b
Ighd
Selm
Dusp1
Krr1
Cox7b

Igkv17-127
Platr17
Sec61g
Cd79b
Iqcd
Dusp5
4930523C07Rik
Wbp11

Gm15104
Iqca
Pdia4
Ms4a1
Iglv3
Cacna1s
Creb3l2
Psmc5

Syce1
Myo3b
Dnajb11
4930597A21Rik
Ighv1-15
Ier2
Slc48a1
Ndufa5

Gm26527
Igkv9-123
H13
Pax5
Gm15284
mt-Co2
Zdhhc14
Mrpl21

Abca17
Ttyh1
Sdf2l1
Cxcr5
1700047l17Rik2
mt-Nd4
Ankhd1
Ociad1

Nsg2
Gnrh1
Tnfrsf17
Cd72
Sdc1
Ftl1
Upf2
Pfdn6

Gm17529
Fabp1
Krtcap2
Sapcd1
Copz2
Mt1
Nfkbil1
Arpc2

Spin4
Krt7
Ddost
H2-DMa
Gm20878
Ier5
Zmynd11
Mrpl40

Col5a3
Zfp174
Ssr2
Eef1a1
Ryr1
Ppp1r15a
Gm26719
Nsun2

A830009L08Rik
Cdh24
Ssr3
Cd22
Gpnmb
Cxci10
Cyld
Ubtf

Cps1
Gm26515
Reep5
Ly86
Pycr1
mt-Co1
A630072M18Rik
Cmtm7

Clec4a4
Rhobtb3
Lman1
H2-Oa
Cst6
Rilpl2
Rbm26
Rrp1

Col4a2
Gm15445
Rpn1
Cox7a2l
Igfn1
Pnrc1
Nek7
Morf4l1

Prox2os
Mdfi
Emp3
Eif3f
Cdnf
Ubald2
Cspp1
Ndufb5

Pdc
Cfap53
Pdia3
1-Mar
Bhlha15
Lmna
Map3k10
Tomm22

1700019B03Rik
Tal2
Srp9
Eef2
Ighv1-23
Hes1
Zfp51
Ndufa7

Ighv1-61
Zp3
Fkbp11
Rac2
Vps37d
Herpud1
Mvp
Pcnp

Lcat
Nr3c2
Spcs2
Ccr7
Akap6
Egr1
2510039018Rik
Gars

Igkv8-16
Rdh1
Spcs1
Fcmr
Igkv1-110
Ly6d
Map3k1
Basp1

Ripk4
Tmem202
Ift20
Spib
Extl1
Serp1
Ppt1
Pafah1b3

D930048G16Rik
Gm43616
Ostc
Dusp2
Ckmt1
Cd69
Vwa1
Mrpl11

RP23-138J20.8
Frzb
Sec11c
Rapgef4
Ero1lb
mt-Nd3
Rabac1
Srrm1

Sec31b
Kcna2
Cope
Cotl1
Fam71b
Mt2
Alyref2
Csnk2b

Gm20632
Gm37027
Derl3
Gm9843
Ighv1-20
Rhob
Gm26586
Abcf1

Etv2
Padi3
Cd52
Siglecg
Gm20478
Xbp1
Ggnbp2
Caprin1

Gm17034
Aqp7
Rpn2
Coro1a
Gm5134
mt-Nd2
Slc16a6
Ddx21

Wisp2
Gm14453
Slc35b1
Pold4
Gm29375
Mel1
Nacc2
Serbp1

RP24-159C12.10
Dusp27
Ssr4
Bin1
Dlg2
Rgcc
Gigyf2
Mrps33

Tbx15
Slc6a12
Tmbim6
Bank1
Gpr31b
Zfp36l1
Clec2d
Mrfap1

Mlana
Scn2a1
Lman2
Cd37
Kcnmb4os2
Ode1
Arhgap22
H2afy

Synm
Hoxb1
Creld2
Gm43603
Ighv10-3
Clic4
Ankrd40
Eif1b

Gm26663
1700001L19Rik
Ccr10
Rgs13
Atp6v0e2
Txnip
Cped1
Cnot2

Gm43479
Pabpn1l
Atp5g1
Zfp318
Rnf123
Atf4
Fam214a
Oaz1

Gm12735
Dynlrb2
Srprb
Scd1
F420014N23Rik
Fam46c
St6ga1nac4
Pfn1

Gm19902
Mb21d2
Os9
Blk
Btd
Chac1
Ddx46
Dnajc8

Sema6c
Gm19345
Erp44
Cnn2
Gdap2
5031425E22Rik
Fam117a
Arf1

A530013C23Rik
Tmem253
Scpep1
4930426D05Rik
Nron
Klf2
Stk25
Mrpl54

Nav3
Gm42749
Kdelr1
Fth1
Gm26725
Hist1h2bc
RP24-172H24.1
Chchd10

Cacna1f
Sstr2
Srp72
Napsa
Gm12474
Ddit3
Tnfrsf13b
Eif3a

topic_9
topic_10
topic_11
topic_12
topic_13
topic_14
topic_15
topic_16

2810417H13Rik
Iglc1
Xist
Mcpt1
Ighg1
Iglc2
Slpi
Ighm

Birc5
Iglc3
Peli1
Lyz2
lgkv3-4
Igkv9-119
Actb
Phactr1

Stmn1
Pcsk5
Mef2c
Mcpt2
Pon3
Igkvl4-111
Igkv3-7
Igkv16-104

Hmgb2
Gm43409
Tcf4
Tyrobp
Cldn4
Iglv2
Ighv1-18
Ccdc155

Ptma
Mc1r
Arl2bp
Ighg3
Kcnh2
Iglc4
Stt3b
Nr6a1os

Tubb5
1700017D01Rik
Akap13
Ccl4
Nat8
Gm11444
Tsc22d3
Gm648

Ube2c
Lrrc46
Alkbh5
Ighv2-3
Hey2
Trav13-1
Sdc4
Smoc2

Tuba1b
Gm28198
Fli1
Gzma
Gm14210
Gm28513
Gprl71
Fhad1

Nusap1
Sst
Ctbp1
Cpa3
Kcnq4
Cacna2d1
lghv1-21
Gm26840

Hist1h2ap
Igll1
Tmem57
Psap
Gm29395
Mettl21c
Cited2
1700061G19Rik

H2afz
Tnr
Vgll4
Ccl5
Hist1h1t
Trbv14
Gm37511
Stkld1

Cenpf
Tenm3
Hmgn3
Plac8
Nmur1
BC049352
Kdelr2
Asb18

Rrm2
Slc38a5
Dennd4a
Trbc2
Pip5kl1
Prom1
Ywhaq
Gm26646

Cdkn3
Gm20468
Igkv12-46
Maf
Atp6v1g3
Necab3
Pole2
Gm43569

Ccnb1
Angptl7
Insig1
Cma1
D930007J09Rik
lgkv1-99
Tram1
Gm15819

Ube2s
Gm10719
Tgoln1
Il1b
Fbxo24
Gm17151
Vpreb3
Fmo2

Ccna2
Pcdh19
Psd4
Ifitm1
Plxnb1
Gm43734
Rbm47
Lrrc74b

Cenpe
Hpca
Marf1
Id2
Gm28551
Gm44175
Pitpnc1
Fer1l6

Ran
Plvap
Ddx3x
1700061F12Rik
Trim66
Pappa
Lgals1
Ncs1

Uhrf1
Gm26681
Hmg20b
AW112010
Drp2
2610528Jl1Rik
Atp6v1g1
Pdilt

Cep55
Gnao1
Skil
Cxcl2
Gm16494
4930481A15Rik
Naa38
Casq1

Top2a
Gja5
Bcl21l1
Apoe
Gdap1l1
Eci3
Dap
Ly6k

Kif22
Klkb1
Cnppd1
Ifitm2
RP23-53O7.2
Muc2
Slc39a1
Gm26780

Cdc20
Gm19434
C87436
Mpeg1
Boll
D630029K05Rik
Entpd7
Gm14137

Plk1
Fgf16
Slc25a36
Trbc1
Tsx
Gfra2
Zbtb20
Cpq

Cdc45
Ccdc96
Mdm4
Cd7
Gm16982
Gm15356
Tox
Tmbim7

H2afx
D7Ertd443e
Wnk1
Cox6a2
Apol6
Rlbp1
Gm19585
lgkv4-57

Cdca3
D030040B21Rik
Ccm2
Mcpt9
Gm42957
Gm10516
Upf1
Igkv2-112

Mcm5
Tmcc2
Prkcd
Furin
Irx5
Smkr-ps
Timmdc1
Slc7a7

Cdca8
Al661453
Elf1
Kdm6b
lgkv4-63
Mfsd7c
Eaf2
Gp2

Pbk
Gm44037
Tomm5
Il4
Iqch
Adamts12
Pycr2
9430069l07Rik

Ccnb2
Gm26550
Rbms2
Alox5ap
Slc27a2
Gm37240
Khdc1a
Csn3

Mybl2
Tmem45a2
Phf3
Igkv12-40
Apol8
Art3
Xlr4b
Zfp316

Nuf2
K230010J24Rik
1300002E11Rik
C1qc
Gm26883
Nlrp1b
Emc10
Mpp7

Hmmr
lghv3-4
Ubxn2a
Fcer1a
Shank2
Clca3b
Fkbp8
Gm43218

Cit
Cdhr1
Nktr
Lgals3
Ighv1-43
Rab33a
Yrdc
Igkv4-86

Pttg1
Ighv1-53
Slc38a2
Cd63
Igkv1-88
Pcdhb19
Kcnn4
Prg2

Spc24
Npm2
Bhlhe41
Siglech
Mx1
Gm42669
Arf4
Rab3b

Hmgn2
5730460C07Rik
Birc2
Actn2
1700023F06Rik
Defa-rs1
Dnajb9
3222401L13Rik

Esco2
Cebpe
Coa5
Itm2b
Abcc3
Pglyrp4
Per3
Myo5c

Cdk1
Vtn
Safb2
Igkv19-93
Klhl40
Flrt1
Tmem50a
Ccdc3

Ckap2l
Gm12666
Ddx50
Nkg7
Igkv8-18
Tpbg
Fn3krp
D630003M21Rik

Chaf1a
Rem2
Rbm25
Cxcr6
1700010K24Rik
Gm15895
Uqcrq
Tom1l1

Ybx1
Gm26765
Zfp787
Adamdec1
Samd3
3110070M22Rik
Pcca
Gm6034

Neil3
Gm15978
Ube2h
Gata3
A930006L05Rik
Cadps
Eif5b
Tspan32os

Smc4
lghv1-55
Alkbh1
Mcpt4
Klhl31
Necab1
Luc7l2
Stox2

Asf1b
RP23-366014.5
Raf1
Zfp36l2
Gm4787
5430402013Rik
Igkv12-38
C1ra

Cks2
BC043934
Ppcdc
Lair1
Gm12333
Mptx2
Tagln2
Sox12

Cks1b
Gm26707
Bcl7c
Ccl3
1700088E04Rik
AY761184
Tmem173
C2

Smc2
Gm19684
Dennd5b
Emb
Gzmk
Tc2n
Ccdc117
2610528A11Rik

C. DCs LP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6

Siglech
Ctla2b
Lyz2
Stmn1
Cd74
Ccl17

Cox6a2
Xcr1
Il22ra2
2810417H13Rik
H2-Ab1
Malat1

Klk1
Ppt1
Siglece
Ptma
H2-Aa
Ccl22

Cd8b1
Cst3
Plet1
Ube2c
H2-Eb1
Ftl1

D13Ertd608e
Naaa
S100a11
Hmgb2
Ifitm3
Ccr7

Sh3bgr
Tlr3
Cxcl14
Tuba1b
Wfdc17
Cxcl1

Pacsin1
A530099J19Rik
Mmp12
Birc5
Clec4b1
Flrt3

Ccl4
Hebp2
Gp2
Tubb5
Cd209a
Fscn1

Sell
Actg1
Ppplrl4a
Rrm2
H2-DMb1
Lad1

Ly6c2
Plpp1
B4galt6
Ccnb2
Ifitm2
Cacnb3

Lefty1
Ptgis
Vasp
Nusap1
H2-DMb2
Bcl2a1d

Smim5
Eef1b2
Atox1
Ran
Cd209b
Cdkn1a

Bst2
Cxx1a
Atp5e
Ccna2
Socs3
Ankrd33b

Tyrobp
2310031A07Rik
Fpr2
Cdca3
Srgn
Ccl5

Ly6cl
Atpif1
Sec61b
Ranbp1
Smpdl3a
Tmem123

Ighm
Vwf
Ifitm6
Ppia
H2-D1
Cxcl2

Cdh5
Ucp2
Sh3bgrl3
H2afx
Gadd45g
Cxcl16

Dnajc7
Txndc15
Msrb1
Cks1b
Hfe
Bcl2a1b

Ctsb
Cxx1b
Ccr1
Tk1
Trf
Arl5c

Dntt
Rundc3a
Tnni2
Top2a
Hcls1
Gadd45b

Gm14964
Acvrl1
Arpc1b
Anp32b
Gsn
Apol7c

Prkca
Psmb9
Mcemp1
Cep55
Cd53
Basp1

Lair1
Aif1
S100a6
Erh
Ms4a4c
Bcl2a1a

Atp2a1
Agpat3
Cyp4f18
Cdkn3
Atp6ap2
Il4i1

Ccr9
Cd207
Trem1
Ybx1
App
Etv3

Mctp2
Fam149a
Tctex1d2
Ckap2l
Bcap31
Cd83

Timp2
Psme1
Igsf6
Cenpe
Hexb
Serpinb9

Iglc3
1700009J07Rik
Lyz1
Ccnb1
Ms4a6d
Nudtl7

Klk1b27
Rab32
Il1rn
Alyref
Cysltr1
Traf1

Pir
Plbd1
Serf2
Hmgb1
Bicd2
Cxcl10

Nrxn2
Gm11837
Spi1
Ska1
Gm5150
Zmynd15

mt-Atp6
Ttc39a
Fam189a2
Tmpo
Itm2b
Tspan3

Tbxa2r
Rgs10
Tgfbi
Cdca8
Dab2
Samsn1

Grn
Tmsb4x
Adamdec1
Prc1
Csf2ra
Mt2

Dap
Cd52
Bcas1
H2afz
Susd3
Csrp1

Blnk
Rab7b
Cox4i1
Dut
Ebp
Lrrc32

Atp1b1
Cd36
Atp5l
Cenph
Milr1
Clic4

Clec12a
Qpct
Stra6l
Cdca7
Man2b1
Il12b

Gm5547
Lpar6
Clec4a4
Npm1
Itgam
Marcksl1

Gm12253
P3h2
Il23a
Mcm6
Slc44a5
Map4k4

Il12a
Proser2
Pald1
Prdx1
Ptger3
Mxd1

Scimp
Gm28411
Sirpa
Melk
Myl12a
Cd40

Rpgrip1
Col25a1
Myeov2
Snrpd1
Ppp1r13l
Tnnt2

Pgls
Sult1a1
Nedd8
Pttg1
Dmkn
Cdkn2b

Paqr5
Snx22
Atp6v1f
Cdk1
Mgl2
Rgs1

Fcrla
Cyp26bl
Tarm1
Nuf2
Ctsc
Lilr4b

Gm19705
Pmf1
Tsga10ip
Snrpb
Aph1c
Fam49a

Irf7
Kremen2
Clec5a
Hnrnpa3
Ticam1
Tnfaip2

Hpse
Gm6377
Cox6c
Bub1
AF251705
Eno3

Havcr1
Commd8
Calml4
Pfn1
Gm43936
Il1a

topic_7
topic_8
topic_9
topic_10
topic_11
topic_12

Junb
Actb
Fth1
Klf2
Igkc
S100a4

Btg2
Gm2a
Tpt1
Fos
Igha
Mcpt1

Nr4a1
Cbx3
mt-Co2
Jun
Jchain
Mcpt2

Pim1
Notch2
Xist
Dusp1
Iglc2
Nccrp1

Atf4
Skil
Fau
Neat1
Iglc1
Gm15848

Zfand5
Kdelr2
Gnb2l1
Ubb
Txndc5
Prr29

Fosb
Slc39a1
Btg1
Hspa8
Gm43291
C1qb

Ppp3ca
Ncoa3
mt-Nd1
Jund
Cd79a
Ltb

Ddx5
Lrrc58
Eef2
Alox5ap
Trp53inpl
Gpx4

Ptbp3
Upf1
Gm10709
Klf6
Iglv1
Mif

Zfos1
Rbm15
Eef1a1
Zfp36l2
Mzb1
Aif1l

Jarid2
Alkbh5
mt-Nd3
Tspo
Slpi
Krt8

Picalm
Kdm6b
Gm8730
Dnajb1
Derl3
Gata3

Cmip
Insig1
Wnk1
Fxyd5
Ssr4
Lum

Dusp5
Otub1
mt-Co1
Cd48
Edem1
Mdk

Pip4k2a
Fn3krp
Vps37b
Ccnd3
Pou2afl
Ndufa1

Mat2a
D17H6S53E
Crem
Pmaip1
Hsp90b1
Cfp

Tob2
Mcmbp
Bcl2l11
Fcer1g
Fkbp11
Crybb2

Ndel1
Wtap
Tgfb1
Lsp1
Sec11c
Cib1

Mel1
Marf1
Srrm2
Arhgdib
Vpreb3
Klrg1

Gna13
Abhd2
Ptpn18
Bin2
Sdc1
S100a9

Ythdc1
Yme1l1
Stat3
Zfp36
lgkv3-7
Kcnk1

Ubc
Soat1
Ssh2
Cyp7b1
Ccr10
G0s2

Pde4b
Cdk6
Gm42418
Itgb7
Iglv3
S100a3

Plekho2
Hsf2
Ubl3
Tsc22d3
Lax1
Platr3

Cbl
Ric1
Gcnt2
Zbtb32
Tnfrsf17
PISD

Sf3b1
4933434E20Rik
Eif3h
Atp5c1
Pdia4
Sri

Ctage5
Paip1
Klf13
Plp2
a
Cma2

Eif4g3
Lyrm4
mt-Co3
Sin3b
Xbp1
C1qa

Tiparp
Pdcd4
Map3kl
Eif4a1
Eaf2
Cited4

Stk38
Rrn3
Slc3a2
Itm2c
Spcs1
Serpinb1a

Dock10
B4galtl
Mrfap1
Ier5
St6gal1
Lysmd2

Jmjd1c
Timmdc1
Oaz1
Enol
Cd55
Prdx5

Herpud1
St13
Nsa2
Cd209e
Edem2
Foxs1

Ankrd11
Bmp2k
St8sia4
Ms4a6c
Rein
Id2

Brd2
Dfna5
Ywhaz
Sema4a
Lman1
Lamp1

Clk1
Kmt2d
Gpcpd1
Egr1
Endou
Rac2

Csrnp1
Dnase1l3
Ago2
Fgd2
Hid1
Nrgn

Gm26917
2310035C23Rik
Smc6
Rhob
Gm26826
Bcam

Pten
Klhl9
Itpkb
Capns1
Mgat3
Clic3

Ddx21
Tmf1
Son
Fcgrt
9230117E06Rik
Trbc1

Gnaq
Gm15800
Pmepa1
Hnrnpk
Gm15634
Cxcr6

St3gal4
Acot2
Ahr
Pepd
Actg2
Ly9

Wsb1
Zscan26
Luc7l2
Ifi30
Gm17096
Gem

Alcam
Ppm1h
Fam43a
Lmo1
Gm9796
Tnfsf11

Kdm7a
Pan3
Kras
Ccl9
Txndc11
Vsig2

Ifrd1
Myef2
Ifnar1
Capzb
Chchd10
Capg

Gm6133
Lrrc8a
Tsix
Pdcd10
Il5ra
Plekhs1

5031425E22Rik
Slc2a12
Dph3
Coro1a
Bhlha15
S100a10

Tm9sf3
Pfas
Gng5
Gltp
Znrf3
Limd2

D. Myeloid cells LP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7
topic_8

Cpa3
Lyz2
Cd74
Malat1
S100a9
2810417H13Rik
Mcpt1
Ccl2

Cma1
S100a4
H2-Aa
Mmp13
S100a8
Stmn1
Mcpt2
Hspa1a

Mcpt4
Ifitm3
H2-Abl
Apoe
G0s2
H2afz
Igkc
Gm26522

Tpsb2
Ccl9
H2-Eb1
Dnase1l3
Retnlg
