METHODS FOR IDENTIFYING ANTI-CANCER COMPOUNDS

BACKGROUND OF THE INVENTION

The initiation of cap-dependent translation involves ˜13 tightly controlled protein factors (reviewed in (Jackson et al., 2010)). Among these, eIF4E binds the mRNA cap structure and interacts with a scaffold (eIF4G) and the eIF4A RNA helicase (a DEAD box protein also known as DDX2). During initiation these and other factors form the eIF4F complex and together with the 40S ribosomal unit proceed to a transcript's 5′UTR for a translation start site. The eIF4A RNA helicase is directly involved in scanning and recent studies have defined co-factors and the molecular mechanics of its helicase activity (Marintchev, 2009, 2013; Parsyan et al., 2011; Svitkin, 2001). However, the precise mRNA features that necessitate the eIF4A helicase action are not known.

The activation of protein translation contributes to malignant transformation. For example, activation of the RAS, ERK, and AKT signaling pathways stimulates cap-dependent translation (reviewed in (Blagden and Willis, 2011; D'Ambrogio et al., 2013; Guertin and Sabatini, 2007). Moreover, the rate limiting eIF4E translation factor is expressed at high levels in many cancers and can transform rodent fibroblasts and promote tumor development in vivo (Lazaris-Karatzas et al., 1990; Ruggero et al., 2004; Wendel et al., 2004). Accordingly, cap-dependent translation is an emerging target for cancer therapies (see recent review by (Blagden and Willis, 2011). Notably, three distinct natural compounds target the eIF4A helicase and these are silvestrol isolated from plants in the Malaysian rainforest (Cencic, 2009), pateamine A found in marine sponges off the coast of New Zealand (Northcote et al., 1991), and hippuristanol which is produced by pacific corals (Li et al., 2009b). These compounds show promising preclinical activity against different cancers (Bordeleau et al., 2005; Bordeleau et al., 2006; Cencic et al., 2007; Schatz et al., 2011; Tsumuraya et al., 2011a). Other strategies to inhibit translation include rapamycin and mTORC1 kinase inhibitors (Hsieh et al., 2012; Thoreen et al., 2009), inhibitors of the eIF4E kinase MNK1/2 (Furic et al., 2010; Ueda et al., 2004; Wendel et al., 2007), a peptide (4EGI-1) that interferes with the eIF4E-eIF4G interaction (Moerke et al., 2007), and the anti-viral ribavirin that may bind eIF4E directly (Kentsis et al., 2004; Yan et al., 2005).

The recently developed transcriptome-scale ribosome footprinting technology greatly facilitates the study of protein translation. Briefly, the technology is based on the identification of ribosome-protected RNA fragments in relation to total transcript levels using deep sequencing (Ingolia et al., 2009). The technology has been applied to explore translational effects in various biological contexts, and perhaps the most relevant to this study are reports of the translational effects of mTORC1 inhibition on mRNAs harboring TOP- and TOP-like sequences (Hsieh et al., 2012; Thoreen et al., 2012).

BRIEF DESCRIPTION OF THE INVENTION

In one embodiment, a method is provided for identifying an agent capable of modulating cap-dependent mRNA translation. The method comprises comparing translation efficiency in the presence and absence of the agent in an in-vitro or in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs. eIF4A refers to eIF4A1 or eIF4A2, and RNA helicases include, but are not limited to, eIF4A1, eIF4A2, DHX9 or DHX36. The modulation of translation in the presence of the agent indicates the agent as capable of modulating cap-dependent mRNA translation. In one embodiment, modulating is decreasing, suppressing or inhibiting cap-dependent mRNA translation. In one embodiment, the agent stabilizes the binding of eIF4A to the eIF4A-dependent translation-controlling motif of the mRNA. In one embodiment, the eIF4A-mRNA complex stabilizing motif of the mRNA is located in the 5′ UTR.

In one embodiment, the eIF4A-dependent translation-controlling motif comprises a G-quadruplex structure. In one embodiment, the G-quadruplex structure comprises a (GGC/A)₄motif. In one embodiment, the (GGC/A)₄motif comprises GGCGGCGGCGGC (SEQ ID NO:1). In one embodiment, the eIF4A-dependent translation-controlling motif comprises a sequence selected from SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 or SEQ ID NO:10. In one embodiment, the eIF4A-dependent translation-controlling motif comprises a sequence selected from among SEQ ID NO:10 to SEQ ID NO:62. In one embodiment, the eIF4A-dependent translation-controlling motif is at least one sequence selected from SEQ ID NO:1 or from among SEQ ID NO:4 to SEQ ID NO:62.

In one embodiment of the methods described herein, the mRNA encodes a transcription factor. In one embodiment, the mRNA encodes an oncogene. In other embodiments, the mRNA encodes NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2. In other embodiments, the mRNA is from a gene selected from Table 3A. In other embodiments, the mRNA is from a gene selected from Table 3B. In other embodiments, the mRNA is from a gene selected from Table 3C.

In one embodiment of the method, the agent suppresses the growth of cancer cells in vitro or in vivo. In one embodiment, the agent interferes with eIF4A activity. In one embodiment, the agent increases eIF4A activity. In one embodiment, the agent inhibits eIF4A helicase activity. In one embodiment, the agent increases eIF4A helicase activity. In one embodiment, the agent promotes the stabilizing the binding of eIF4A with an eIF4A-dependent translation-controlling motif. In one embodiment, the agent does not trigger feedback activation of Akt.

In one embodiment, the modulation of translation in