Tubb5
Igha
Dnajb6

Fcer1a
Ms4a4c
Retn1a
Ccl8
Il1b
Ptma
Jchain
Ccl7

Hs3st1
F13a1
H2-DMb1
Lilra5
Cxcl2
Birc5
Mcpt9
Tmem261

Gata2
Chil3
Mgl2
Clec1b
Gm5483
Ube2c
Ifitm1
Nr4a2

Cited4
Thbs1
H2-DMb2
Ccl4
Wfdc21
Mcpt8
Cd63
Gm6133

Cyp11a1
Id3
Tmsb4x
Amica1
Lrg1
Rrm2
Cma2
Mrpl30

Tph1
F10
H2-DMa
Acp5
Asprv1
Hist1h2ap
Apol9b
Jtb

Furin
Serpinb10
Aif1
C6
Lcn2
Ppia
Iglc2
Ppp3ca

Rab27b
Ifi27l2a
Tmem176b
Apol7c
Irg1
Spc24
Ctla2a
Jarid2

Slc45a3
Gpx1
Cd83
Gas6
Ccrl2
Hmgb2
Itgae
Serinc3

Cel1
Crip1
Lyz1
Pla2g7
Il1f9
Hmgb1
Apol9a
Idh2

Il13
Al839979
Tmem176a
Stab1
S100a11
Nusap1
Mzb1
Zfos1

Il1rl1
Ace
Cd209a
Gas1
Msrb1
Ccnb2
Otop1
Poldip3

Itga2b
Cst3
Slamf8
Pla2g2d
Mrgpra2b
Top2a
Cpne5
Panx1

Cited2
Ly6c2
Mmp12
Ftl1
Dusp1
Tuba1b
Prnp
Fam96a

Fam110c
Smpdl3a
Axl
Mertk
Stfa2l1
Spc25
Gzma
Ppp1r9b

Creb3l1
Ifitm6
Cxcl16
Sash1
Hcar2
Cdca3
Pga5
Pigt

Rgs13
Fn1
Gm15056
Apol10b
Pglyrp1
Cdc20
Iglv1
Bckdha

Tpsab1
Lgals3
Pltp
Adamdec1
Marcksl1
Ccna2
Kcnn4
Fh1

Cyp26a1
Plac8
Pdgfb
Gm19434
Nfkbia
Cks1b
Htra1
Rtf1

Serpinb1a
Fau
Psap
Ubc
Fth1
H2afx
Asb17os
Snhg6

Slc18a2
Nupr1
Mrc1
S1c15a3
Trem1
H3f3b
Creg1
Grsf1

Gmpr
Ccr2
Mpeg1
Ccl3
BC100530
Cdca8
Ldlrad4
Rsl24d1

Rprm
Arpc2
Mt1
C1qa
Igfbp3
H1f0
Thsd4
Zc3h7a

Ero1l
Galnt9
Slamf9
Atf3
Csf3r
Aurkb
Adgrg1
Eif4e3

Il4
Apoc1
Ctss
Cebpa
Clec4e
Tpx2
Colec11
Dtx3l

Cd200r3
Ly6c1
Ccl12
Ppbp
HP
H2afv
Sec14l2
Dram2

Glul
Tppp3
Gatm
Cd81
Cebpb
Ran
Iglc3
Dock2

Kit
Tnfsf13os
Rgl1
Cxcl1
Slc16a3
Kif22
BCl2l15
Sertad2

Lat
Vim
Sdc3
Klf6
Steap4
Hmgn2
Ssr4
Tnfrsf13b

Alox5
Stxbp6
Itgb5
Ctsl
Mfap4
Cks2
Speg
Srsf6

Gchfr
Shfm1
Ppfia4
Ms4a7
Ly6g
Ube2s
Zcchc18
Mbnl1

mt-Atp6
Dmkn
Ctsh
Vps37b
Clec4d
Alyref
Fkbp11
Tmem192

Lat2
Wfdc17
Cfp
Pgf
Il23a
Asf1b
Urocl
Tcea1

Prss34
Pitpna
Ctsc
Csf1r
Mrgpra2a
Pbk
Ulk4
Cat

Poln
Cd52
Plxdc2
Pmepa1
Osm
Ccnb1
Ldhc
Slk

Klk8
B2m
Ifi30
Rgs1
Chil1
Fbxo5
Iglc1
Prdx2

4932438H23Rik
Cd300lg
Il22ra2
Sat1
Cxcr2
Ranbp1
Gm43291
Gm26825

Slc6a13
Clec4a3
B4galt6
Fcna
Mxd1
Ncapd2
Fermt2
Vps41

Avil
Lmo1
Plekho1
Rhob
Cyp4f18
Cenpa
Ppa1
Smim20

Socs2
Arpc1b
Batf3
Gpx3
Gadd45b
Ska1
Ndrg2
Pabpn1

Smco4
Ahnak
Rogdi
Tsku
Plpp3
Racgap1
Mro
Psma5

Ier3
Actr3
Dab2
AF251705
Cdk2ap2
Cit
Cux2
Phf20

Lxn
Emp1
Amdhd1
Ltc4s
Ltb
Rad51
Adamts1
Vav1

Gpr171
Hopx
Tbc1d9
C1qc
Mmp8
Anp32b
Slc6a9
Os9

Adk
Glud1
Sdc4
Irf8
Dhrs9
Mcm6
Mbtps1
Comt

Gata1
Ms4a8a
Bvht
Hal
Ctsd
Ncapg
6030468B19Rik
Mfsd1

E. ILCs LP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7

Rnase4
Calca
Il22
Id2
Malat1
Ccl5
Dusp5

Gda
Hs3st1
Cd83
Tmem59
Shisa5
Gzma
Bcl2a1d

Rcbtb2
Areg
Odc1
Dbp
Aim2
Klrd1
Serpinb9

Tcrg-C1
Il13
Cx3cl1
Itm2b
Amz2
Ms4a4b
Rgs1

Upp1
Il4
Cxcr5
Med23
Tnfaip8l2
Klre1
Klrk1

Ly6g5b
Ccl1
Cd74
Bcl2
Il18r1
Klra3
Gimap4

Cd163l1
Hes1
Nrp1
Tmx2
Pdcd4
Sh2d1a
Tmsb10

Lrrn2
Il17rb
Il17f
Paqr7
Gm26917
Klra9
Pim1

Ucp3
Lgals7
Gpx1
Cep57
Itch
Klra7
Cd69

Gapdh
Homer2
Dil1
Ttc14
Aldh3a2
Eomes
Irf7

Ppp1r14c
Il5
Igkc
More1
Cd96
Samd3
Pfn1

Pcp4
Gata3
Tox2
Uqcc1
Icos
Serpinb9b
Serpinb6b

Aprt
Deptor
H2-Ab1
Stat5b
Pnisr
Gzmb
Bhlhe40

Abi3bp
Ptpn13
Gem
Prkd3
Dhcr24
Tyrobp
Mxd1

Serf2
Ly6a
Prss2
Sec62
Crebzf
Ccl4
Hk2

Ucp2
Hba-a1
Foxq1
Vhl
Cebpz
Sema4a
Fasl

Cxcr6
Kcnn4
Lmna
Cept1
Sap30bp
Cd2
Hcst

Dmrta1
Ccr4
Cacna1g
Smg6
Gab3
Ccr5
Gimap3

Rbpms2
Rxrg
Foxs1
Tnfaip1
1600014C10Rik
Trdc
Nabp1

Cox6bl
Sub1
Parvb
Rnfl14
Fus
Nkg7
Serpinb1a

Ptprz1
1700061F12Rik
Adra1b
Ncln
Fam65b
Phactr3
Tnfaip3

Sla
Cntnap2
Fcgrt
Mcfd2
Stk19
Il21r
Slc16a6

Uqcr11
AA467197
Ramp1
Phc3
Rsrp1
Itgam
Selplg

Capg
Ptgir
H2-Eb1
Bod1
Spns1
Irf8
Litaf

Efhd1
Il10
Fam110a
Snapin
Cab39l
Lgals1
Smap2

Atp5j2
Nfkb1
Bst2
Tmem11
Rbm39
Gzmk
Lgals3

Gm13180
Lmo4
Hoxa7
Smn1
Hbp1
Actb
Gadd45b

4933431E20Rik
Pparg
Hebp1
Gimap1
Luc7l2
Gramd3
Vps37b

2010107E04Rik
Plaur
H2-Aa
Pitpnb
Slc7a6os
Anxa2
Pim3

Minos1
Il9r
Xist
Champ1
Spryd3
Klra5
Car2

Myeov2
Serpine1
Platr3
Phf20
Tmem127
Tm6sf1
Srsf12

Gabbr2
Seel
Sox4
Chd8
Them6
Gm15518
Abi3

Cfl1
Bmp7
Edf1
Pwwp2a
Bnip3l
Cd247
Ikzf2

Cryba4
Neb
Ostf1
Fra10ac1
Ypel3
Ifitm10
Lck

Sit1
Sox8
Rrad
Wdr82
Ankrd11
Cd52
Pltp

Gm26652
Lpcat2
Stab1
Zmynd8
N4bp2l1
Dusp2
Ggct

Gm9949
Samsn1
Fermt2
Jtb
Itpr2
Gpx8
Ncr1

Tns4
Alox5
Jchain
Cdc26
Rpusd4
BC094916
Neurl3

Ybx1
Gpr65
Slc16a2
Cnot1
Gm16223
Atp1b1
Vasp

Nop10
Abhd17c
Ninj1
Tor2a
Gps2
Klra4
Phlda1

Gimap9
Gm20186
Cd4
Zfp866
Oard1
Fcrl6
Ctsw

Rinl
Gm973
Cd81
1110034G24Rik
Kdelc2
Lat2
Nfil3

Tomm7
Epas1
Cd40
Nudt9
Cdc23
Sell
Clcf1

Tmem64
Ccr8
Krt25
Trim12c
Sbds
Ifng
RP23-218E6.4

Mrps33
D430036J16Rik
Adra2a
Otud6b
Mgea5
Tmsb15a
Ezr

Clic1
Cd6
5930412G12Rik
Cited4
Tk2
Klra1
Sept6

Pfdn1
Stxbp6
Cldn10
Nfx1
Usp7
Kcnj8
Pabpc1

P2rx7
9230102004Rik
Piwil4
Baz1b
Sirt7
Myb
Kctd12

Tnp2
Furin
Pacsin1
Zbtb43
Ing1
Ptprc
Ifngr1

Sema4b
Klf5
Marcksl1
Mphosph8
Hipk1
Ugcg
Cd160

topic_8
topic_9
topic_10

Fos
Zfp740
Il1b

Junb
H1f0
Ncoa7

Dusp1
Usb1
S100a8

Ier2
B930036N10Rik
Tubb5

Zfp36
Ppp1r10
Tuba1b

Jun
Puf60
Rasl11a

Klf2
Adprm
Hmgb2

Btg2
Bod1l
Stmn1

Nr4a1
Ppp2r1b
Ltb

Fosb
Dhx30
S100a9

Klf4
Pdcl
Ttyh2

Ppp1r15a
Slc35c1
2810417H13Rik

Pnrc1
Jade2
Cks1b

Egr1
Elk3
Hmgn2

Gm26532
Psmb10
Rgcc

Klf6
Tnrc6b
Ube2c

Iglc1
Osbpl2
Hspa1a

H2-T23
Rhob
Chad

Jund
Thap3
Rorc

Irf1
Mad2l2
Igf1r

Rnf2
Trim26
Cd7

Ier5
Sec16a
Sdc4

Fuca2
Golga7
Cks2

Sgf29
Pgm2l1
Ddc

Arid4a
Uxt
Birc5

Gm8797
Yif1a
Top2a

Ap3b1
Ccdc47
Hist1h2ap

Nt5c3
Tpp1
Apoe

Ip6k1
Wdr45b
Cbx3

Uvrag
Mcpt1
Pbk

Amn1
Pde4dip
H2afx

Mir142hg
Zfand2a
Pxdc1

Trrap
Rbm5
M1ap

Snhg12
Unc93b1
Smc2

Pias2
Lonp1
Asf1b

Vps41
Ppp3r1
Spc24

Per1
Ppp2ca
Retnlg

Ppp5c
Neil1
Ccdc34

Sgta
Xrcc6
Cenpa

Slain2
Brix1
Tipin

Tbc1d10a
Rbm15b
G0s2

Tiparp
Prmt1
Rrm2

Get4
Mdh1
Smc4

Xpa
Arcn1
Cdc20

Pomgnt1
Dynlt3
S1pr3

Cmip
Polr2g
Tifa

Vamp2
Map4
Siva1

Stim1
Zfp830
Ccna2

Sp2
Eif2b4
Fbxo5

H2-Q4
Pip5k1c
Dhrs3

F. Stromal cells PP

topic_1
topic_2
topic_3
topic_4

B2m
Glycam1
Dcn
Ccl21a

Cd81
Tm4sf1
Mt1
Cxcl13

Gm26917
Fabp4
Col3a1
Clu

Malat1
Ly6c1
Gsn
Ccl19

Igfbp7
Lrg1
Adamdec1
Acta2

Lmna
Ctla2a
Serping1
Mfge8

Eif3f
Tmem252
Rarres2
Apoe

Arpc1b
Pecam1
C3
Tagln

Ndufa4
Egfl7
Col1a1
Cxcl1

Gnas
Plvap
Rgs5
Cilp

Atp5l
Flt1
Col1a2
Cel2

Atp6v1g1
Scgb3a1
Cel11
Il33

Srsf5
Apold1
Plac8
Cxcl12

Ppib
8430408G22Rik
Clec3b
Actg2

Erh
Cldn5
Gem
Serpina3n

Ndufb11
Sox17
Bmp4
Ccl7

Rab2a
Ace
Col6a2
Bst1

Pfdn5
Cdh5
Cebpb
Serpina1a

Srsf3
Emcn
Ifi27l2a
Fmod

Pfn1
Esam
Mt2
Grem1

Cox6b1
Ptprb
Phlda1
Serpina1b

Uqcr10
Aqp1
Ms4a4d
Slc36a2

Sept4
Cd93
Fbln1
Cnn1

Gm10260
Esm1
Col6a1
Myh11

Socs3
Rasip1
Mgp
Art2b

Cope
Kdr
Tcf21
Actc1

Fkbp8
Cd36
Lrp1
Al838599

Ranbp1
Icam2
Crispld2
Serpina1c

Tagln2
Myct1
Cxcl14
Cr2

Ube2n
Cav1
Lpl
Gxylt2

Fos
Mgll
Spon1
Crym

H2-Q7
Edn1
Olfml3
Dclk1

Gm13889
Caim1
Spon2
Serpina1d

Fus
Arhgap31
Aspn
Myl9

Slc25a5
Ushbp1
Bgn
Parm1

Map1lc3b
Actg1
Fth1
Gm16685

Zfos1
Ackr1
Col14a1
Postn

Pnrc1
Gpihbp1
Sdc2
Chrdl1

Ube2i
C1qtnf9
Pid1
Colq

Atp5o
Klf2
Col6a3
Csn2

Ubald2
Mecom
Cd302
Prss12

Pkig
Cdkn1a
Mmp2
H2-M2

Chmp4b
Ptprr
Col5a2
Trf

Zcrb1
Rnd1
Pdgfra
Sostdc1

Mel1
Gngt2
Cygb
Dsc3

Maf1
Tek
Gm12840
Ctgf

Spop
Tspan13
Mmp10
Thbs4

mt-Atp8
Sema3g
Mxra8
Pcdh15

Dctn3
Adgrg1
Ctsk
Rtn4r

Ubb
St3gal6
Cpxm1
A230065H16Rik

G. T cells PP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7
topic_8

Igfbp4
Tmsb10
Arhgdib
Malat1
Klf2
Pdcd1
Ptma
Trbc1

Gm8730
Pfn1
Pik3ip1
Xist
Btg1
Il4
Ppia
Sepp1

Eef1a1
Sepw1
Gmfg
mt-Co1
Dusp10
Gal
Tuba1b
Cd53

Eef2
Ccnd2
Coro1a
Fyb
Vps37b
Nav2
Eif5a
Smc6

Gm10709
Cycs
Lsp1
mt-Co3
H3f3b
Tox2
Ran
Stk38

Gm10260
Psmg4
Cdkn2d
mt-Cytb
Ccr7
Cebpa
Slc25a5
Tcf7

Naca
Rrs1
Sell
mt-Atp6
Junb
Sostdc1
Mif
Hsdl1

Fau
Nolc1
Grap
mt-Nd5
Pnrc1
Angptl2
Pa2g4
Cdc42se1

Eif3f
Bel2
Scp2
Inpp4b
Ifngr2
5430421N21Rik
Nme1
Atp1b3

Pdlim4
Gar1
Tuba1a
Atrx
Gm8369
Gfra4
Ranbp1
Skap1

Tpt1
Map2k2
Tmem59
Zfp941
Rgs2
Tbc1d4
Serbp1
Atp1b1

Btf3
Zfp593
Al467606
Stx16
Gpcpd1
Rgs10
Atp5g1
Add3

Eif3k
Rpf2
Emc9
Zmynd12
Frat2
Gpm6b
Fbl
Mycbp2

Crip1
Atn1.1
Def6
Rb1cc1
Dusp5
Cxcr5
Hmgn1
Tmem234

Pabpc1
Trmt10c
Rnf114
Map1a
P2ry10
Bcl2a1b
Ddx39
Tspan14

Gm10269
Srm
Samd9l
Taco1
Tnfaip3
Cd200
Eno1
4930523C07Rik

Eif3e
Tmem248
Rsrp1
Ufsp1
Zfp281
Smco4
Ybx1
Prkd2

Eef1b2
Rsl1d1
Ostc
Gm28306
Bambi
Izumo1r
Eif4a1
Egln2

Nacc2
Med28
Mpnd
Vwa1
Cd28
Ascl2
Uqcrq
Lamtor2

Nsa2
Ywhaq
B3galt4
Prrc2c
Il4ra
Vdr
Apex1
Rp9

Gm13546
Gng5
Sgk3
Zkscan8
Btg2
Il21
Anp32b
Itk

Eif3h
Impdh2
Triap1
4933427l04Rik
Cxcr4
Adam33
Tcp1
Ms4a6b

Cox4i1
Mlx
2410002F23Rik
Gm27241
Ssh2
Ucp2
Banf1
Ikzf1

Gm26888
Mettl1
Ric8
Bcl11b
Ptp4a1
Gna14
Nop10
Card19

2010107E04Rik
Rasgrp2
Rgs19
Ssbp2
Ets2
Cdk2ap2
Prdx1
Itm2a

Eif3i
Pwp2
Glud1
Cul9
S1pr1
Ptprcap
Psma7
G3bp2

Tsga10ip
Armc1
BC029722
Rbm39
Tagap
Chn1
Hnrnpa3
Il17ra

Psmb1
Synj2bp
Ppp1ca
Gm16152
Gm20186
Lgals1
Uqcc2
Raf1

Atp5g2
Atad3a
Psap
Zmym5
Arid5a
lgkv3-2
Ppa1
Zfp292

Pfdn5
Abce1
Rbm10
Ankrd12
Csrnp1
Sh2d1a
Snrpe
Usp53

Hnrnpa1
Psmd3
Smarcd2
Vps13a
Gpr18
Rac2
Mcm2
Faah

Uqcrh
Nop16
Leprotl1
Fus
Dnajb9
Maf
Hprt
Ndrg3

Slpi
Psme3
Mettl9
Tmx4
Gpr183
Krt17
Erh
Actr10

Use1
Ddx18
Sat1
Tmem40
Socs3
Gm2762
Ndufa12
Klf7

Eif4b
Myd88
Bin1
Ddrgk1
Nabp1
Fgf2
C1qbp
Hgs

Snrpf
Trmt1
Vps4a
Cecr6
Maff
Gm9885
Cox7b
Pde12

Gltscr2
Aars
Ankrd13a
Oxt
Mirt1
Sh3gl3
Lsm7
Gimap6

Uqcrfs1
Msl2
Phyh
Erich4
Trim13
Vamp8
Snrpd2
Rasgrp1

Myeov2
Gps1
Ubald1
Gm44226
Ifnar1
Serpinf1
Atp5j
Mir142hg

2700060E02Rik
2810004N23Rik
Limd2
Gm26559
Prkca
Il9r
Atp5j2
2410016O06Rik

Vipr1
Fam50a
Med25
Zbtb20
Fosl2
Ctsb
Tubb5
Slc35b3

Gnb2l1
Lsm12
Pafah1b2
Gm28044
Rnf125
Ubl5
Prmt1
Trac

Gm17541
Dnaja3
Gtf3a
RP23-272F2.2
Sgms1
Fam20a
Cox6a1
Ncoa2

Tomm7
Ccnd3
Map4k2
2810030D12Rik
Il2rg
Fst
Ncl
Cd3d

Srms
Polr2h
Ppa2
Arhgef17
Bcl2l11
Bcl2a1d
Stmn1
Toporsos

Emg1
Utp18
Tbc1d10c
Adam6b
Gramd3
Actg2
Srsf3
Upf2

Sec61g
Nfkbib
Gm15675
2610528J11Rik
Sgip1
Smox
Grwd1
Mlec

Tbc1d16
Nop2
Daxx
Plch2
Tubb2a
Cpeb1
Lyar
Tpp2

mt-Co2
Pisd
Slc28a2
Hist1h2ad
Gypc
Dhx34
Gpn1
1600020E01Rik

Gm6096
Thap7
Exosc7
Pcdhgb2
Prdx6
Kirrel3
Mrpl23
Rnf167

topic_9
topic_10
topic_11
topic_12
topic_13
topic_14
topic_15
topic_16

Hspa1a
Wdr89
Ctla4
Dusp2
Actb
Ccl5
Cd8b1
Ifi27l2a

Hspa1b
Gm11808
Il10
Foxn3
Pdcd4
Gzma
Ly6c2
Shisa5

Hsp90aa1
Uba52
Sapcd1
Stag2
Abhd2
Tyrobp
Ly6c1
Ass1

Hspa8
Gm10073
Tnfrsf4
Igkc
Cbx3
Fcer1g
Lcn4
Tspan32

Ubb
Gm9843
Klrg1
Chic2
Wtap
Gzmb
Cd8a
Ecm1

Gm26825
Gm6133
Penk
Arf6
Ptp4a2
Xcl1
Ggt1
Samhd1

Jun
Gm9844
Areg
Cnppd1
Kdm6b
Tcrg-C4
Ly6a
Cd4

Dnaja1
Gm26917
Hmgb2
Snapc3
Mcmbp
Cd7
Tmem108
Ifi203

Dnajb1
Gm10036
Cd83
Sox4
Notch2
Dapk2
Adgrb2
Gimap3

Klf6
Gm2000
Samsn1
Pcgf5
Gm26771
Tcrg-C2
Nkg7
Igtp

Hsp90ab1
Gm10263
Ikzf2
Asf1a
Fxyd4
Cited4
Glipr2
Trav9-1

Gnai2
Gm9493
Tnfrsf9
Maea
Upf1
Klra5
Rcn3
Stat1

Grb2
Grcc10
Axl
Zfp330
Actr2
Klri2
Thy1
Ltb

Actg1
Gm10116
Batf
Ugcg
Marf1
Cd244
Gm43698
S100a10

Hsph1
Nme2
Dhrs3
Tbc1d17
B4galt1
Tcrg-C1
Ccr9
Trav9d-1

Fos
Gm10250
Apoe
Smim19
D17H6S53E
Zmat4
Kcnc1
Gpr83

Lcp1
Gm42418
Ebi3
Celf1
Slc39a1
Spry2
Dapl1
Cyp4f18

Ppp2ca
Gm5093
Smpdl3a
Mysm1
Lrrc8a
Cd160
B2m
Cytip

Dynll1
Gm15013
Nusap1
2210016L21Rik
Tmf1
Gm156
Slc25a4
Capg

Jund
Gm8186
Pou2f2
Trip12
Fn3krp
Klra7
Klk8
Cd2

Calm1
Gm6576
Il17rb
Ubn1
Alkbh5
Klrc2
Plac8
H2-D1

Glycam1
Ddit4
Dusp1
Pten
Zbtb40
Ccl4
Racgap1
Gimap1

Slc3a2
AY036118
Ldlrad4
Tmem128
Ncoa3
Lgals3
Hcst
Cish

Srpk2
Gm7808
Mmd
Vps41
Paip1
Batf3
Eomes
Gm5424

Pitpna
Ighg3
Nfkb1
Chmp3
Arglu1
Klre1
Runx3
Trav9n-1

Phlda1
Psme2b
Rora
Cant1
Zc3hav1
Trdc
Tagln2
Gata1

Hspb1
Gm10320
S100a4
Pafah1b1
Kmt2d
Klre1
Ppic
St8sia6

Cacybp
Gm8797
Cybb
Sun2
Acot2
Cd200r2
Ifitm10
Gbp7

Fabp2
Eno1b
Rilpl2
Etnk1
Rbm15
Klra3
Ms4a4c
Vim

Tra2b
Clca3a1
Podnl1
Gramd1a
Dpysl2
Spp1
Eng
Txnip

Baz1a
Ttc7
Tnfaip8
Mtf2
Ppm1h
Ncr1
Tm6sf1
Iigp1

Slc38a2
Gm4950
Hey1
Mknk2
Ppp1r16b
Lrrk1
Ostf1
Zbp1

Gm42670
Gm17669
Il1rl1
Nufip1
Rap2b
Ckm
Lman1l
Cyb5a

Gm37170
mt-Atp8
St6galnac3
Gnpnat1
Pitpnc1
Clnk
Adgrg5
Tnfrsf18

Tra2a
Gm5786
Epas1
Hagh
Inpp4a
Htra3
Ehd1
Tnfrsf25

Cd40lg
Gm5239
Ltb4r1
Dock8
Inafm2
Klra9
Saraf
Arl6ip1

Cdk2ap1
Lfng
Gm3636
Armt1
Skil
Klri1
Osbpl6
Rtp4

Ccdc117
Gm4978
Atp6v0d2
Cdk11b
Ptpn22
Itga1
Dnajc15
Phf11b

Fabp6
Lhfpl4
Rab37
Ap1s1
Kdelr2
Fgl2
Slco3a1
Nxpe3

Nav1
Gm16519
Nt5e
Trmt2a
Lyrm4
Car2
mt-Nd1
Ccdc22

Taf10
Lrrc58
Trib1
Arl8b
Otub1
Trgv2
Tapbpl
1110032F04Rik

Ighg2c
Snhg9
Wisp1
Ldlrap1
Mon1b
Gm16602
Sorl1
Adgre5

Fabp1
Gm10020
Bhlhe40
Wdr3
Hsf2
Emilin2
AB124611
Chd3

Mrpl38
Rnaset2a
Krt18
Rbbp6
Insig1
Slc16a11
Psme1
Arhgap15

Slc25a20
Gm5426
Cd44
Stxbp2
Slc24a5
Gm19590
Trim30c
Cd81

Rabggtb
Ost4
Ckap2l
Ppm1b
Zscan26
Cd3g
Fcgrt
Znrf1

Ahsa1
Usp50
Lztfl1
Kif2a
Sema4b
1810041H14Rik
G0s2
Fsd1l

Swt1
Gm43062
Trappc1
Pias1
Ric1
Ccl3
5730508B09Rik
Spcs2

H60b
Gm10094
Tnfsf8
Txndc9
4933434E20Rik
Sh2d1b1
Sec61b
Slfn1

Ighv1-14
Rtn4rl1
Zfp36l1
Chchd7
Tc2n
Cyp2j6
Sidt1
Trav2

H. B cells PP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7

Plac8
Crip1
Malat1
Npm1
H2-Ab1
2810417H13Rik
Actb

H2-Aa
Aicda
Xist
Mif
Cd74
Stmn1
Klf2

Capg
Chrna9
mt-Atp6
Gm8730
Ifi30
Ube2c
Junb

Tmsb4x
sypl
mt-Co3
Eef1g
H2-Eb1
Cdca8
H3f3b

S100a11
Rgs13
mt-Co1
Ybx1
Pfn1
Ccnb2
Fos

Cd79a
Lipc
mt-Cytb
Pebp1
Il4i1
Nusap1
Ier2

S100a10
Scimp
mt-Co2
Hspe1
Tnfrsf13c
Tubb5
Jund

Ly6e
Laptm5
Rsrp1
Hsp90ab1
Marcksl1
H2afz
Btg2

Sapcd1
Sorbs2
Siglecg
Ranbp1
Swap70
Tuba1b
Nr4a1

Cd38
Pold4
mt-Nd4
Erh
Hspa1a
Tpx2
Ppp1r15a

Gm9843
Eaf2
Ebf1
Gm10709
Syngr2
Hmgb2
Dusp1

Arhgap24
Arpc3
Ptprc
Nme1
Ptpn6
Ccna2
Cd69

Gm6133
Anxa2
Rbm39
Cox7c
Actr3
Birc5
Btg1

Edaradd
Bfsp2
Snx29
Gm10260
Cfl1
Hist1h2ap
Rgs2

Cyp4f18
Gm3336
Gm42726
Hint1
Hvcn1
Kif22
Tsc22d3

Marcks
Eif3h
Mbnl1
Atp5b
Cd40
Plk1
Zfp36

Gm11808
Slpr2
mt-Nd1
Snrpd2
Grap
Cep55
Pxdc1

Cd72
Prr13
Ttc14
Gapdh
Myl12a
Esco2
Cxcr4

Ostf1
Gm32200
mt-Nd2
Atp5e
Dnaja1
Asf1b
Dusp2

Ccr1
Gh
Atrx
Slc25a5
Cyba
Cdca2
Jun

Gm9493
Neil1
Chd6
Eef1b2
Samsn1
Pbk
Ier5

Sh3bgrl3
Fth1
Fchsd2
Eno1
Ms4a1
Ptma
Myc

Fcmr
Ube2d2a
Mbnl2
Gm10076
Iep1
Nuf2
Stk17b

Fcrl1
Smco4
Klhl24
Atp5g1
Cd53
Cdc20
Kdm6b

Ifi203
Dap
PISD
Prdx1
Mif4gd
Rrm2
Rhob

St3gal6
Serf2
Ddit3
Chchd2
Hnrnpf
Cdca5
Ccr7

Bcl2
Coro1a
Rbm5
Npm3
Actg1
Hmmr
Egr1

Rdx
Kcng2
Tsix
Phgdh
Slc25a19
Top2a
Hist1h1c

Hhex
Ildr1
Cdkal1
Hnrnpa1
Grb2
Cenpe
Nfkbid

Sub1
Pla2gl6
Trim7
Eif3i
Hcls1
Neil3
Satb1

Sla
Cd79b
Arid4a
Pkm
Irf8
Sgol1
Plk2

D1Ertd622e
Clta
Tra2a
Eef1d
Nfkb2
Ckap2l
Klf6

Serpinb1a
Bzw2
Cwf19l2
Gnb2l1
Rab35
Bub1b
Vps37b

Hck
Stbd1
mt-Nd5
Uqcrq
H3f3a
Mxd3
Il2rg

Ephx1
Oaz1
Map3k14
Nop58
II21r
Ccnb1
Sdc4

Eef1a1
Smim14
Dock11
Tpi1
Trp53
Hmgb1
Srsf5

Mndal
Dram2
Msl2
Snrpf
Cotl1
Cks1b
Nr4a2

Ncf1
Commd4
Prpf38b
C1qbp
Zfp362
Cdca3
Ptp4a2

Pml
Apobec1
Zfp280d
Cox5a
Bzw1
Cdk1
Tgif1

Ypel3
Cpne5
Son
Fkbp1a
Apex1
Lmnb1
Gm26532

H2-D1
Gnb4
Scaper
Uqcr10
Vasp
Cdkn3
Rrad

Zeb2
Sept1
mt-Nd3
Serbp1
Eif5
Spc24
Egr2

Tpt1
Tcea1
Prpf4b
Ndufb2
Calr
Tk1
Rel

Trps1
Rhoh
Safb
Ndufab1
Arpc4
Bub1
Zfp36l2

Fcrla
Smagp
Gm43291
Mdh2
Arpc1b
H2afx
Abhd2

Gns
Glrx3
Ate1
Shmt2
Nfkbia
Spag5
Fosb

BC094916
Borcs8
Cspp1
Phb2
Erp44
Sgol2a
Cytip

Cd300lf
Nuggc
Slc4a1ap
Hspd1
Lyl1
Melk
Gpr183

Gm2a
Gm2447
Ncor1
Cox6c
Psme1
Cdc25c
Atf4

Slfn2
Mroh7
Sumf1
Pa2g4
Relb
Rad51ap1
Neat1

topic_8
topic_9
topic_10
topic_11
topic_12

Ifi27l2a
Chd4
Igkc
Iglc1
Ighg2b

Ptms
Myo1c
Igha
Ighm
Ighg3

Gm9844
Ythdf2
Ccr10
lgkv5-39
Ighg1

Med11
Fam173b
Jchain
Iglc2
Ighg2c

Cdk2ap2
Ttc1
Hsp90b1
Iglv1
Igkv3-7

Pkp3
lsg20l2
Tnfrsf17
Iglv3
Igkv4-72

Phf14
Apopt1
Edem1
Mzb1
Igkv4-63

Cd24a
Birc2
lgkv4-59
Six4
Igkv6-25

Fkbp8
Pptc7
Krtcap2
Cst3
Igkv5-48

Mrpl10
Mmgt2
Fkbp11
Apoe
Igkv4-53

Lsg1
R3hdm1
Ssr4
Il1b
Igkv3-4

Hp1bp3
Kdm2b
Cd28
Prg2
Igkv1-135

Trmt10c
Sgf29
Iman1
Klk4
Igkv4-86

Ppp2r1a
Slc15a3
Edem2
Igkv2-109
Igkv8-30

Sdhaf4
Srsf1
Ssr3
Gm11772
Igkv1-110

Tcirg1
Exoc2
Ckap4
8030442B05Rik
Igkv3-5

Cstf3
Oxr1
Sdc1
Clstn3
Igkv4-68

Ggta1
Mtf1
H13
Cacna1s
Slpi

Pum2
Asb7
Pdia4
Gm42917
AY036118

Vamp8
Naa35
Spcs2
Iglc3
Gm42418

Parvg
Hif1a
Klrg2
Ighv7-1
Lyz2

Nelfb
Acot9
Igkv10-94
Kctd17
Gm37511

Acot8
Cltc
Mgat3
Dnajb9
Igkv8-24

Szrd1
Snx15
Khdc1c
Chst1
Cxcl13

Rab5c
Ado
Kdelr3
Fam174b
Gm26917

Ddx54
Pop7
Anxa8
Gm28062
Cxcl9

Faim
Mrpl3
Gm35202
Col5a1
Igkv4-60

Mettl5
Ctu2
Nacc2
Tarm1
Ly6c1

H2-T22
Nxf1
Ccr9
Gabrr1
Ighe

Oat
Arv1
Sec24d
Gm28513
Clu

Slu7
Tbl1xr1
Mpzl2
Sirpb1c
Fabp2

Alyref2
Leng8
Trp53inp1
Wnk2
A230065H16Rik

Pex19
Gon4l
Gtf2a1l
Prph
Ly6c2

Ndufa8
Nagk
Prss57
Gm5103
Ighv1-76

Aco2
Wdr6
Ighv3-5
D6Ertd527e
Gm11175

Apls3
Dynlt1c
Ly6g
Epyc
Fabp1

Atg101
Sema4d
Pls1
Cdh19
Igkv10-96

Il16
Lpcat3
Entpd1
Ceacam18
Mfge8

Rinl
Tmx2
Ppib
Asb16
Ighv1-62-1

Zdhhc7
Siah1a
Spcs1
1700011l03Rik
Ifitm3

Aftph
Fam53a
Pla2g5
Casq2
Ighv11-2

Slc30a9
Atxn2l
Fkbp2
Fam71b
Igkv6-23

Necap2
Ufm1
Lgals1
Lhfpl2
Mmp25

Tmem59
Gm5900
Fkbp14
Gm17590
Serpina1c

Prkcd
Ehmt2
Mpo
Slc6al9
Tmem176b

Hnrnph2
Bsdc1
Hoxd3os1
Cplx1
Igkv3-1

Scly
Zfp628
Nodal
Slc9a4
Igkv4-71

Oaz2
Sp110
Gm43121
Abcd2
Ccl2

Napg
Dhrs3
Txndc5
Inmt
Igkv4-50

Dync1li1
Polb
Gm15533
Xrra1
Serpina1a

I. DCs PP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7

D13Ertd608e
Cst3
Actb
mt-Co3
S100a4
Malat1
Fscn1

Cox6a2
Xcr1
Pfn1
mt-Co1
H2-DMb2
Hspa1a
Ccl22

Ly6c2
Naaa
Cfl1
mt-Atp6
Napsa
Hspb1
H2-M2

Bst2
Aif1
Ndufa1
mt-Co2
Cd74
Gm26825
Nudt17

Klk1
Tlr3
Cox6c
mt-Nd1
Ltb
Gm42726
Ccl5

Iglc3
H2-Aa
Myl6
mt-Cytb
Ifi30
Arhgap30
Ccr7

Ctsb
Cd207
Arpc4
mt-Nd2
Sucnr1
Pnisr
Cacnb3

Ly6c1
Ppt1
Atp5j2
mt-Nd4
Cfp
Hspa1b
Crip1

Cd8b1
Fam149a
Cox6b1
Tpt1
Cyp4f16
Prpf38b
Lad1

Slpi
H2-DMbl
Mif
mt-Nd3
Pglyrp1
Rbm25
Prg3

Grn
Tlr11
Myl12a
Fau
Gsn
Ubb
Tmem123

Rnase6
P3h2
2010107E04Rik
Wnk1
Limd2
PISD
Il4i1

Klk1b27
Cd52
Psmb3
Pabpc1
Cdh17
Swt1
Tnfrsf4

Siglech
Vwf
Usmg5
Eif3f
Clec4a2
Rsrp1
Tmprss11d

Irf8
Sult1a1
Capzb
Map3k1
Mdh2
Dnajb1
Socs2

Cd209d
A530099J19Rik
Uqcr11
Cirbp
Lpl
Gls
Gm16685

Ctsl
1700009J07Rik
Arpc5
Zfp106
S100a6
Ankrd11
Tnfrsf11b

Fcrla
Cxx1a
Arpc1b
Traf4
Rasgef1b
Ankrd61
Epsti1

Snx5
Eef1b2
Crybb2
Mbnl1
H2-Oa
Tmem55b
Tspan3

Sh3bgr
Cxx1b
Atp5e
Cdv3
H2-Ob
Rnf152
Nptx2

Serp1
Plpp1
Tma7
Eef2
Stk32c
Zfp280d
B2m

Pir
Hepacam2
Arhgdib
Xist
Gbx1
4833420G17Rik
Il12b

Upb1
RP24-416M6.5
Mrps21
Mir142hg
Asphd1
Golga1
Tdh

Gm5547
Psmb9
Cox7b
Fam107b
Tmem141
Tspyl2
Aire

Scimp
Fgd2
Ubl5
Ddx3x
Prdx6
Gm26522
Slc1a3

Pgls
Acvrl1
Ost4
Eef1a1
Siglecg
Ogt
Insm1

Dnajc7
BC028528
Lrrc58
Stat3
Arhgef2
Bdp1
H2-K1

Smim5
Eif3k
Serf2
Gltscr2
Tmem132c
Phip
Anxa3

Cybb
Stfa2l1
Tomm7
Sp140
Ggta1
Eif4a2
Lamp1

Lair1
Gramd2
Ppp1r18
Gnb2l1
S100a5
Gm42787
Cd63

Mpeg1
Gatm
Rab5c
Skil
Gabarapl2
Clk4
Nid1

Lefty1
Mctp1
Arpc2
Tacc1
Fbrsl1
Dhx30
Eno2

Pld4
H2-Ab1
Chchd2
Dock2
Ppp1r14a
Gdap10
Ankrd33b

Ly6a
Fuca1
Ndufv3
Kxd1
Ffar2
Lpin2
H2-D1

Nucb2
E030013l19Rik
Psmc5
4933434E20Rik
Rgs12
Zfp638
Syt1

Atp2a1
Rab32
Smdt1
Zfos1
Clec4a4
Smg1
Eno3

P2ry14
Cd36
Cox6a1
Aes
Lcp1
Akap9
Dkk2

Ptprcap
Dnasel13
Vapa
Cox7a2l
Lysmd2
Tor1b
Aard

Ccr9
Ece1
Ufm1
Defa24
M6pr
Gm28707
Zmynd15

Dap
Khk
Pdrg1
Gm26853
Syngr2
Tor4a
Slc7a10

Sell
Naga
Gm15848
Use1
Rp2
Akap8
Id2

Paqr5
Tifab
Arpc5l
Usf2
Slc6a13
Dhx36
Iscu

Robo3
Olfm1
Pfdn2
Lrba
Gdi2
Cspp1
Cd200

Klra17
Naalad2
Ndufa2
Serinc1
Rogdi
Hsp90aa1
Efnb2

Fbxl13
Gm28411
Fdps
Tomm20
Sh3bp1
Uvssa
Asprv1

Sema4b
Proser2
Gpx1
Csde1
Dlc1
Trim24
Prg2

Myh13
Tnfrsf22
Gpsm3
Whsc1l1
Chst10
Kdm3b
Tmem158

Cdh5
Rnf144b
Wdr1
Amnl
Myo1b
Nxf1
Tm4sf5

Blnk
Tbxas1
Akr1a1
Dennd1b
Nav1
Tyk2
Slco5a1

Lifr
Zfp652os
S100a10
Gm8730
Sirpa
Wdr13
Hgd

topic_8
topic_9
topic_10
topic_11
topic_12

Ptma
AY036118
Ccl4
Il1b
Ccl21a

Stmn1
Gm26917
Cel3
Lyz2
Nfkbia

2810417H13Rik
Uba52
Gpr171
Plet1
Mcpt1

Tmsb10
Igkc
Plaur
Il22ra2
Dusp2

Ccnb2
Gm42418
Fth1
Ifitm6
Junb

Vim
Gm10073
H3f3b
Ifitm3
Cd7

Ranbp1
Jchain
Klf2
Atox1
Tmem176b

Ube2c
Gm10076
Hist1h1c
Gp2
Sox4

Ran
mt-Atp8
Cd69
Csf1r
Bel2

Cks1b
Hist2h2aa1
Jund
Ccr1
Mcpt2

Anp32b
Gm10260
Ncf1
Ass1
Ier2

Rrm2
Gm21762
Rilpl2
Tarm1
Trbc1

Hmgb2
Gm10116
Fos
Mcemp1
Shisa5

Hmgb1
Gm11175
Btg1
Srgn
Dusp1

Cdca7
Igkv4-72
Herpud1
Sirpb1c
Xcl1

Tubb5
Nme2
Stk17b
Epcam
Mfge8

Tuba1b
Igha
Ubc
Tnni2
Nrgn

Dut
Gm20721
St8sia4
Csf2rb
Igfbp7

Cenpm
Gm8797
Neat1
Ctsc
Dcn

Cdk4
Igkv4-63
Tsc22d3
Mmp12
Apoe

Pa2g4
Gm28727
Gm26532
Sec61b
Spry2

H2afx
Gml0020
Cxcr4
Lgals3
Tnfsf11

Cdkn3
Gstp1
Tsc22d1
Msrb1
Ifitm1

Snrpd1
Hist1h2a1
Sub1
Dab2
Trbc2

Birc5
Eno1b
Irf1
Igsf6
Wfdc18

Hnrnpf
Gm9493
Ier5
Havcr2
Cd82

2700094K13Rik
Igkv3-4
Cytip
Ear2
Tmem176a

Ppia
Ighv11-2
Fam46c
Itgax
Il18r1

Mcm7
Gclm
Ptger4
Clec4n
Rorc

Nusap1
Grcc10
Evi2a
Fgl2
Cyr61

Srsf2
Gm6576
Zfp36l1
Csf2ra
Hilpda

Eif5a
Igkv4-68
5430427O19Rik
Acp5
Ikzf2

Impdh2
Dynlt1b
Zfp36l2
9530059O14Rik
Ighv1-85

Srsf3
Iglv1
Zc3h12c
Ctsz
Hes1

Npm1
Gm11127
Dyrk3
Adgre1
Prr7

Rbm3
1810009A15Rik
Slc3a2
Gm5150
Ccl19

Nudc
Igkv3-7
Lca5l
Pilra
Gem

Nel
Igkv5-48
Smc6
Hfe
Cited4

Pttg1
Cd79a
Jakmip1
Sat1
Cd37

Erh
Ighv9-1
Il12a
Sirpb1b
Dkkl1

Mcm2
Gm9843
Dusp18
Agpat4
Ddit4

Snrpf
Ighv5-9
Mef2c
Rrad
Chd3

Mcm6
Gm17275
Dusp5
Eps8
Igfbp4

Mcm3
Tespa1
Arrdc3
Tmsb4x
Nr4a1

Dnph1
Sft2d1
Ldlrad4
Gngt2
Cd3g

Banf1
Pgk1
Incpint
Gm2a
Nedd4

Hnrnpk
Fabp2
Ddit3
Timd4
Ier3

Mcm5
Gm26809
Rab7b
Cd86
Csf2

Pcna
mt-Nd4l
Fam174a
AF251705
Pim1

Ccnb1
Gm8186
Ifnar1
Fcer1g
Tgif1

J. Myeloid cells PP

topic_1
topic_2
topic_3
topic_4
topic_5

Ifitm3
Eef1a1
S100a9
Cpa3
Mcpt1

Eyz2
Gm8730
S100a8
Mcpt4
Mcpt2

Ey6c2
Fau
G0s2
Cma1
Mcpt9

Ace
Gm10709
Cxcl2
Cyp11a1
Cd63

S100a4
Eef2
Retnlg
Gata2
Ifitm1

Ear2
Actb
Gm5483
Tpsb2
Cma2

Plac8
mt-Atp6
Il1b
Il4
Pga5

Ly6c1
Cox4i1
Cxcr2
Hs3st1
Gm10354

Gm15987
Npm1
Lrg1
Il1rl1
Speer4e

Thbs1
Eif3h
Ecn2
Ubb
Prnp

Ms4a4c
Sh3bgrl3
Asprv1
Ccl4
Itgae

Chil3
Tpt1
Stfa2l1
Dnajb1
Ldhc

Clec4a3
Rbm3
Il1f9
Furin
Gm2a

Clec4a1
Gapdh
Wfdc21
Rab27b
Sec14l2

F13al
Naca
Msrb1
Cited4
Gm21190

Ifitm6
Eif3f
Marcksl1
Il13
Ctla2a

Ifi27l2a
Eef1b2
Mrgpra2b
Jun
Itgb6

Cst3
Eif3e
S100a11
Srgn
Apol9a

Sat1
Pabpc1
BC100530
Ccl2
Gzmc

Ccl9
Atp5e
Chil1
Fos
Htra1

Lrp1
Wdr89
Trem1
Ccl3
Tjp1

Ptpro
Pfdn5
Csf3r
Slc45a3
Cttn

Adgre4
Ppib
Mmp9
Klk8
Adgrg1

Cybb
2010107E04Rik
Fth1
Egr1
H19

Ifi205
Arhgdib
Clec4e
Junb
5830473C10Rik

Pid1
Atp5l
Irg1
Serpine1
Ldlrad4

Colec12
Cox5b
Steap4
Gchfr
Hey1

Ryr1
Gpi1
Clec4d
Itm2c
Ddit4

Rap1a
Atp5h
Tnfaip2
Cyp26a1
Cpne5

Nupr1
Atp5d
Pglyrp1
Pdcd1lg2
Gm17019

Tspan17
Ssr4
Il1rn
Rgs1
Apol9b

App
Polr1d
Hcar2
Chst1
Tspan8

Ifngr1
Eif3k
Mxd1
Fcer1a
Ikzf4

Mpp1
Tomm7
Cdk2ap2
Slc24a3
Nphs2

Hpse
Psmb1
Cxcl3
Angpt1
Speg

Pira2
Serf2
Il1r2
Glul
Al838599

Rhou
Cox7a2l
C5ar1
Serpinb1a
Abca13

BC028528
mt-Co2
Stfa2
Fosb
Irrc36

Pparg
mt-Nd1
Gadd45b
Tnfaip8
Atp13a4

Slc12a2
Aldoa
Slc16a3
Plgrkt
Asb17os

Ms4a8a
Atp5f1
Dusp1
Cited2
Gm9758

Nfil3
Sec61b
Rasip1
Itm2b
Otop1

Arl5c
Atp5o
Cd9
Hs6st2
Gdf11

Gm14548
Acbd6
Cebpb
Zmat4
Mcam

Smpdl3a
Ppard
Slfn1
Nfkbid
Tmem143

Cd300e
Npm3
Cd300If
Adamts9
Zbtb49

Sowahe
Uqcrh
Mrgpra2a
Rfc2
Fam151a

Gpx1
Ndufa6
Ly6g
Tsc22d1
Fermt2

F10
Gnb2l1
Cyp4f18
Creb3l1
Ccnb1ip1

Tifa
Tma7
Pilra
Rgs18
Tchp

topic_6
topic_7
topic_8
topic_9
topic_10

Gzmb
Prss34
Cd74
Cdkn1a
Uba52

Malat1
Mcpt8
H2-Aa
Bhlhe40
Gm26917

Slco2b1
Lgals1
H2-Eb1
Hnrnpll
AY036118

Fndc5
Ran
H2-Ab1
Hist1h1c
Gm42418

Xist
Stmn1
C1qa
Chmp5
Gm10076

Hes1
Akr1c18
C1qb
Uap1
Tmsb10

Psd3
Ube2c
C1qc
Hint2
Gm10073

Gnaz
Ms4a3
Apoe
Ccdc107
Gm10116

Gm11697
Erh
H2-DMb1
Txnl4a
mt-Atp8

Srsf5
Ptma
Pla2g2d
Kmt2e
Igkv4-72

Bfsp2
Nme1
H2-DMb2
Maz
Vim

Lmo4
Ranbp1
Tmem176a
Srsf4
Nme2

Gm12840
Cdca3
Cd81
Mrps24
Eno1b

Rnf19b
Cdca8
H2-DMa
Ppm1g
Crip1

Zbtb20
Nusap1
Tmem176b
Eif4g2
Gm10260

Fosl2
Ppia
Cxcl9
Hnrnpr
Gm11175

Gm20186
Ccna2
Gm15056
Ifrd1
Hist2h2aa1

Lag3
Tmem160
Mmp14
Ahr
Klf2

mt-Nd3
Dut
Cxcl16
Yif1a
S100a10

Csrp3
Anp32b
Spon1
Zfp91
Gm9844

Susd6
Eef1g
Dnase1l3
Ankrd12
Gm6576

Smarca1
Ap3s1
Apol7c
Anapc5
Gm17275

Ccnd2
Tomm20
Lyz1
Lcp2
Il2rb

Nap1l5
Dad1
Acp5
Ids
Ahnak

Rab4a
Nop10
Il22ra2
Alad
Snx22

Tpbgl
Tacc3
Prg3
Stub1
Ighv9-3

Slc6a6
Lsm6
Aif1
Nabp2
Gm7676

4933407L21Rik
Parvg
Ms4a7
Scamp1
Gm20721

Grik5
Snrpd2
Mrc1
Sde2
Gm10020

Muc1
Pgam1
Gas1
Wbp2
Igkv4-86

Ssbp3
Uqcr11
Kcnj10
Vat1
Gm9493

Ccdc138
Ndufa12
Ctsh
Il22
Gm8186

Smo
Gng12
Cp
Larp7
Il23r

Tgfbr1
Tubb5
Ifi30
Sec31a
Pgk1

Zfp941
Banf1
Adamdec1
Ralbp1
Ccr6

Ikzf2
Sumo3
Cd209b
Chchd3
Kmo

Zfp638
Cel6
Timd4
Tdg
Hnrnpa3

Smyd4
Timm17a
Axl
Ddb1
Ighv11-2

Rgs2
Atp5g1
Rab3il1
Crem
Nr1d1

Pdgfrb
Mrpl18
Slc1a2
Gpbp1l1
Igkv3-5

Zfr
2810417H13Rik
Wnt6
Trp53
Gm28727

Patz1
Cyc1
Cxcl14
Hs6st1
Sik1

Fam120c
Srsf6
Il27
Vdac3
Gstp1

Akap13
Tuba1b
Sdc4
Neurl3
Hmga1

Ugcg
C1qbp
Clec9a
Hmces
Diaph1

H3f3b
Klk4
Apo110b
Matr3
Styx

Cx3cr1
Ppan
Lgmn
Cmas
Gm11127

Dnaja1
Cdk1
Cabp4
Gsk3b
Tnfsf13

Stard10
Anp32e
Nuak1
Wtap
Gm10146

Fam129c
Dkc1
Tlr12
Dcun1d5
Sft2d1

K. ILCs PP

topic_1
topic_2
topic_3
topic_4
topic_5
topic_6
topic_7

Lgals3
Shisa5
Cel5
Il22
Xcl1
Rgs1
Hes1

Slc6a20a
Ltb
Gzma
S100a4
Gimap4
Txk
Calca

Ffar2
Bel2
Klrel
Ode1
Bcl2a1b
Akap13
Il13

Upp1
Tmem123
Klra3
Piwil4
Ctsw
Itch
Hs3st1

Lrrn2
Eif3l
Ccl4
Parvb
Cd52
Hist1h1c
Areg

Serpinb1a
Fam173b
Klra9
Cd83
B2m
Aqr
Il4

Ly6g5b
Trmt112
Klra7
S100g
Bcl2a1d
Smad7
Cel1

Ppp1r14c
Ciz1
Ms4a4b
Sdc4
Gpr55
Plgrkt
Hilpda

C4b
Timm9
Lgals1
Hebp1
Pfn1
Wdr47
Gata3

Id2
Limd2
Tmsb4x
Il17f
Klrk1
Mndal
Homer2

Tgm3
Blmh
Cel3
Ptges
Hopx
Pum2
Ccr4

Pcp4
Mat2b
Cd2
Ldhb
Coro1a
March7
Serpine1

Ucp3
Dpf2
Gzmb
Rasl11a
Serpinb6b
Afg3l2
Hba-a1

Ptprz1
Tia1
Ctla2a
Ramp1
Ikzf2
Gimap8
Vps37b

Rnase4
H2-D1
H2afz
Tnfsf11
Ncr1
Phf3
Ptgir

Amical
Srsf1
Nkg7
Prr29
Hcst
Gimap6
Rxrg

Eps8l3
Lias
AW112010
Adra1b
Serpinb9
Avl9
Samsn1

Rbpms2
Cnih1
Sh2d1a
Cldn10
Cd160
Tecpr1
Il17rb

Actn2
Supt4a
Klra1
Hmgn3
Il2rb
Il18r1
Lmo4

Tns4
Spin1
Klrd1
Grb10
Il4ra
Tcp11l2
Il5

Cdh10
Poldip3
Ifitm10
Cryaa
S100a11
Gramd1a
Deptor

Asb2
Dctn2
Eomes
Ccdc184
Ptma
Foxj3
Stxbp6

Rax
Aspscr1
Klra4
Nrp1
Sh3bgrl3
Cdk12
Dusp10

Ccr9
Zfp788
Ly6c2
Gpx1
Ms4a6b
Fus
Lgals7

Ryk
2700094K13Rik
Itgam
Cd81
Rbm3
Irak2
Scel

Cxcr6
Csk
Anxa2
Lta
Cox8a
Lgals8
Ramp3

Krt4
Golga7
Ctsd
Cntn1
Lsp1
Jakmip1
Slc7a8

Maf
Cd2bp2
Irf8
S100a6
Klrb1f
Cdkn1b
Furin

Cd163l1
Commd2
Tm6sf1
Cd82
Ubald2
Mthfs1
Nfkb1

Prelid2
Rnf8
Clip4
Fam110a
Fasl
Mkln1
AA467197

Pabpc1l
Vars
Gfra2
Mrfap1
Cxcr3
Hipk1
Sox8

Rinl
Serinc1
Ctla2b
Fth1
Phgdh
Usp48
Sub1

Ucp2
Prmt3
1700025G04Rik
Foxs1
Trac
Bclaf1
Gm973

Aqp3
Mrpl15
Klrb1c
Espn
Serpina3g
Dusp11
Gm20186

Krt79
Ino80b
Rac3
Igfbp7
Irg1
AU020206
Cntnap2

Ddx25
Golga3
Sema4a
Bst2
Nabp1
Atg12
Pparg

Zfp414
Rpe
Serpinb9b
Adm
Slc16a6
Snrk
Frmd4b

S100a10
Nfkbil1
Cma1
5930412G12Rik
Cfl1
Peli1
Il9r

Hbegf
Rbm4b
Ugcg
Ube2e3
Gm19585
Galnt7
Lrrc52

Gstm5
Tmx3
Klra10
Cpn1
Psmb8
Rbm34
Spty2d1

Gjb2
Bloc1s4
Sgk1
M1ap
1-Sep
Git2
Ptpn13

Klrb1b
Cct8
Kcnj8
Krt25
Cd274
Esco1
Ccrl2

Amhr2
Zkscan3
Ccr5
Ostf1
Ifngr1
Zfp36l2
Neb

F2r
Nudt18
Ptprc
Nkx6-2
Gimap3
Mxd4
Plaur

6720489N17Rik
Polr2j
Ly6c1
Ecm1
Lck
Taf8
Itk

Tg
Eif4a2
Gramd3
Ccr6
Psme2
Rhoh
Icos

Hs6st2
Cs
Atp1b1
S100a3
Ckm
Ccdc91
Crem

Prpsap1
Nae1
Ccr2
Batf3
Cd7
Kdm6a
Esm1

Ppt2
Nono
Qrfp
Chad
St8sia4
Nosip
Cxcl2

Capg
Ikbkg
Samd3
Mpzl1
Nhp2
St6galnac3
Gpr65

topic_8
topic_9
topic_10
topic_11
topic_12

Cd74
Junb
Gm8730
AY036118
Fos

H2-Aa
Gadd45b
Eef1a1
Gm26917
Dusp1

Malat1
Nfkbia
Gm10260
Gm42418
Jun

H2-Eb1
Nr4a1
Gm9493
Uba52
Ier2

H2-Ab1
Fosb
Gm9843
Gm11175
Egr1

Hspa1a
Nfkbid
Gm10709
mt-Atp8
Zfp36

Hspa1b
Btg2
Gnb2l1
Igkv4-72
Klf6

H2-DMb1
Tgif1
Gm11808
Igkv3-7
Rhob

H2-DMb2
Tagap
Naca
Igkv4-63
Klf2

Gm26825
Pim1
Fau
Igkv3-4
Ccl21a

Atrx
Ubb
mt-Co3
Ighv9-3
Cd69

Mef2c
Phlda1
mt-Co2
Gm20721
Tsc22d3

Dnajb1
Klf4
Gm2000
Ighv11-2
Rgs2

H2-DMa
Jund
Eef1b2
Eno1b
Oser1

Dcstamp
Ier5
Npm1
Gm11127
Tnf

H2-Oa
Zfp36l1
Eef1g
CAAA01147332.1
Mcpt2

Siglecg
Maff
Gm10036
Igkv4-68
Gm26532

Iglc1
Spry2
Wdr89
Igkv1-110
Egr2

Ly86
Ubc
Eif3h
Gm8797
Mcpt1

Tnip3
Btg1
Gm6133
Igkv3-5
Thra

Cited4
Hspa5
mt-Co1
Igkv6-25
S100a9

Ms4a4c
Gem
Uqcrh
mt-Nd4l
Zfp395

Sacs
Pnrc1
Cd3g
Gm10073
Snhg12

Srrt
Tuba1a
Hspe1
Siglech
Ifitm1

Golga4
Mir142hg
Hnrnpa1
Gnai2
Lztfl1

Napsa
Tgoln1
Eif3e
1810009A15Rik
Polg2

Ctse
H1f0
Izumo1r
Tsix
Pias1

Zfp24
Eif1
Hspa8
Gm28727
H2-T23

Shprh
Morf4l2
Atp5a1
Rbm39
Kdm5a

Cacybp
Sertad1
Eif3f
Ier5l
Birc3

AC125149.3
Atf4
Cox4i1
Igkv5-39
2900060B14Rik

Hspb1
Tuba1c
Ccr7
Lyz2
Gm26802

Esd
Gm17056
Cct5
Pde4b
Dusp6

Arhgap30
Gm10827
Eif3k
Myl12b
Prrc2b

Iglc3
Herpud1
Tpt1
Zg16
Srpr

Gm12976
H3f3b
Gm10269
Iglv1
Serpina1b

Trav11
Sqstm1
Hsp90ab1
Gm10116
Hs3st3a1

Gm37170
Tubb4b
Cox7a2l
Ighv5-4
Mcpt4

Cdadc1
Bcl10
Plac8
Gclm
Chic2

Igkv9-124
Stk24
Fbl
Gm17275
4833403J16Rik

Gstm1
Plrg1
Cct4
Ighv9-1
Fam21

Ppp1r3d
Hnrnpf
Eif3m
Ndfip1
Cox10

Ltbp2
Ensa
Btf3
Ighv1-62-1
Zfp322a

Natd1
Tuba4a
Snrpe
Fabp2
Tgds

Calcoco1
Mgat4a
Atp5b
Nme2
Etaa1

1700030J22Rik
Rgcc
Gm10263
Ncor1
Dyrk3

Zzz3
Usp37
Gpi1
Igkv5-48
Amn1

Gm6297
Ddx3x
Anp32b
Coxl6
Hsf1

Lgi4
Csf2
Zfos1
Rapgef6
Hmox2

Antxr1
Atxn1
mt-Atp6
Psap
Tmem252

TABLE 5

The enriched peaks and their associated genes in the

intestinal KLRG1 + ILC2s stimulated in vitro with

α-CGRP or control, related to FIG. 6.

Peaks enriched in ILC2s treated

Gene
with α-CGRP

0610009L18Rik
84328 (−4512), 84336 (−139),

84337 (+789), 84339 (+1590),

84340 (+4057)

0610010K14Rik
78877
(−2199)

1110008F13Rik
16421
(+331)

1110037F02Rik
25171
(−31942)

1110065P20Rik
29118
(−661)

1600029D21Rik
61961
(−17707)

1700011E24Rik
115690
(+143781)

1700011H14Rik
97385
(+71505)

1700017B05Rik
62437
(−5689)

1700021F05Rik
69422
(−8)

1700025G04Rik
5808
(+12)

1700034J05Rik
46595
(+7037)

1700040L02Rik
70667
(+254838)

1700056E22Rik
8006 (+165268), 8004 (+229579)

1700060C20Rik
16591 (−8759), 16596 (+12303)

1700101G07Rik
17691
(−600954)

1700106J16Rik
80781 (+204591), 80785 (+232776)

1700112E06Rik
96208
(+879765)

1810013L24Rik
105927
(+884)

2310015B20Rik
70735
(−23766)

2410127L17Rik
121182
(−31040)

2610002J02Rik
31919
(−15877)

2610507B11Rik
79746
(+526)

2610524H06Rik
36919
(−936)

2810025M15Rik
6281
(−31463)

2810403A07Rik
21226
(+1528)

3110018I06Rik
89138
(+7546)

3110021A11Rik
44783
(+926)

3110079O15Rik
3284
(+89139)

3930402G23Rik
54431 (−77281), 54430 (−76792),

54412 (−66834), 54409 (−64079),

54395 (−54062), 54392 (−53111),

54391 (−52665), 54365 (+207770)

4833420G17Rik
95571
(−32739)

4921513D11Rik
114933
(+72723)

4921513I03Rik
73819
(+130219)

4930404H24Rik
16106
(−48419)

4930426L09Rik
9753
(−43)

4930432M17Rik
23061
(+44725)

4930438A08Rik
77812
(−35454)

4930447C04Rik
86799
(+153671)

4930524B15Rik
75933
(−75371)

4930538K18Rik
28775
(+13346)

4930597O21Rik
42288 (−101856), 42274 (−819)

4931440P22Rik
20165
(+154)

4932438H23Rik
109571 (−4035), 109563 (+12493)

4933406P04Rik
68275
(+162741)

4933415A04Rik
76309
(−420)

5031425E22Rik
32592
(+17874)

5033430I15Rik
92261
(+115889)

5730507C01Rik
85150
(+95808)

5830418K08Rik
60145
(−136432)

5930422O12Rik
55096
(+88982)

8430427H17Rik
16137 (+355), 16136 (+809)

8430432A02Rik
1106
(−413)

9230102O04Rik
9123
(−108534)

9230109A22Rik
101059 (−263217), 101021 (+4006)

9430020K01Rik
115987 (+603), 115988 (+19036)

9930013L23Rik
50858
(−30655)

9930021J03Rik
121699
(−559)

A1bg
102424
(+66950)

A230083G16Rik
45188
(+912)

A330050F15Rik
114458
(+1922)

A3galt2
29324
(−31257)

A630091E08Rik
51231
(+28383)

A930004D18Rik
9612
(−10247)

A930011G23Rik
35707
(−44408)

AI118078
62238
(+514)

AI314180
26741 (−30), 26740 (+518)

AI481877
26785
(−21190)

AI593442
62110
(+491132)

AW554918
116568
(+3191)

Abca1
26454
(−36323)

Abca2
10018 (−136), 10019 (+412)

Abcb1a
32308 (+53254), 32311 (+63017),

32314 (+115280)

Abcb1b
32308 (−84816), 32311 (−75053),

32314 (−22790), 32323 (+41708)

Abcb4
32323 (−53862), 32330 (+330)

Abcc1
106302
(+610)

Abcc3
81037
(−80045)

Abcd3
23064
(+78627)

Abhd12b
86641 (−42098), 86642 (−36811)

Abhd17c
50858
(+34736)

Abi1
9858
(+877)

Ablim1
123468
(−139686)

Abr
79500 (−133068), 79499 (−114022)

Acadl
2425
(−33360)

Acads
36984
(+27907)

Acer2
27375
(+9351)

Acot1
87778
(−10085)

Acot11
28098 (−36161), 28075 (+49934)

Acot2
87778
(+11556)

Acot7
31732
(+998)

Acox2
95628
(+43905)

Acoxl
14900
(+200492)

Acpp
65638
(+30745)

Acsl6
77479
(−16096)

Actb
39157 (+3897), 39156 (+4467),

39153 (+5862)

Actbl2
95067
(+233930)

Actc1
14137
(+1837)

Actg1
84340 (−4193), 84339 (−1726),

84337 (−925), 84336 (+3),

84328 (+4376), 84327 (+5002),

84315 (+43313)

Actn4
48096
(−10570)

Actr3
4201
(+8619)

Actr8
96616 (+13886), 96618 (+15186),

96620 (+15722)

Acvr1c
11959
(+169986)

Acvr2a
11599
(−404201)

Adam10
64023
(+865)

Adam9
54836
(−232)

Adamts17
49598
(+272963)

Adamts20
104685
(−2322)

Adamts14
21722
(+21507)

Adarb1
71056
(−1257)

Adck1
88222
(+106440)

Adcy1
75018 (−395889), 75023 (−389427),

75025 (−388199), 75026 (−387948),

75027 (−387534), 75031 (−384813),

75032 (−384150), 75034 (−382941),

75035 (−381981), 75049 (−294451)

Adcy9
105732
(−36090)

Add1
33368
(+1175)

Add2
42992
(−3093)

Add3
123123
(+1079)

Adnp
17613
(+89724)

Adnp2
119244
(−47152)

Adora2a
70877 (+3550), 70883 (+9781)

Adprhl2
29227
(+20268)

Aebp2
46123 (−2515), 46145 (+27408),

46154 (+50763)

Aff1
35968 (+737), 35989 (+102286)

Aff3
805
(−10925)

Aff4
77169
(+903)

Agap1
3452 (−324213), 3462 (−123)

Agap2
74129
(+25249)

Agfg1
3005
(+290)

Aggf1
94171
(+45691)

Agl
23011
(−6108)

Agpat3
71188
(−54322)

Ahdc1
29863
(+1030)

Ahnak
120568
(+1978)

Aifm2
70260
(−5342)

Akap12
67491 (−166178), 67489 (−154343),

67472 (+118704), 67471 (+120447)

Akap6
86127 (−55095), 86148 (+129795)

Akap7
68683 (+2009), 68661 (+129124)

Akirin1
29069
(−46)

Akt2
47896
(+880)

Aktip
57460
(+330)

Aldhla2
64058
(−35278)

Alg13
125856
(+208421)

Alg2
26376
(+105378)

Alkbh2
36832
(−2753)

Alkbh5
78047
(+934)

Alpk3
50691
(−62915)

Alpl
30624
(+88307)

Amfr
57537
(−563)

Amhr2
105535
(−34087)

Amph
90502
(+5864)

Anapc10
56727
(+139316)

Ank
101132
(+345)

Ankfy1
79054
(−81509)

Ankrd1
122084
(−229547)

Ankrd13a
36902
(−1131)

Ankrd13c
24665
(+15755)

Ankrd17
35316
(−1041)

Ankrd44
1743
(+82)

Ankrd50
19362 (+20660), 19352 (+111205),

19347 (+204372)

Ankrd52
74367
(+302)

Ankrd55
95165
(+151125)

Ankrd63
14313 (+900), 14312 (+1153)

Ankrd9
89484
(−109)

Anks6
26337
(−186)

Ano10
67120
(+129511)

Ano6
104731
(+96795)

Ano8
56380
(+8369)

Anp32a
63022
(+169356)

Anp32b
26257
(+1755)

Anxa11
96387
(−11647)

Aoah
90599
(−701636)

Aoc2
82182
(−1278)

Aox3l1
1853 (+25522), 1854 (+26224)

Ap1ar
23241
(−133)

Ap3s1
117687
(+1181)

Ap5b1
120131 (−292), 120132 (+140)

Apbb2
34670 (−801), 34654 (+97117)

Apoa1
61750 (−208151), 61758 (−181311)

Apoh
83155
(−17034)

Apol8
103355
(+203)

Apool
125496
(+43)

Apopt1
89594
(+9634)

Aqp9
64058
(−17222)

Arap1
51577
(−4794)

Arap2
34198
(−748)

Arcn1
61597
(−62)

Areg
35399
(+1475)

Arfgef1
101
(+214)

Arg1
68683 (−369685), 68661 (−242570)

Arhgap12
116032 (+542212), 116031 (+542705)

Arhgap17
52743
(+151504)

Arhgap23
81476
(−10297)

Arhgap27
82468 (−35972), 82452 (−743)

Arhgap39
103308
(−4968)

Arhgap5
86106 (−11528), 86127 (+128211)

Arhgdia
84386 (−86), 84385 (+473)

Arhgef33
115026
(+84450)

Arid1a
30025 (−64017), 30018 (−788)

Arid1b
110306 (+736), 110308 (+1738),

110309 (+2355)

Arid2
104731
(−399935)

Arid4a
86713 (+727), 86714 (+1083)

Arid5b
70667 (−8332), 70620 (+151409)

Arl5a
11801
(+38247)

Arl6ip4
38003
(+71621)

Armc2
69276
(+129756)

Arntl
52206
(+813)

Arrb1
51359
(+914)

Arrdc4
49719
(−152)

Art2b
51617
(+102758)

Asap1
102684
(+48795)

Asap2
85161 (−35783), 85164 (+471)

Asb17
24619
(+5560)

Asb2
88929
(+21768)

Ascc1
70055
(−34060)

Ascl2
53960
(+1067)

Ascl4
72076
(+25046)

Aspg
89642
(+33750)

Asphd2
36675
(+9705)

Asxl1
16106
(+98526)

Atad2b
84775
(+628)

Atf1
105215
(+545)

Atf4
103787
(+3742)

Atg12
117687
(−1519)

Atg14
97330 (−81294), 97318 (+43834),

97317 (+45922)

Atg4b
3743
(−78)

Atl1
86614
(+42)

Atp10a
49309
(+703)

Atp12a
97846
(−88711)

Atp13a1
56058
(+828)

Atp1a1
22210
(+110520)

Atp1b1
6755 (−23507), 6753 (−389)

Atp2b1
72899 (−44), 72900 (+559)

Atp6v1a
107942
(+112880)

Atp6v1c2
85112
(+57031)

Atp8b3
71468
(+43050)

Atr
65233 (−4464), 65236 (+900)

Atrn
15125 (−62), 15126 (+441),

15130 (+47709)

Atxn7l3
82305
(−525)

Auh
92779 (−45201), 92778 (−43991)

Aven
14105 (+17028), 14107 (+20022)

Axin1
111319
(+2129)

Axin2
83174 (+853), 83175 (+1280)

Azi2
66721
(+13005)

B3galt6
32044
(−402)

B3galtl
39702
(+368)

B3gnt2
75639
(+168113)

B630019K06Rik
123796 (+609), 123797 (+1146)

BC005537
90992
(−729)

BC005764
71278
(+18677)

BC018507
93512
(−295)

BC023829
124712
(−393)

BC034090
6118
(+9525)

BC055111
28067
(+2930)

BC067074
95292
(+292356)

BC107364
21849
(+145742)

Baalc
101720
(+33833)

Bag3
53303
(+32297)

Bahcc1
84315 (+72282), 84327 (+110593)

Bai2
29573
(−33573)

Barhl2
36181
(+482683)

Basp1
101062 (−784), 101059 (+1388)

Batf
88020
(−25571)

Baz2a
74305
(−60)

Baz2b
12041
(−118876)

Bcas1
17789 (+52796), 17788 (+53298)

Bcl11b
89138
(+507424)

Bcl2l11
14900 (−70919), 14914 (+1408)

Bcl7c
53181
(−4359)

Bend6
427
(−231)

Bhlha9
79499 (−49029), 79500 (−29983)

Bhlhe40
44086
(−177943)

Bloc1s4
33510
(+52608)

Bmp2
15394
(−411468)

Bmp8a
29056 (−322084), 29005 (−72526)

Bmpr1a
96994
(−491)

Bmpr2
2025
(−610)

Bola3
42808 (+335), 42809 (+7332)

Boll
1789
(−87)

Bora
99645
(−130)

Bptf
83029
(+103878)

Brd2
112457 (+679), 112446 (+10617)

Brd3
10227
(−303)

Brd7
57364
(+51)

Brf1
89763
(+15074)

Bri3
39315
(+736)

Brwd1
110080
(+41533)

Btbd1
50782
(−257)

Btbd17
83423
(+9318)

Btbd2
71510
(−8750)

Btbd6
89763
(+8984)

Btc
35399
(+261823)

Btf3l4
28307
(+52132)

Btrc
122720
(+173971)

Bzw1
1853 (−89288), 1854 (−88586)

C130057N11Rik
16200
(−126047)

C1qtnf9
98100
(+3091)

C2cd2l
61509
(−45)

C2cd4c
71233
(+18558)

C2cd5
46249
(+106157)

Cab39
3080
(−24)

Cab39l
98003
(+115330)

Cables1
116231
(−42562)

Cabyr
116303
(−96962)

Cacna1a
57101
(+224303)

Cacna1d
96671
(+319870)

Cacna1f
123715
(+11275)

Cacna1g
81037
(+1079)

Cacng1
83112 (+131259), 83110 (+143818)

Cacng5
83141
(−338398)

Cadm4
47605
(+3383)

Calb2
58190
(−9503)

Calca
52371 (−9991), 52367 (+4726)

Calcb
52371
(−72295)

Calcrl
13183 (−46178), 13182 (−45893)

Calm1
88525
(−14923)

Camsap2
5111
(+376)

Camta1
31658
(−235)

Cand1
73729
(−147)

Capn13
114705
(+145746)

Capza2
40093
(+906)

Car8
24897
(+880669)

Carhsp1
105900
(+5465)

Casc1
46389
(+86196)

Casc3
81805
(−8376)

Cass4
17813
(+2909)

Casz1
31331 (+96556), 31332 (+97481)

Catsper2
14532
(+37)

Cbfa2t3
59252
(−1672)

Cbx2
84107
(+957)

Cbx4
84123
(+29276)

Cbx8
84123
(−15976)

Ccar1
70362
(−27)

Ccdc112
117644
(−182333)

Ccdc113
57707
(−26)

Ccdc167
111926
(+46865)

Ccdc23
28775
(+9375)

Ccdc32
14354
(+6081)

Ccdc6
70718 (+370), 70735 (+83797)

Ccdc64
37103
(+194)

Ccdc64b
110999
(−8813)

Ccdc71l
85555 (−39047), 85562 (+1990)

Ccdc83
51073
(−79700)

Ccdc88a
75833 (+333), 75834 (+131048)

Cck
67038
(+67224)

Ccnj
122311
(+633)

Ccr8
66901
(+6675)

Ccsap
59470
(+316)

Ccser2
97043
(−64625)

Cct8
109359
(−53)

Cd101
22177 (−25901), 22175 (−23137)

Cd180
94665
(+212637)

Cd247
6884
(−70)

Cd24a
69427 (+271), 69428 (+604)

Cd274
121613
(+18642)

Cd7
84481
(+21500)

Cd81
53979
(+3221)

Cd83
92015
(+538590)

Cd93
15804
(−78749)

Cdadc1
98003
(+41525)

Cdan1
14493
(−74800)

Cdc40
69165
(+177699)

Cdc42bpa
7649 (−537), 7650 (−135)

Cdc42bpg
120301
(+327)

Cdc42se2
77558
(−103)

Cdca4
89708
(−953)

Cdh17
25239
(+62479)

Cdk17
72296
(+1803)

Cdk2ap1
38035
(−56315)

Cdk5r1
80064
(+327)

Cdkn1a
111808 (−16697), 111820 (+23162)

Cdkn2aip
55629
(−314)

Cdkn2b
27577
(+11)

Cdon
61056
(+310)

Cdv3
65583
(+32810)

Cdyl
91520
(+82370)

Cebpb
17525
(+32)

Celf1
13335
(−167)

Celf5
71769
(+12001)

Celf6
62669
(+158)

Celsr3
66037
(+788)

Cenpv
78273
(−40)

Cep120
117853
(−88216)

Cep170b
89682
(−33515)

Cep76
118561
(+28863)

Cep78
120998
(−13406)

Cers2
21679
(+529)

Cgref1
33016
(−4388)

Chd2
49807 (−16892), 49777 (+34724)

Chd7
24960 (−153484), 24984 (+203),

25004 (+104971), 25005 (+108758),

25030 (+197591), 25061 (+383019)

Chdh
96635 (−3540), 96671 (+24593)

Chka
119808
(−83160)

Chmp4b
16200
(+8068)

Chmp6
84216
(−253063)

Chrd
106690
(+71603)

Chst10
821
(+99)

Chst14
14354
(+96815)

Cic
47728
(−128)

Cited2
67943
(−39215)

Ckap5
13391
(−19164)

Clasp2
66317
(−22232)

Clcf1
119913
(+1420)

Clcn2
106684
(−1605)

Clec16a
105995
(+102985)

Clic1
112655
(+287)

Clic4
30355 (−132), 30310 (+106721)

Clic5
113142
(+521526)

Clip1
37864
(−323)

Clk2
21257
(−1457)

Clk3
62515
(−74)

Clnk
33779 (−766803), 33765 (−755566),

33741 (−740455), 33731 (−733236)

Clstn1
31374 (−44475), 31380 (+203)

Clvs1
25004 (−473425), 25005 (−469638),

25030 (−380805), 25061 (−195377)

Clybl
100431
(−69754)

Cmah
90955
(+296404)

Cmas
46200
(+3524)

Cmc1
66734 (−76439), 66721 (+96576)

Cmip
58662 (−95547), 58676 (+333),

58689 (+30434), 58731 (+122279)

Cmtm4
57758
(−260)

Cnih
97207
(+62)

Cnn3
23051
(+15980)

Cnnm2
122943 (+1158), 122950 (+57771),

122952 (+75919), 122973 (+103921),

122974 (+107347)

Cnnm3
592
(+809)

Cnnm4
589
(−104)

Cnot6
76773 (+5766), 76772 (+6690)

Cnot7
55454
(−853)

Cnot8
77768
(−57539)

Cntn2
4789
(+22023)

Cobll1
12317
(−42)

Coch
86020
(+55)

Cog3
99322
(−97)

Cog6
19630
(+717630)

Col14a1
102053
(−111186)

Col17a1
123068
(+41047)

Col5a1
10259
(−121335)

Col8a2
29227
(+14642)

Colgalt2
5838
(+51900)

Commd6
99761
(+3077)

Cops4
35784
(+51380)

Cops5
90
(−1702)

Coro2b
63022
(+26359)

Cox4i1
59005
(+10363)

Cox5a
62466
(+1145)

Cpe
55896
(−14695)

Cpeb4
75933
(+17995)

Cpn1
122563
(+27176)

Cpn2
107107
(+79926)

Cpne5
111823
(+81256)

Cpox
108727
(+6627)

Cradd
72508
(+143746)

Cramp1l
111194
(−717)

Creb3
26019
(−1073)

Creb3l1
13435
(+60824)

Crebbp
105722
(−831)

Creld1
44295
(+11105)

Crem
115875 (−35074), 115859 (+37043)

Crispld2
58880
(−80566)

Crtc3
50610
(−159)

Cry1
72054
(−880)

Cryaa
112146 (+165145), 112151 (+170166)

Cryzl1
109662
(+34071)

Csf2ra
123656
(+1173)

Csnk1d
84481
(−26588)

Csnk1g3
117853 (−29344), 117883 (+82074)

Cspp1
90
(+1611)

Csrnp1
66851
(−7694)

Csrnp2
105255
(−57)

Ctdp1
119331
(−241609)

Ctdsp1
66790
(+225)

Ctf1
53181
(+556)

Ctgf
68584
(+40696)

Ctif
119004
(+328415)

Ctla2a
93257
(+3530)

Ctnnb1
66992
(−3)

Ctnnbip1
31374
(+23927)

Cttnbp2
40133 (−327500), 40132 (−327205)

Ctu2
59218
(+7846)

Cul1
41303 (+575), 41318 (+105759)

Cul2
115875
(−48599)

Cul4a
54532 (−69), 54533 (+652),

54534 (+26777)

Cul5
62157
(−2508)

Cxadr
109216
(+15558)

Cxcr4
4524 (−151682), 4523 (−151327),

4522 (−151056), 4514 (−147226),

4482 (−14132)

Cxxc5
116976 (−55780), 117023 (+46496)

Cyb561
82727
(−2397)

Cyp17a1
122915
(+52881)

Cyp1b1
114933
(+15641)

Cyp2r1
52367
(−68659)

Cysltr2
98981 (+121958), 98980 (+122429)

Cystm1
117071
(−62291)

Cyth1
84008 (+68087), 83995 (+113015)

Cyth2
48916
(−204)

Cytip
11959
(−27414)

D10Wsu52e
72076
(+4286)

D16Ertd472e
109216
(+259603)

D1Ertd622e
3835 (+1003), 3834 (+1146)

D5Ertd579e
33510
(−23093)

D630003M21Rik
16596
(+24910)

D830014E11Rik
36142 (−116115), 36153 (−78231)

D930028M14Rik
47705
(+29157)

Dag1
65954
(−16664)

Dand5
57140
(+9578)

Dapk3
71675 (+8936), 71676 (+10434),

71677 (+11324), 71679 (+14520)

Daxx
112386
(+1443)

Dbf4
32279
(−894)

Dcaf10
26167
(+1614)

Dcbld1
69716
(+493)

Dcun1d4
34960
(+11495)

Dda1
56380
(+8499)

Ddit4
70055
(−17009)

Ddost
30714
(−35320)

Ddx18
4179
(−39705)

Ddx59
5114
(+320)

Ddx60
55887
(−136733)

Dedd2
47705
(+38245)

Dek
92343
(+37)

Dennd2a
41056
(+106664)

Dennd4c
27362
(+2113)

Dennd5a
51971
(−8577)

Dennd6a
96426
(+380)

Depdc1b
94939
(+74455)

Derl1
102129
(+196203)

Dgat1
103231
(+12070)

Dgkd
3338
(−116)

Dgkz
13435
(−13251)

Dhcr24
28067
(+53270)

Dhx40
80575
(−54597)

Diap3
99610
(+462543)

Disc1
59572
(+388267)

Dkk4
54726
(+26300)

Dlgap1
114458
(−983546)

Dmbx1
28512
(−23291)

Dmxl1
117724
(+135855)

Dnahc17
84008 (−51196), 83995 (−6268)

Dnajb14
23887
(+3626)

Dnajc11
31666
(+904)

Dnajc12
70409
(−8904)

Dnajc13
65638
(−60156)

Dnajc25
26766
(+280)

Dnajc3
100110
(+987)

Dnase1l1
124857
(+3556)

Dner
3015
(−14170)

Dnmbp
122563
(−46988)

Dnmt3a
84644
(−233387)

Dock3
65772
(−38375)

Dock8
121440
(+53900)

Donson
109662 (−6139), 109657 (+30732)

Dopey1
64864
(+410)

Dot1l
71557
(+1085)

Dpm1
17631
(−978)

Dppa2
108167
(−10407)

Dppa4
108167
(+16335)

Dpt
6755
(−314870)

Dpysl4
53587
(+43970)

Dqx1
42752
(+123)

Drd3
107917
(−64292)

Dtl
8260
(+149454)

Dtnb
84644
(+1252)

Dtnbp1
92081
(−3047)

Dusp1
111351
(−26972)

Dusp10
8045 (+23153), 8059 (+113062),

8060 (+113414)

Dusp14
80310 (−832), 80305 (+12203)

Dusp16
45819
(+75737)

Dusp26
55063
(−63849)

Dusp5
123192 (−104881), 123212 (−32065)

Dusp7
65703
(+471)

Dvl3
106656 (+501), 106657 (+838)

Dync1h1
89392
(−109795)

Dynll2
80725 (−15444), 80724 (−35)

Dyrk1a
110004
(+150909)

E030011O05Rik
65312
(+31340)

E030025P04Rik
83193 (−109700), 83175 (+222740)

E130304I02Rik
48500
(+421)

E2f3
91064 (+343), 91063 (+883)

Ebf1
76366
(−72983)

Ebi3
113937
(+486)

Echdc3
8724
(−109715)

Ect2l
67999
(+96380)

Edem3
5714
(−139246)

Edil3
93882
(+12376)

Ednrb
99870
(+192732)

Efna5
114232 (−212140), 114231 (−201402)

Efna5
114239 (−2963), 114232 (+62470),

114231 (+73208)

Efs
97692
(+723)

Egln1
59554
(+27097)

Egln3
86265 (−439035), 86220 (−255275),

86191 (−109417)

Ehd2
47047
(−2262)

Eif3k
48096
(+8904)

Eif4h
38417
(+8940)

Eif5
89562
(+3773)

Eif5b
787
(+594)

Elac1
118855
(−4689)

Elf2
19500 (−809), 19499 (−246)

Elf4
124426 (−969), 124425 (−158),

124424 (+391)

Elk3
72296
(+148456)

Elmo1
90599
(+1864)

Elmsan1
87848 (−67517), 87840 (−26742)

Elovl7
94923
(+403)

Emb
95446
(−186553)

Eml1
89292
(+29804)

Emr1
114193
(−42522)

En2
32869
(−71576)

Enah
7901
(−71387)

Enoph1
35731
(−97)

Enpp1
68584
(+76020)

Enpp6
55572
(−245699)

Eogt
43646
(+42153)

Eomes
66734 (−251825), 66764 (+4148)

Epas1
115543 (+25522), 115556 (+35286)

Epc2
11695
(+50)

Epdr1
90590
(+101205)

Ephb3
106690
(−400025)

Epn2
78125
(−18186)

Eps15
28361
(+636)

Eps15l1
56525 (−73), 56504 (+90163)

Ercc3
116627
(−75300)

Ergic1
111353
(−12149)

Erich1
54620
(−120)

Erich2
12500
(+29360)

Erv3
15232
(−43388)

Esrp1
25171
(−67233)

Etos1
53339
(+126073)

Ets2
110057 (+152348), 110063 (+185876)

Eva1c
109525
(−385)

Evl
89292
(−102100)

Exoc6
122190
(−115170)

Eya2
17111 (+4445), 17112 (+18240)

Ezh2
41318
(+34951)

Ezr
110510
(−44626)

F2r
94185
(+54558)

F2rl1
94185
(−38661)

F3
23061 (−7495), 23064 (+13138)

F5
6727
(+39488)

F730035P03Rik
51388
(−41000)

F830045P16Rik
15056
(+151123)

Faah
28512
(+54709)

Faim
65375
(−21087)

Fam101a
38091 (−134250), 38112 (+49362)

Fam102a
10847
(−116)

Fam105b
101163
(−98)

Fam120a
92404
(−6851)

Fam122a
121412
(−220)

Fam129a
5714
(+44755)

Fam129c
56404
(−1558)

Fam131a
106677
(−1617)

Fam131b
41228
(+46)

Fam132b
3574
(+14303)

Fam13b
116834
(−528)

Fam151a
28075
(+16023)

Fam160b1
123468 (−5291), 123480 (+7775),

123482 (+14339), 123483 (+30232)

Fam161a
75722
(+136588)

Fam168b
484
(+367)

Fam171a2
82335
(+9245)

Fam174b
49807
(−181669)

Fam189a2
121391
(−144197)

Fam19a4
43646
(−46618)

Fam212b
22468
(+21623)

Fam219b
62466
(−15151)

Fam222a
36866 (+15655), 36872 (+48790)

Fam46a
64849 (−202755), 64825 (+6859),

64824 (+7329)

Fam49b
102684
(−273676)

Fam53a
33269
(+133251)

Fam53b
53449
(−11022)

Fam65b
90955
(−14824)

Fam72a
4704
(−2600)

Fam76b
60018
(+70446)

Fam78a
10714
(+44925)

Fam83d
16651 (−86636), 16701 (+408)

Fam83h
103134
(−5827)

Fam84b
102424
(−29240)

Fam86
105854 (−146773), 105844 (−113039),

105843 (−112018), 105838 (−96450),

105835 (−42)

Farp1
100220
(+274579)

Fasl
6556
(+37650)

Fbrsl1
36476 (+31272), 36472 (+71481)

Fbxl14
44738
(+688)

Fbxl17
114273
(+139)

Fbxl18
39157 (−7436), 39156 (−6866),

39153 (−5471)

Fbxl21
93052 (−19890), 93057 (−16660),

93058 (−15262)

Fbxl3
99815
(−194)

Fbxo11
115774
(−56925)

Fbxo16
98430
(+77107)

Fbxo21
37174
(+25544)

Fbxo22
62228
(−58846)

Fbxo34
97317 (+49951), 97318 (+52039)

Fbxo47
81591 (−74933), 81585 (−61961),

81584 (−59173)

Fbxo6
31292
(−127)

Fbxw7
20874
(−241213)

Fbxw8
37192
(+85984)

Fcgr1
21849 (−12595), 21846 (+15778)

Fem1c
117644
(+31710)

Fermt1
15394
(−194785)

Fermt2
97188
(+130083)

Fes
50483 (−11720), 50482 (−11343),

50481 (−10858), 50479 (−9638),

50477 (−8702), 50476 (−8048),

50473 (−6222), 50472 (−5282),

50471 (−5100), 50470 (−4632),

50469 (−3691), 50468 (−3073),

50467 (−2157), 50466 (−1444),

50460 (+1991), 50456 (+4043),

50455 (+4415), 50454 (+4964),

50453 (+5304), 50452 (+5461),

50451 (+6122), 50450 (+6814),

50449 (+7008), 50448 (+8241)

Fgf9
97977
(−590)

Fhad1
31088
(−413)

Fkbp4
45428
(−58)

Fkbp6
38470
(+63530)

Fkrp
47217
(−1523)

Fli1
60770
(+31652)

Flii
78054
(−678)

Flot1
112845
(−155)

Flot2
79694
(+414)

Flt1
39498
(+294848)

Fmnl3
105111
(+74099)

Fndc3a
98981 (−217153), 98980 (−216682),

98943 (+90)

Fndc3b
18886 (−893), 18885 (−499)

Fnip2
20671 (+231535), 20629 (+324127)

Fosb
47399
(+1345)

Fosl2
33164 (−2760), 33165 (−1851)

Foxc1
91248
(−173945)

Foxf2
91248
(+6885)

Foxk2
84514 (+5034), 84519 (+34504)

Foxl2
65375
(+9679)

Foxn2
115774
(−318495)

Foxn3
88439
(+168522)

Foxo1
19617 (+931), 19630 (+31256)

Foxo6
28836
(−118484)

Foxp4
113559
(−352)

Frmd3
27209
(+217793)

Frmd4a
8585
(+512)

Frmd4b
43727
(+170316)

Frmd8
120211 (+41483), 120195 (+78474),

120194 (+78862), 120193 (+80132)

Frrs1
23011
(−63953)

Fry
39703
(−141361)

Fsd1l
26479
(+306)

Ftsjd1
58190
(−40251)

Ftsjd2
111924 (−22532), 111926 (+9549)

Furin
50490 (−1487), 50489 (−356),

50483 (+3096), 50482 (+3473),

50481 (+3958), 50479 (+5178),

50477 (+6114), 50476 (+6768),

50473 (+8594), 50472 (+9534),

50471 (+9716)

Fut8
87205
(+357)

Fxr1
19130
(+495)

Fzd5
2371
(−36)

Fzd6
101720 (−39358), 101722 (+317)

Fzd9
38470
(−35231)

Gabrr2
25612
(−29264)

Gad1
12500
(−23863)

Gadd45a
42295 (−3678), 42288 (+39029)

Gadl1
66527
(−520916)

Galk1
83633
(−7446)

Galnt1
116519
(+999)

Galnt2
59486
(+957)

Galnt4
72948
(−50)

Gan
58662
(+3337)

Gata3
9087 (+4898), 9078 (+9764),

9076 (+11737), 9075 (+11926),

9074 (+12534), 9056 (+21995)

Gatsl2
38338
(+67124)

Gcat
103611
(−27699)

Gcsh
58648
(−77404)

Gfm2
94336
(−24)

Gfod1
91913
(+41931)

Gfra4
15130
(+88478)

Git2
36902
(−51)

Gjb2
97904
(+125)

Gjd2
14137
(−37431)

Glcci1
39887
(+781)

Glce
62956
(−52144)

Glg1
58250
(+109703)

Gls2
74334
(+917)

Gltp
36888
(−2782)

Gm10113
92261
(+109906)

Gm10146
71188
(−40794)

Gm10234
43638
(+292572)

Gm10322
69980
(−100888)

Gm10335
67862
(−495717)

Gm10463
33165 (−1453), 33164 (−544)

Gm10517
7955
(−453)

Gm10655
62815 (+1550), 62776 (+329329)

Gm10699
54620
(−14)

Gm10766
14832
(−589)

Gm11077
46145 (−78377), 46154 (−55022)

Gm11114
64774 (−812952), 64811 (−124907),

64812 (−111346), 64819 (−26378),

64824 (+7022), 64825 (+7492)

Gm11146
109179
(+574310)

Gm11444
80411
(+5562)

Gm11696
83219
(+266)

Gm17669
118561
(+50086)

Gm20388
58880
(+1031)

Gm20458
16943
(+385)

Gm20503
26766
(+242)

Gm2178
96421
(+13239)

Gm21988
78877
(−161)

Gm3086
86615
(−50504)

Gm355
14914
(−463762)

Gm4968
45379
(+200568)

Gm4980
51375
(−33432)

Gm5148
19362 (−738021), 19352 (−647476),

19347 (−554309), 19283 (+83416)

Gm5258
3160
(+16358)

Gm5277
20551
(−55923)

Gm5475
105245
(+937)

Gm5634
123797
(+69476)

Gm5784
85150
(−776313)

Gm6020
123656
(+43355)

Gm6583
36675
(−26475)

Gm6658
57425
(−837)

Gm711
10173
(−1249)

Gm766
46225 (−66066), 46200 (+44180)

Gm7854
33824
(+885)

Gm8214
8006 (−186112), 8004 (−121801)

Gm8225
111351 (−7269), 111353 (+6580)

Gm8226
64774 (+75846), 64811 (+763891),

64812 (+777452), 64819 (+862420)

Gm8765
92500 (+403259), 92501 (+403540)

Gm9754
37192
(+4114)

Gm9869
62776
(−204664)

Gm9912
24417
(−144363)

Gm9920
102053
(−82982)

Gm9945
77217
(−389)

Gm9958
35316
(+22)

Gmcl1
43101
(−1)

Gmeb1
29746 (−9818), 29743 (−4599)

Gna13
83219
(+557)

Gnai1
32386 (+350143), 32385 (+379568)

Gnal
118501 (+45829), 118502 (+47696)

Gnaq
120998 (−134436), 121017 (+539)

Gnat3
32383 (−1918), 32385 (+18224),

32386 (+47649)

Gng12
42274
(+943)

Gng13
111246 (−116736), 111252 (−103555),

111255 (−52981)

Gng5
24342
(+1054)

Gnl3
96799
(−913)

Gnpda1
117249
(−9728)

Gnpnat1
97188 (−11233), 97184 (+5709)

Gnptab
72162
(+323)

Gns
73873
(+54115)

Golga4
66764
(−23826)

Golm1
93206
(+72509)

Gpbp1
95067
(+1168)

Gpc1
3679
(+140)

Gpd1
105165
(−11672)

Gpd2
11870
(−114082)

Gpr112
124613
(−4391)

Gpr15
108727
(+41889)

Gpr158
9799
(+596421)

Gpr34
123996
(−111340)

Gpsm1
10106
(+659)

Gpx4
71361
(+675)

Gramd1c
107942
(−9989)

Grap
78125
(−55394)

Grb7
81694 (+13328), 81695 (+14653),

81720 (+44918)

Grik5
47683
(−855)

Grlf1
47176
(−328)

Grn
82335
(+8122)

Grsf1
35267 (−674), 35266 (−76)

Gsg2
79119
(−36)

Gtdc1
11509
(−66839)

Gtf3a
39436
(−44431)

Gtpbp1
103713
(+32752)

Gucd1
70902
(+104859)

Gyg
18698
(−346)

Gzmb
97846
(−14097)

H1foo
44519
(+49026)

H2-Ke6
112423
(+12)

H2-Oa
112446
(+18790)

H2-T24
112891
(+26710)

H3f3b
83633
(+7797)

Haao
115317 (−340072), 115302 (−315074)

Hand1
77733
(−79722)

Hapln1
93882 (−706749), 93897 (+198854)

Hcn1
95552
(+40226)

Hcn3
21257
(−3142)

Hdac4
3605
(−121873)

Hdac4
3605
(+95344)

Hdac7
104891
(+44820)

Heatr3
57330
(+48)

Hectd1
86066 (−1144), 86065 (+241)

Hectd3
28624
(+642)

Helz
83110 (+24744), 83112 (+37303)

Hes1
107075 (−56585), 107077 (−55562),

107085 (−1019), 107107 (+122266)

Hey1
18339 (−101121), 18337 (−99877),

18336 (−99224), 18327 (−10338),

18326 (−2886)

Hhex
122190
(+2361)

Hhip
56727
(+206870)

Hif1a
86987 (−3566), 86991 (+1304),

87004 (+35512)

Hip1r
37900 (+547), 37916 (+25136),

37917 (+25591), 37919 (+26244),

37920 (+27395), 37922 (+28488),

37923 (+28907), 37924 (+29155),

37925 (+29550), 37926 (+29804),

37927 (+30037), 37928 (+30358),

37930 (+31219), 37931 (+31609),

37932 (+32128), 37949 (+44161)

Hipk3
13951
(−170)

Hist2h2bb
21846
(+8439)

Hivep2
67830 (−180), 67831 (+133),

67862 (+60982)

Hk2
42699
(−105612)

Hlx
8060 (+584824), 8059 (+585176),

8045 (+675085)

Hmgb1
39638
(−54)

Hmgb2
55776
(+960)

Hmgxb4
56600
(+30484)

Hmx2
53378
(+436)

Hnrnpa0
93122
(−456)

Hnrnpa3
12810
(+567)

Hnrnpd
35707
(+205485)

Hnrnph3
70377
(+39596)

Hnrnpk
93154
(+947)

Hnrpdl
35731
(−675)

Hnrpll
114968
(+46)

Hook3
54986
(−2148)

Hormad2
74657
(+179358)

Hps1
122487
(−412133)

Hps4
36674
(+298)

Hpse2
122487
(+196202)

Hs2st1
24211
(+162378)

Hs3st1
33779 (+1019), 33765 (+12256),

33741 (+27367), 33731 (+34586)

Hs6st1
526
(−114)

Hsd17b4
117768
(−87168)

Hsf1
103231
(+22436)

Hsf2bp
112165
(+160425)

Hsf4
57808
(+699)

Hspa13
108901
(−95102)

Hspa1b
112614
(+6630)

Hspb3
95299
(+33139)

Htra2
42752
(−3396)

Ibtk
64849
(+214274)

Icmt
31780
(+15805)

Icos
2158
(+25755)

Idh2
50367
(−60979)

Ier2
57101
(+23185)

Ier5l
10487 (+2157), 10486 (+4030)

Iffo2
30840
(−193046)

Ifit1
122056
(+21423)

Ifne
27519
(−59413)

Ift140
111194
(−444)

Ift172
33058
(+11382)

Igf1r
49644 (−108777), 49648 (−40814),

49653 (−14)

Igfbp4
81890
(+1793)

Igsf23
47518
(+17363)

Igsf3
22210
(+116958)

Ikzf3
81720 (+54048), 81695 (+84313),

81694 (+85638)

Il10
4615
(+44544)

Il12rb2
42316
(+108091)

Il17ra
44862
(+936)

Il17rb
96635 (+3413), 96620 (+14837),

96618 (+15373), 96616 (+16673)

Il18bp
51697
(+46961)

Il1b
15056
(−14340)

Il1r2
940
(−134444)

Il27ra
57012
(+14948)

Il2rb
103482
(+14779)

Il3
77479
(−20829)

Il4ra
52817
(−3779)

Il5
77316
(+6031)

Il6st
95165
(−35432)

Il9
93058 (−24983), 93057 (−23585),

93052 (−20355)

Ilkap
3574
(+18050)

Impa2
118523
(+636)

Impad1
24770
(+13)

Impdh2
65993
(−38603)

Ina
122943 (−251931), 122950 (−195318),

122952 (−177170), 122973 (−149168),

122974 (−145742)

Ino80d
2242
(+542)

Inpp5f
53303
(−55480)

Insig1
32869
(+22708)

Insl6
121578 (+46396), 121574 (+54008)

Ipmk
70775 (+28402), 70778 (+50474)

Ipo5
100185
(+502)

Irf1
77316
(−43189)

Irf2
55572
(+1483)

Irf2bp2
59689
(−251373)

Irf2bpl
88145
(−1861)

Irf5
40369
(+2288)

Irf8
59005
(−57705)

Irg1
99792 (−64111), 99800 (−17450)

Irgm2
77812
(+24317)

Irs2
54431 (+2720), 54430 (+3209),

54412 (+13167), 54409 (+15922),

54395 (+25939), 54392 (+26890),

54391 (+27336)

Isoc1
118067
(+447)

Itgb6
12140
(−207690)

Itgb7
105484
(+25965)

Itm2b
99150 (−9066), 99147 (−3533),

99111 (+51159)

Itpk1
88842
(−14920)

Itpr1
44086
(+269568)

Jag1
15557 (−120478), 15549 (−809),

15546 (+1095)

Jak1
27833
(−17)

Jak2
121560 (−95), 121561 (+302),

121574 (+19520), 121578 (+27132)

Jarid2
92015
(−407126)

Jdp2
88020
(+61682)

Jhdm1d
41029 (−94938), 41011 (−72)

Kank1
121440
(−183546)

Kansl1l
2407
(−147)

Katnal1
39588
(+332021)

Kcmf1
42567 (−499), 42566 (+25),

42565 (+367)

Kcna3
22612
(+472)

Kcne3
51444
(−131)

Kcnh8
113837 (−818874), 113868 (−542871)

Kcnj1
60770
(+115752)

Kcnj6
110004
(+276777)

Kcnma1
96208
(+903827)

Kctd17
103470
(+19270)

Kctd6
95628
(+1300)

Kdm3b
116851 (+431), 116852 (+2473),

116857 (+7844)

Kdm4c
27209
(−20699)

Kdm6b
78729
(−4447)

Keap1
60310 (+115), 60291 (+71892)

Kif17
30714
(+7178)

Kif19a
83423
(+21190)

Kif26a
89642
(−5802)

Kif2a
94848
(−923)

Kif5c
11711
(+481)

Kif6
113665
(+566802)

Kif7
50303
(−7294)

Klc1
89594
(−35954)

Klf12
99695 (+368034), 99659 (+849636)

Klf13
49412
(−207)

Klf2
56504
(+12278)

Klf3
34286 (−572640), 34353 (−310798),

34404 (+822)

Klf4
26546 (−869), 26523 (+180431)

Klf5
99659 (+1469), 99695 (+483071)

Klhl21
31683
(+1063)

Klhl8
35989
(+54811)

Kpna1
107624 (+1322), 107629 (+44826)

Kpna2
83029 (−28708), 83018 (+41831)

Krt78
105445
(−34026)

Krt8
105445
(+16029)

Krtcap3
33058
(+28026)

Ktn1
97330 (−14028), 97338 (+194382)

Lama5
18143
(+32)

Lamc2
5895
(+128917)

Lamp1
54534
(−26737)

Lamtor3
23887
(−47225)

Larp1
77733 (−97195), 77768 (+37550)

Lat2
38417
(−15385)

Lbx1
122683
(+10538)

Lca5l
110097
(+20922)

Lclat1
114705
(+145556)

Lcor
122388
(+576)

Ldb2
33897
(+561237)

Lemd2
111467
(−107)

Lemd3
73830
(+927)

Leng9
46780
(−1782)

Letmd1
105248 (−25263), 105253 (−5300)

Lgi1
122221
(+13854)

Lhx1
80333
(−268690)

Lif
74657
(+3830)

Lin7c
14062
(+411)

Lmf1
111246 (+21258), 111252 (+34439),

111255 (+85013)

Lmnb1
118014
(+29740)

Lmo4
24211 (−205486), 24155 (−2793),

24153 (−1725), 24150 (+889),

24149 (+1765), 24147 (+3258),

24144 (+5129), 24142 (+7286),

24131 (+13736), 24130 (+14242),

24128 (+15590), 24127 (+16663),

24126 (+17072), 24125 (+18086)

Lmod3
43727
(−194445)

Lnp
12768
(+471)

Lnx2
39457
(+16405)

Loh12cr1
45819
(+75948)

Lonrf1
55383
(−4)

Lonrf2
805
(+285323)

Lor
21511 (+1717), 21510 (+2165)

Lpgat1
8284
(+464)

Lrcol1
36472 (+22926), 36476 (+63135)

Lrmp
46389
(+3035)

Lrp1
74252 (−794), 74249 (+16455)

Lrp4
13391
(+69658)

Lrrc10b
120668
(+7492)

Lrrc2
66212
(+2240)

Lrrc32
51231
(+40383)

Lrrc57
14481
(+30809)

Lrrc58
107709
(+887)

Lrrc66
34960
(+140008)

Lrrc8d
36142 (+8427), 36153 (+46311)

Ly9
7277
(−29588)

Lysmd4
49598
(−109910)

Macf1
29056 (+19024), 29005 (+268582)

Maea
33256
(+9055)

Maf
58532
(−118)

Maff
103656 (+2419), 103662 (+12261)

Malt1
118405
(+1547)

Mamdc2
121354
(+166230)

Mamstr
48875
(−4528)

Mania
69821
(+4)

Man1a2
22140
(−675)

Man1c1
30172
(−67)

Man2a2
50460 (−16223), 50456 (−14171),

50455 (−13799), 50454 (−13250),

50453 (−12910), 50452 (−12753),

50451 (−12092), 50450 (−11400),

50449 (−11206), 50448 (−9973)

Map10
59584
(−98526)

Map1lc3b
59096 (+1038), 59103 (+60158)

Map2k1
63217
(−75)

Map2k4
78453
(+107684)

Map3k1
95112 (−540), 95085 (+121370)

Map3k2
116627
(+1911)

Map3k5
68241
(+900)

Map4k2
120306 (−1076), 120308 (+1268)

Map4k4
915 (−134), 940 (+49411)

Map4k5
86615 (−19769), 86614 (+53)

Map7
68275
(+1082)

Mapk1ip1
53575
(−828)

Mapkapk2
4615
(+33178)

Mapkapk3
65772
(+19593)

Mapkapk5
37480
(−95)

March3
118014
(+187995)

March6
101327
(−506)

March7
12041 (−84824), 12049 (+42)

Marcksl1
29469
(+949)

Mark3
89562
(−32636)

Marveld3
58185
(+44668)

Mast4
94716 (−32555), 94665 (+428265)

Mbnl1
20008
(+601)

Mbp
119422 (+14106), 119423 (+14523),

119445 (+59382)

Mc2r
118689
(+81820)

Mc5r
118689
(+9828)

Mcl1
21722
(+7631)

Mdh1
75607
(+1009)

Mdm1
73612
(−76882)

Med13l
37242
(+612)

Med4
99150
(−115712)

Mef2d
21115
(+644)

Melk
26105
(−29539)

Men1
120302
(−3564)

Mepce
38809
(−156)

Mesdc1
50843
(−125)

Mettl10
53449
(+28123)

Mettl16
79203
(−30716)

Mettl24
69164 (+366), 69165 (+22162)

Mex3b
50809
(−199)

Mfrp
61466
(−12672)

Mfsd10
33368
(+62141)

Mfsd11
83775
(−678)

Mfsd6
1512
(+88255)

Mgat4a
733
(+11370)

Micall1
103630
(+620)

Micu2
97974
(−55)

Mier1
27986 (−860), 27987 (+3749),

27988 (+4220)

Mier3
95085
(+1445)

Mill2
47298
(−132)

Mipep
98100
(−13341)

Mknk2
71510
(+10472)

Mkrn1
41056
(−30741)

Mlec
36999 (+5705), 36997 (+6549)

Mll3
32849
(−438)

Mllt10
9619
(−183)

Mmp17
38256
(−59734)

Mmp25
110999 (−6441), 110998 (+170),

110989 (+27995), 110988 (+30995)

Moap1
88842
(+23871)

Mob3c
28500
(−76)

Mocs3
17631
(+735)

Mon2
74044 (+43), 74030 (+88635),

74029 (+90447)

Mphosph8
97874
(+108549)

Mpnd
113949
(+9331)

Mppe1
118502 (+109798), 118501 (+111665)

Mpzl1
6848
(−62436)

Mrc2
82684
(−107737)

Mrm1
80333
(+24810)

Mroh8
16473
(+464)

Mrpl33
33086
(−17537)

Mrpl37
28122
(+154342)

Mrps28
18339 (+155758), 18337 (+157002),

18336 (+157655), 18327 (+246541)

Mrps30
95552
(+744546)

Mrps6
109692
(+820)

Msh4
24619
(+56369)

Msh5
112655
(−3631)

Msi2
80831 (−3064), 80785 (+239094),

80781 (+267279)

Msl1
81805
(+1013)

Msr1
55412
(+648947)

Msrb3
73819
(+3108)

Mta2
120549
(−612)

Mtap
27519
(−197508)

Mtfr2
68324
(+222696)

Mthfd1l
67491 (+127020), 67489 (+138855)

Mtif3
39457
(−96396)

Mum1
71419
(+937)

Mvb12b
11028
(+614)

Mxi1
123123
(−168982)

Myl1
2425
(+48506)

Myo15b
83614
(+8007)

Myo16
54365
(+448115)

Myo1b
1362
(+406084)

Myo1d
80090
(−549)

Myo3a
9799
(−263540)

Myo3b
12482 (+30601), 12488 (+86092)

Myo6
64602
(−97125)

Myocd
78453
(−410672)

Myrf
120653
(−3634)

Mzt1
99645
(−161)

N4bp2l1
39720
(−102)

Naa30
97385
(+1325)

Naa35
93206
(+17980)

Naa38
40132 (−6505), 40133 (−6210)

Nab2
74271
(−4874)

Nabp1
1362 (−31445), 1347 (+3206),

1346 (+3563), 1339 (+10951),

1337 (+12296)

Naif1
10806
(+670)

Nampt
85562 (−439641), 85585 (+6826)

Nans
26257
(−36591)

Narg2
63742 (−222953), 63759 (−107593),

63817 (−69288), 63869 (−33432),

63870 (−33081), 63907 (−6717)

Ncald
101658
(−140149)

Ncl
3160
(+19830)

Ncoa2
203 (−123050), 189 (+471),

143 (+145545)

Ncoa3
17173
(−34)

Ncoa7
68827
(−1045)

Ncor2
38164 (−88490), 38112 (+126405)

Ndfip1
117249
(−70244)

Neb
11801
(−47856)

Nedd9
91818
(−149000)

Neu1
112614
(+21355)

Neu3
51388
(+5929)

Neurog3
70274
(+63332)

Nfatc1
119336 (−765), 119335 (−25),

119331 (+1767)

Nfib
27226
(−343716)

Nfic
71769 (−43535), 71756 (−3515)

Nfil3
92779 (+6211), 92778 (+7421)

Nfix
57140
(−39849)

Nfrkb
60677
(−104490)

Nfyc
28876
(−60)

Ngef
3284
(+14467)

Nicn1
65954
(−9866)

Nin
86642 (−14498), 86641 (−9211)

Ninj1
92417 (+123), 92418 (+593)

Nipal3
30382
(+55196)

Nipbl
100765
(−125422)

Nkd2
93562
(−60291)

Nkx1-1
33269
(−62408)

Nkx2-3
122507
(−4177)

Nlrp3
77927
(−37)

Nmnat2
5876 (−52901), 5877 (−52214),

5895 (+102429)

Nmrk1
121181 (−121), 121182 (+7790)

Nmrk2
71679 (+3599), 71677 (+6795),

71676 (+7685), 71675 (+9183)

Nmt2
8430
(+341)

Nnat
16518
(−58614)

Nnmt
61919
(−225200)

Noxa1
9946
(−16266)

Npas2
840
(+6)

Npas3
86148
(−419499)

Npepps
81456
(−130)

Npnt
23426
(+202765)

Npr3
100906
(−77875)

Nr1d2
95816
(+21)

Nr2f6
56367
(−855)

Nr3c1
117442 (−30157), 117432 (−3721),

117431 (−3215)

Nr3c2
56618 (−2672), 56619 (−2409)

Nr4a2
11870 (−9177), 11862 (+390)

Nr4a3
26393 (−1791), 26394 (−740)

Nradd
66161
(+87335)

Nrarp
9946
(−69343)

Nrd1
28336 (+89538), 28338 (+93959)

Nrde2
88525
(−25568)

Nrf1
40455
(+664)

Nrxn3
88222
(−328191)

Nsa2
94336
(−28)

Nsd1
92905 (+2065), 92906 (+2582)

Nsun7
34654
(+261652)

Nt5e
64886
(−1479)

Ntng2
10352
(−4396)

Nubpl
86106
(+406812)

Nudtl5
99189
(−4528)

Nudt3
111537
(−4139)

Nudt4
72576
(−1570)

Numa1
51697
(+1351)

Nup214
10714
(+64422)

Nxn
79460
(−483)

Nxph4
74249
(−70134)

Nxt1
15804
(−150289)

Nyx
123996
(+54639)

Oaz1
71578
(−199)

Obfc1
123043 (+8852), 123038 (+17995)

Oit3
69980
(−73397)

Olfr1025-ps1
12768
(−11341550)

Olfr1026
12768
(−11346893)

Olfr1028
12768
(−11374688)

Olfr1029
12768
(−11398836)

Olfr1030
12768
(−11402935)

Olfr1031
12768
(−11415442)

Olfr1257
13263
(+2674)

Olfr1258
13263
(−46201)

Onecut3
71468
(+1239)

Opa1
107075 (+429421), 107077 (+430444)

Orc5
32592
(−865670)

Os9
74129
(+17004)

Osbpl9
28338 (+107658), 28336 (+112079)

Osgin2
25353
(−55624)

Ostf1
121181
(−40)

Otp
94137
(−83187)

Otud1
9775
(+367)

Otx2
97366
(+203347)

Pabpc1
101499 (−30086), 101493 (−3265)

Pabpc1l
16906
(+28587)

Pabpc2
117442
(−256108)

Pacs1
120075
(−1118)

Pacs2
89771
(+472)

Pafah1b1
79203 (−15444), 79202 (+140)

Paip1
95569 (+314), 95570 (+615),

95571 (+1098)

Pak6
14312
(+39507)

Palld
55887
(−31267)

Palm3
57012
(+6156)

Pan3
39498
(+1002)

Pank2
15172
(+68245)

Pank4
31859
(−2031)

Papd5
57336
(+591)

Papss1
23417
(−12087)

Pard3
59733
(−16060)

Pard3b
2158 (−624872), 2206 (+28)

Pard6b
17613
(+36384)

Parp10
103173
(+12390)

Parp11
45379
(−19399)

Parp8
95446 (−8556), 95445 (−346)

Paxbp1
109563 (−12109), 109560 (−1197),

109552 (+8500), 109547 (+23840),

109546 (+24577)

Pbrm1
96799
(−2745)

Pbx3
11042
(+128)

Pcgf5
122084
(−60357)

Pcid2
54533 (−930), 54532 (−209)

Pcif1
16997
(+58)

Pcnp
108588
(+54708)

Pcsk7
61721
(+316)

Pdcd1
3767
(−22417)

Pdcd1lg2
121613
(−24822)

Pdcd6ip
66317
(−10997)

Pde1a
13070
(−56965)

Pde2a
51617
(+27883)

Pde4a
60291
(+1726)

Pde4b
27900 (+256628), 27930 (+331977)

Pde4d
95003
(−131542)

Pde4d
95003
(+241176)

Pde7b
68324
(+154563)

Pde8a
50717
(+416)

Pdgfc
20738
(+992)

Pdia2
111319
(+58270)

Pdia3
14532
(−20)

Pdia6
85112
(+1127)

Pdik1l
30118
(+49)

Pdk1
12603
(+475)

Pdlim1
122249
(−896)

Pdp1
25239
(+145801)

Pdpr
58245 (+523), 58250 (+54872)

Pds5b
39740
(+702)

Pdzd8
123565
(−4459)

Peli2
97338
(−262731)

Perp
68055 (+153951), 68056 (+154497),

68057 (+155057)

Pex14
31332 (+197966), 31331 (+198891)

Pfn2
19802 (−944), 19801 (−466)

Pglyrp3
21510 (+66394), 21511 (+66842)

Phc1
45048
(−1727)

Phc2
29324
(+39206)

Phlda3
5051
(+54)

Phlpp2
58185
(+48889)

Phtf1
22360
(−52395)

Phtf2
32420
(−179)

Pi4k2b
34011
(+630)

Pias3
21922
(+427)

Piezo1
59218
(+67340)

Pigc
6592
(−81136)

Pik3cg
85555
(−130998)

Pik3r1
94561
(+113330)

Pip4k2a
9753
(−174)

Pithd1
30464
(−1011)

Pitpnb
36533 (−231979), 36559 (−122701)

Pitpnm2
38003
(+28698)

Pkd1l2
58648
(+11508)

Pkd2l2
116815
(−28663)

Pkn2
24090
(−134887)

Pkn3
10442
(−12286)

Pla2g4a
5619
(−48882)

Plac8
35784
(+2556)

Plagl2
16076
(−59)

Plat
54756
(−187)

Plau
96057
(+34)

Plaur
47593 (−2903), 47596 (+4)

Plcb3
120378
(−1133)

Plcg1
16730
(+335)

Plcg2
58689 (−210838), 58731 (−118993)

Plec
103173
(−24708)

Plekha5
46075
(+456)

Plekhg2
47965
(−5307)

Plekhh1
87278
(+459)

Plekhm1
82468
(+15792)

Plin1
50303
(+11296)

Plxdc1
81591 (+27312), 81585 (+40284),

81584 (+43072)

Plxnc1
72508
(−235773)

Plxnd1
44522 (−115), 44519 (+1041)

Pm20d2
25623
(−27)

Pmepa1
17946
(+476)

Pnn
86417
(−75)

Pofut1
16076
(−48)

Polb
54726
(+3094)

Pold4
119913
(−16241)

Poldip3
104152
(−1096)

Pole4
42654
(+15842)

Poll
122720
(+22826)

Polr2h
106684
(+57)

Pou3f1
29080
(+14219)

Ppa1
70251
(+6332)

Ppa2
23520
(+539)

Ppapdc1b
54918
(−116322)

Pparg
44451
(+97334)

Ppcdc
62437
(+171826)

Ppfibp1
46595
(+58796)

Ppif
96375
(+66615)

Ppm1a
86799
(+3024)

Ppm1h
74029 (+307276), 74030 (+309088)

Ppp1ca
119903
(+4247)

Ppp1r12a
73132 (−510), 73134 (+669)

Ppp1r14a
48134
(−187)

Ppp1r14b
120378
(−4126)

Ppp1r16b
16651
(+16059)

Ppp1r3e
97682
(+250)

Ppp2r2d
53575
(+729)

Ppp2r3a
65524
(−42)

Ppp2r4
10486 (+54130), 10487 (+56003)

Ppp2r5a
8260
(−29040)

Ppp2r5c
89392
(+5918)

Ppp2r5e
87037
(−176)

Ppp3cb
95993
(−22)

Ppp4r4
88963
(+346)

Ppt2
112553
(−3977)

Pqlc1
119255
(+37)

Prc1
50419
(+20142)

Prdm10
60677
(+1164)

Prdm14
143
(−101375)

Prdx6
6475
(+970)

Prdx6b
13070
(−327074)

Prep
69597
(+560)

Prex1
17353
(−5038)

Prickle1
104667
(−638)

Prima1
88929
(−92083)

Prkaca
57002
(+3913)

Prkar2b
85532
(−53)

Prkca
83155 (−34331), 83141 (+94168)

Prkcd
96760
(−17079)

Prkcq
9170
(−798219)

Prl5a1
91022
(+615460)

Prnp
15232
(−6793)

Prob1
116952
(−7)

Prom2
14868
(−17994)

Prorsd1
75834
(+10327)

Prpf40b
105111
(+1112)

Prph2
113406
(+98704)

Prr3
112891
(−13614)

Prrt1
112553
(+1592)

Prrt3
44295
(+7416)

Prx
47882
(−8285)

Psd2
117023
(−88516)

Psma7
18124 (−707), 18123 (+20)

Psmg1
110080 (−49954), 110063 (+103009),

110057 (+136537)

Pspc1
97874
(+1519)

Ptbp1
71278
(+1530)

Pten
121936
(+684)

Ptges3
74305
(−24)

Ptgfrn
22177 (+54821), 22175 (+57585)

Ptgr2
87840 (−64475), 87848 (−23700)

Ptgs2
5619
(−89952)

Ptms
45188
(+171)

Ptp4a1
390
(+331)

Ptplad1
63283
(+79)

Ptpn13
35938
(+170453)

Ptpn9
62411 (+738), 62412 (+1208)

Pura
117070 (+317), 117071 (+5386)

Pvr
47518
(−12220)

Pxdc1
91387
(+254453)

Qrich1
65993
(+4753)

Rab10
84594
(+2236)

Rab24
92906 (+109616), 92905 (+110133)

Rab28
33804
(−183)

Rab2a
24960
(+1793)

Rab38
50985
(+882843)

Rab43
43275
(−907)

Rab44
111820 (−20915), 111823 (+21485)

Rab8b
63609
(−11084)

Rabgef1
38316
(+16990)

Rad23b
26523
(+1992)

Rad51d
80158
(+3859)

Rad9a
119903
(+5198)

Raf1
44483
(−669)

Rai1
77976
(+730)

Rala
90485
(−3990)

Ramp1
3533
(+123)

Ramp3
75018 (+9079), 75023 (+15541),

75025 (+16769), 75026 (+17020),

75027 (+17434), 75031 (+20155),

75032 (+20818), 75034 (+22027),

75035 (+22987), 75049 (+110517)

Ran
38238
(+776)

Rap1a
22468
(+75108)

Rap1b
73612
(−218970)

Rap1gap
30624
(+27324)

Rapgef2
20671 (−191284), 20629 (−98692),

20551 (+196603)

Rara
81848
(−4304)

Rasa2
65312 (−89770), 65290 (−2363)

Rasl11a
39436
(+59155)

Rassf3
73873
(+57045)

Rassf5
4675
(+492)

Rb1
99111
(−8290)

Rbbp6
52715
(+464)

Rbbp8
116231
(+163382)

Rbfa
119244
(+2024)

Rbm11
108872
(+778)

Rbm34
59733
(−76917)

Rbm5
65869
(+35101)

Rbms1
12162 (−1), 12140 (+81791)

Rbpms
55137
(−788)

Rcan3
30382
(−5574)

Rcc2
30908
(+702)

Rccd1
50419
(+9832)

Rcor3
8336
(−217)

Rcsd1
6848
(+11117)

Rdh10
247 (−387), 248 (+30)

Rdx
62088
(+876)

Rec8
97760
(+956)

Reep2
116852 (−61177), 116857 (−55806)

Reep5
116815 (−7345), 116813 (−2450)

Reps1
67985 (+73), 67986 (+305),

67999 (+23015)

Ret
44674 (−724), 44673 (+339)

Retsat
42515
(+16916)

Rev3l
69021
(−212)

Rffl
80158
(−57724)

Rft1
96760
(−29459)

Rftn1
113665
(+8700)

Rgl1
5838
(+173487)

Rgma
49777
(+131502)

Rgr
97043
(+15575)

Rgs10
53290
(−434)

Rgs13
5522
(+99924)

Rgs2
5522 (−73287), 5496 (+150165)

Rgs9
83193
(+44060)

Rhd
30206
(+15092)

Rif1
11768
(−45)

Rilpl2
38051
(+32125)

Rims4
16883
(−33260)

Ring1
112423
(−3364)

Ripk2
25353
(+94135)

Rit1
21226
(−29516)

Rlf
28924
(−28)

Rmi1
93154
(−201)

Rnf125
116416
(+25939)

Rnf138
116416
(−13765)

Rnf139
102254
(+186)

Rnf144b
92344
(+16)

Rnf145
76366
(+25370)

Rnf157
83698
(−609)

Rnf170
54986
(+2004)

Rnf19a
101467
(−88)

Rnf2
5695
(−119)

Rnf207
31780
(+5576)

Rnf214
61721
(−8)

Rnf24
15175 (+317), 15172 (+22136)

Rnf38
26105
(−103729)

Rnf8
111924
(+23273)

Rnpepl1
3692
(−171)

Rock2
85082
(+519)

Rora
63742 (+521167), 63759 (+636527),

63817 (+674832), 63869 (+710688),

63870 (+711039), 63907 (+737403)

Rpl10-ps3
61961
(−131851)

Rpl24
108588
(+8756)

Rpl31
854
(+371)

Rpl7
248 (−1142), 247 (−725)

Rplp0
37078
(−3141)

Rplp1
62921 (+2901), 62920 (+3692),

62917 (+4724), 62916 (+5288),

62915 (+5758), 62914 (+6164),

62913 (+6370), 62872 (+250317),

62826 (+534160)

Rpn2
16473
(+26)

Rpp40
91520
(+164127)

Rprd1b
16547 (+86109), 16548 (+86471),

16549 (+87150), 16550 (+87504),

16552 (+88442), 16556 (+93960),

16562 (+104572)

Rps19bp1
103787
(+5063)

Rps27l
63609
(−15297)

Rps3a3
94939
(−279792)

Rps6
27362
(+106659)

Rps6ka1
30025
(+70169)

Rpsa-ps10
24417
(+743762)

Rptor
84216
(+57598)

Rragd
25608
(+621)

Rrbp1
15677
(+952)

Rrm2b
101658
(+28521)

Rsbn1
22360
(+1595)

Rsph3b
110510
(+121115)

Rtfdc1
17813
(−43747)

Rtkn2
70620
(+147747)

Rtn2
47399
(+26038)

Rtp3
66212
(+35928)

Rttn
119641
(−71444)

Rufy2
70376 (+253), 70377 (+4056)

Runx3
30310
(+45441)

Rwdd3
23032
(+66637)

Rxfp2
39703
(+99894)

Rxra
10259
(+87889)

Rxrb
112423
(−3768)

Ryk
65563 (+477), 65564 (+25239)

Ryr3
14107 (+517345), 14105 (+520339)

Sacs
98127
(+100510)

Samd1
57002
(−20781)

Samd8
96140
(+919)

Samsn1
108901
(+47387)

Sap30l
77726 (−94), 77728 (+924)

Sar1a
70251
(−25426)

Satb1
113868 (−350216), 113837 (−74213),

113821 (−1140), 113808 (+18721),

113774 (+96215), 113760 (+579153)

Sbf2
52021
(+360795)

Sbno1
38035
(+14928)

Sc4mol
55896
(+26057)

Sc5d
61379
(+55503)

Scaf4
109507
(−57)

Scaf8
110250
(+810)

Scarb1
38164
(+73390)

Scgb1a1
120568
(+96696)

Scgb3a1
76772 (+42423), 76773 (+43347)

Scmh1
28836
(−41314)

Scn1b
48351
(−649)

Scrib
103134
(+54429)

Scrt1
103244
(−181)

Scyl1
120211 (−62390), 120195 (−25399),

120194 (−25011), 120193 (−23741)

Sdf4
32044
(+169)

Sdk1
39081
(+2254)

Sdpr
1337 (+176977), 1339 (+178322),

1346 (+185710), 1347 (+186067)

Sec63
69363
(+929)

Sel1l
88339
(−974456)

Sema3f
65869
(−25426)

Sema4b
50367
(−10470)

Sema4f
42699
(+59703)

Senp6
64602
(+1003)

11-Sep
35502
(−53227)

Serac1
110446
(+15877)

Serbp1
42316
(+1118)

Serpinb9
91329
(+4649)

Serpinb9b
91329
(−19517)

Serpine1
38686
(−19494)

Serpine2
2814
(+181)

Sertad1
47882
(+4129)

Sesn1
69276
(+78050)

Sesn3
60018
(−378139)

Set
10442
(+4445)

Setd2
66161
(+4461)

Setd8
38051
(+6311)

Sf1
120308
(−21262)

Sf3a2
71557
(−41907)

Sfmbt2
9170
(+1713)

Sfswap
38256
(+23249)

Sgcg
98127
(+19523)

Sgip1
27900 (−248732), 27930 (−173383)

Sgms2
23417
(−167794)

Sgpl1
70180
(−3)

Sgsm2
79223
(−276)

Sh2b1
52911
(−214)

Sh3bp4
3447 (+582), 3452 (+60183)

Sh3gl1
113949
(+18103)

Sh3glb1
24270
(−3317)

Sh3pxd2a
123043 (−63757), 123038 (−54614)

Sidt2
61728 (+8273), 61727 (+9003)

Sik1
112165 (−18291), 112161 (−1229),

112160 (−965), 112151 (+7693),

112146 (+12714)

Sik2
62043
(−1190)

Sik3
61750 (+7609), 61758 (+34449)

Sin3a
62412
(−80223)

Sipa1l2
59584 (−78582), 59572 (+50248)

Sirt1
70409 (−38624), 70408 (−35)

Skap1
81310
(−428)

Ski
31919
(−11534)

Skida1
9612
(+1067)

Skil
19058 (−30), 19059 (+656)

Slain1
99870
(+1213)

Slamf7
7277
(+12020)

Slc10a1
87621
(+21243)

Slc10a6
35938
(+33758)

Slc11a2
105253 (−40679), 105248 (−20716),

105245 (−29)

Slc12a2
118056
(+678)

Slc15a1
100268
(+106144)

Slc16al2
122056
(+84995)

Slc19a2
6727
(−57720)

Slc1a3
100765
(+140879)

Slc22a23
91387
(−53036)

Slc24a2
27375
(+346730)

Slc25a24
22851 (+102), 22852 (+695),

22864 (+92667)

Slc25a25
10806
(+295)

Slc25a29
89340
(+40960)

Slc25a33
31435
(−1499)

Slc25a38
66901
(−11566)

Slc25a39
82324
(−560)

Slc25a40
32279
(+760)

Slc25a51
26167
(+65046)

Slc2a1
28757
(+3131)

Slc30a5
94561
(−821460)

Slc35d1
27988 (+95306), 27987 (+95777)

Slc35e2
31982
(+38)

Slc35g1
122221
(−117344)

Slc36a4
60168
(+431)

Slc37a3
41029
(+75980)

Slc44a1
26454
(−244195)

Slc44a3
23051
(+89823)

Slc48a1
104891
(+2592)

Slc4a1ap
33086
(+69405)

Slc4a7
95742
(+707)

Slc5a11
52743
(+3598)

Slc5a3
109692
(+768)

Slc5a9
28421
(+181516)

Slc9a6
124597
(+955)

Slco2a1
65564
(−148333)

Slco2b1
51375
(+47555)

Slco3a1
49870
(+129921)

Slco6c1
3835 (−532818), 3834 (−532675)

Slk
123068
(+71028)

Slmap
96421
(+7102)

Slx4ip
15546
(+223381)

Smad2
119091 (+646), 119092 (+846)

Smad7
119004
(+1752)

Smagp
105272
(−579)

Smap1
357
(−120)

Smarcd1
105165
(+3556)

Smarcd2
82787
(−85)

Smc5
121354
(−8215)

Smco4
60145
(−11267)

Smcr7
78054
(−457)

Smg7
5877 (−24719), 5876 (−24032)

Smim6
83614
(−42398)

Smndc1
123212 (−106471), 123192 (−33655)

Smox
15196
(+359)

Smurf2
83018
(−37240)

Snap23
14481
(+10809)

Snapc1
86991 (−55322), 87004 (−21114)

Snrk
67120
(+47524)

Snta1
16174
(+4)

Sntb2
58060
(+35196)

Snx13
85658
(+501)

Snx18
95299 (−11973), 95292 (+9124)

Snx21
16974 (−69), 16975 (+53)

Socs1
105995
(+137187)

Socs2
72539
(+787)

Socs6
119641
(−6024)

Socs7
81476
(+42685)

Sod1
109479 (−78332), 109486 (−43058)

Son
109657
(+10154)

Sorl1
61379 (−84500), 61371 (+15767),

61351 (+89969)

Sos1
115026
(+88596)

Sowaha
77217
(+497)

Sowahb
35502
(−40345)

Sox4
91022
(+195769)

Sp1
105535
(+4952)

Sp3
12650
(+695)

Sp5
12482 (−348024), 12488 (−292533)

Spata1
24342
(−1135)

Spata32
82414
(+149)

Spata6
28421
(+1418)

Spcs3
55701 (+2673), 55698 (+5359)

Spen
31030
(−2508)

Spesp1
62956
(+159429)

Spin1
92500 (−32777), 92501 (−32496)

Spint2
48133
(+122)

Spocd1
29573
(+3870)

Sppl3
36940 (+781), 36984 (+80302)

Sprtn
59554
(+24271)

Spry1
19283
(+1036)

Sptan1
10432 (−225), 10433 (+364)

Sptb
87136
(−58)

Sptssa
86265 (+13677), 86220 (+197437),

86191 (+343295)

Spty2d1
49029
(+856)

Spz1
94012
(+21260)

Src
16518
(+83052)

Srek1
94716
(+407444)

Srgap2
4704
(+2058)

Sri
32270
(−75693)

Srl
105732
(+67177)

Srp9
7901
(−33383)

Srrd
36674
(−353)

Srrm2
111037
(+1676)

Srsf1
80725
(−44396)

Srsf11
24665
(+73470)

Srsf2
83775
(−78)

Srsf3
111808
(+41609)

Srsf5
87621
(+1156)

Srsf6
16763
(+595)

Srsf9
37039
(−97)

SS18l1
18123 (−96), 18124 (+631)

Ssbp3
28098 (−75463), 28122 (+1056)

Ssh1
36823 (−162), 36822 (+81)

Ssh2
79577
(+377)

St8sia1
46249 (−29498), 46225 (+93996)

St8sia2
49870
(−411011)

Stard3nl
90590 (−122873), 90502 (+441517)

Stard7
14832
(+392)

Stat5b
82066
(−580)

Steap4
32270
(+20362)

Stim1
51748 (−511), 51751 (+800)

Stk11
71377
(−3940)

Stk24
100268 (−19775), 100267 (−133),

100220 (+69191)

Stk32c
53587
(+58546)

Strn4
47217
(+763)

Stt3b
66527
(−77227)

Stx6
6118
(+64512)

Stxbp1
10923
(−204)

Styx
97184
(+31620)

Sub1
100906
(+12509)

Sucla2
99189 (+105), 99191 (+732)

Suclg2
43638
(+104114)

Suco
6592
(−11389)

Sugt1
99559 (−57900), 99572 (−45883)

Sun2
103718 (−64), 103713 (+18894)

Supt3
113142
(−67054)

Surf4
10173
(+1108)

Suv420h1
119808
(+1495)

Svil
115988 (−266575), 116001 (+561)

Swap70
52021
(+32424)

Syne2
87054
(−663)

Synj1
109552 (−24735), 109547 (−9395),

109546 (−8658), 109542 (−900)

Synj2
110446
(+122461)

Synm
49648 (−152271), 49644 (−84308)

Synrg
80305
(+91726)

Syp
123715
(−20097)

Sypl
85585
(−126730)

Syt7
120668
(+60865)

Sytl2
51073
(−35514)

Tacc2
53339
(+69095)

Tacr1
42654
(+234612)

Taf12
29746
(−12705)

Taf3
9123
(+56069)

Taf4a
18116
(−258)

Taf6l
120516
(−35)

Tagln
61728 (−10646), 61727 (−9916)

Tapt1
33897 (−11864), 33895 (−531)

Taz
124857
(−4582)

Tbc1d1
34286 (+71432), 34353 (+333274)

Tbc1d24
111095
(−1361)

Tbc1d30
73854
(+182)

Tbc1d4
99761
(−28576)

Tbc1d5
113808 (−634640), 113774 (−557146),

113760 (−74208)

Tbc1d7
91913
(−90882)

Tbc1d8
860
(+24)

Tbca
94137
(+3497)

Tbck
23426
(+63134)

Tbl1xr1
18782
(+780)

Tbx2
80411
(+12220)

Tcam1
82787
(−3691)

Tceb2
111037
(+24116)

Tec
34840
(+37194)

Tesc
37174
(−25429)

Tet3
42809
(+84897)

Tex15
55096
(−52853)

Tex261
42856
(−161)

Tex35
6281
(−272244)

Tfpi
13183 (+3691), 13182 (+3976)

Tgfa
43009
(+303)

Tgfbr1
26376
(+15733)

Tgif2
16415
(+541)

Tgm2
16591 (−36814), 16562 (+13143),

16556 (+23755), 16552 (+29273),

16550 (+30211), 16549 (+30565),

16548 (+31244), 16547 (+31606)

Tgoln1
42515
(+1609)

Th
53960
(−68183)

Thap4
3743
(+11)

Theg
71233
(−8129)

Thsd7b
4482 (−666922), 4514 (−533828),

4522 (−529998), 4523 (−529727),

4524 (−529372)

Tiam1
109486 (−202985), 109479 (−167711)

Tigit
107917
(−33745)

Tiparp
20165
(+815)

Tjp2
121391
(+49738)

Tle1
27208
(−927)

Tle3
62815 (−2742), 62826 (+6993),

62872 (+290836), 62913 (+534783),

62914 (+534989), 62915 (+535395),

62916 (+535865), 62917 (+536429),

62920 (+537461), 62921 (+538252)

Tle4
120977
(−115648)

Tlk1
12531
(−207)

Tlk2
82684
(+3382)

Tlx1
122683
(+76037)

Tm2d2
54836
(−57)

Tm9sf2
100431
(+4902)

Tmc6
83908
(+125007)

Tmcc3
72440
(+496)

Tmco6
117139
(−561)

Tmem11
78066
(+351)

Tmem120b
37767
(+740)

Tmem135
50985
(+25671)

Tmem154
20874
(+44741)

Tmem17
75639
(+179897)

Tmem170b
91818
(−103034)

Tmem182
1095
(+69596)

Tmem184b
103662 (+43501), 103656 (+53343)

Tmem186
105900
(−28976)

Tmem194b
1512
(+8502)

Tmem201
31428
(−107)

Tmem216
120678
(+428)

Tmem242
110309 (+442831), 110308 (+443448)

Tmem245
26623
(−59)

Tmem247
115543 (−137919), 115556 (−128155)

Tmem248
38316
(−15593)

Tmem260
97366
(+17784)

Tmem41b
51971
(+17404)

Tmem50a
30206
(+35396)

Tmem57
30205
(−567)

Tmem60
32420
(+112)

Tmem81
4789
(+14687)

Tmprss1bnl
35235
(−61297)

Tmprss11e
35235
(+8156)

Tmprss6
103482 (−11653), 103470 (+20736)

Tmtc2
73080
(+1404)

Tnfaip3
68057 (+15282), 68056 (+15842),

68055 (+16388)

Tnfaip8
117724 (−50699), 117768 (+21466)

Tnfrsf18
32059 (+2189), 32063 (+5402),

32064 (+5620)

Tnfrsf22
54048
(−17478)

Tnfrsf23
54048
(+18733)

Tnfrsf9
31621
(+27948)

Tnfsf18
6556
(+256190)

Tnk2
107387
(−105)

Tnpo3
40369
(+80974)

Tnrc6c
83908
(+1343)

Tns4
81890
(+46269)

Tob1
81004
(+861)

Tom1
56600
(−9846)

Tomm20
59689
(+101014)

Tomm20l
86714
(−94355)

Tomm34
16906
(+17065)

Topbp1
65583
(+27755)

Tor2a
10911
(+441)

Tox
24897
(−367573)

Tpbpb
93257
(−28248)

Tpgs2
116568
(−3204)

Tpm4
56458
(+586)

Tprn
9991
(+426)

Trabd
104517
(+540)

Traf3
89524
(+520)

Traf7
111131
(−129)

Trak1
67019 (+401), 67038 (+130913)

Tram1
203
(+92731)

Trappc6b
86416
(+45)

Trim24
40884
(+809)

Trim27
90679
(+766)

Trim56
38686
(+24441)

Trim62
29353
(+981)

Trim67
59545
(+275)

Trim8
122870
(−126)

Trio
101264
(−271)

Triobp
103611
(+55451)

Trip12
3015
(+128913)

Trip13
93562
(+29845)

Trp53bp2
7955
(+301)

Trp53rk
17353
(−74897)

Trpc5
125856
(+161947)

Trps1
101872
(+126712)

Trpv4
36872 (+41615), 36866 (+74750)

Trub1
123480 (−84122), 123482 (−77558),

123483 (−61665)

Tsc22d3
125744
(+804)

Tsen2
44451
(−25264)

Tshz3
48520
(+225)

Tspan15
70274
(+34804)

Tsr1
79223
(−742)

Tssc4
53979
(−13289)

Tsx
125302
(+54744)

Ttbk2
14493
(+44287)

Ttc28
36533 (+218982), 36559 (+328260)

Ttc39c
116303
(+1018)

Ttc7
115690
(+1074)

Ttc8
88427 (−144), 88439 (+304663)

Ttll10
32064 (+19033), 32063 (+19251),

32059 (+22464)

Ttyh1
46765
(−99)

Tusc3
55412
(+10164)

Txk
34840
(−78485)

Txndc9
787
(−1289)

Tysnd1
70260
(+19793)

Ubac2
100311
(+980)

Ubash3b
61371 (−950468), 61351 (−876266)

Ubc
38193
(−1553)

Ube2cbp
64864
(−2614)

Ube2d2a
116975 (+511), 116976 (+2479)

Ube2d3
23606
(−13)

Ube2e3
12923
(+98)

Ube2g1
79054
(+1214)

Ube2j1
25612
(+2319)

Ube2q2
62227 (+881), 62228 (+1225)

Ube2r2
25868
(+481)

Ube2w
260 (+152), 259 (+741)

Ubl3
39588
(−43838)

Ubr2
113406
(+1369)

Ubr4
30840
(+1015)

Ubtd2
76012
(+604)

Ubtf
82317 (−358), 82315 (+787)

Ubxn2a
84772
(−27)

Uchl5
5496
(+76718)

Ugcg
26785 (−29084), 26789 (+499)

Unc119b
36999 (−17499), 36997 (−16655)

Unc50
733
(+94695)

Ung
36832
(+543)

Upb1
70877 (−86418), 70883 (−80187),

70902 (+5611)

Upf1
56168
(−190)

Upp1
75060
(+493)

Urod
28624
(−1546)

Usf2
48316 (−723), 48315 (−74)

Usp12
39417
(−4644)

Usp2
61466
(+22149)

Usp24
28031
(+386)

Usp25
109179
(+13715)

Usp6nl
8724
(−29985)

Ust
67653
(−157)

Utp11l
29080
(+21736)

Uts2
31621
(−48959)

Uvrag
51281
(+45806)

Uvssa
33256
(−34076)

Vamp3
31641
(−112)

Vamp4
6635
(−265)

Vapa
114343
(−101)

Vav1
114193
(+37064)

Vav3
22864
(−124837)

Vcan
93897
(+3019)

Vdac3
54723
(−278)

Vegfc
55698 (+447106), 55701 (+449792)

Vmn1r238
115859
(−139049)

Vps37a
55454
(+374)

Vps37b
37972 (−1709), 37949 (+14471),

37932 (+26504), 37931 (+27023),

37930 (+27413), 37928 (+28274),

37927 (+28595), 37926 (+28828),

37925 (+29082), 37924 (+29477),

37923 (+29725), 37922 (+30144),

37920 (+31237), 37919 (+32388),

37917 (+33041), 37916 (+33496)

Vps4a
58060
(−60275)

Wasf2
29863
(−117969)

Wbp1l
122915
(+20979)

Wbp4
99572 (−60540), 99559 (−48523)

Wbscr16
38338
(+9939)

Wdpcp
75607
(−1051)

Wdr1
33618
(−790)

Wdr45b
84519 (+64447), 84514 (+93917)

Wdr5b
107624 (−56553), 107629 (−13049)

Wdr78
27986
(−479)

Whsc1
33295
(−157)

Whsc1l1
54918
(+1458)

Wnk1
44805
(−98)

Wnk2
92404
(+173146)

Wnt11
51281
(+256493)

Wrb
110097
(+25928)

Wtap
110718
(−370)

Wwc2
55643
(−570)

Xirp1
66851
(+38654)

Xpo1
75722
(−106066)

Yes1
33210
(+491)

Ypel2
80575
(+131414)

Ypel4
13213
(−14)

Ypel5
114620
(+824)

Yrdc
29118
(+641)

Ythdc2
117607
(+304)

Ythdf2
29742
(+79)

Ywhab
16883 (−43017), 16892 (+558)

Ywhaz
101552 (+875), 101499 (+155479)

Yy1
89338 (−65), 89340 (+1950)

Zbed3
94171
(+4424)

Zbtb1
87097 (−174), 87099 (+941)

Zbtb16
61919
(+5592)

Zbtb18
7544
(−2614)

Zbtb2
67471 (+1332), 67472 (+3075)

Zbtb22
112386
(−5283)

Zbtb42
89682
(+9819)

Zbtb46
18258
(−73)

Zbtb48
31683
(+17795)

Zc3h12c
62110 (−20186), 62107 (−791),

62106 (−314)

Zc3h15
13095
(+494)

Zc3havl
40909 (+27399), 40906 (+32662)

Zc3hav1l
40909 (−27945), 40906 (−22682),

40892 (+734)

Zcchc13
125302
(−161375)

Zcchc14
59103 (+2275), 59096 (+61395)

Zcchc24
96387 (−61680), 96375 (+8071)

Zcwpw1
38809
(−979)

Zdhhc18
29977 (−86), 29975 (+564)

Zdhhc21
27226
(+10649)

Zdhhc23
107937 (−2159), 107936 (−1337)

Zeb1
116031 (+1533), 116032 (+2026)

Zeb2
11509
(+186082)

Zfand5
121232
(+698)

Zfp125
85161
(−175098)

Zfp217
17789 (−232354), 17788 (−231852)

Zfp236
119492 (−118181), 119445 (+158190),

119423 (+203049), 119422 (+203466)

Zfp318
113325
(+849)

Zfp326
36181
(+99189)

Zfp335
17007
(+423)

Zfp358
54189
(+373)

Zfp36
47965
(+1715)

Zfp36l2
115317 (+1085), 115302 (+26083)

Zfp395
98430 (−14868), 98438 (+326)

Zfp428
47605
(−21664)

Zfp507
48500
(−25)

Zfp516
119492 (−99964), 119527 (+37277)

Zfp532
118405
(−147720)

Zfp574
47683
(−4022)

Zfp583
46932
(+42918)

Zfp592
50689 (−119), 50690 (+214),

50691 (+1004)

Zfp64
17691
(−25855)

Zfp651
67072
(+353)

Zfp652
81208
(+862)

Zfp661
14868
(+27633)

Zfp664
38091
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Zkscan16
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Zmym5
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Zmynd8
17112 (+211141), 17111 (+224936)

Zscan10
110988 (+13418), 110989 (+16418)

Zswim6
94888
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Zxdc
43436
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Zyg11b
28253
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Zyx
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Various modifications and variations of the described methods, pharmaceutical compositions, and kits of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific embodiments, it will be understood that it is capable of further modifications and that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the art are intended to be within the scope of the invention. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure come within known customary practice within the art to which the invention pertains and may be applied to the essential features herein before set forth.

COMPOSITIONS AND METHODS FOR MODULATING CGRP SIGNALING TO REGULATE INTESTINAL INNATE LYMPHOID CELLS

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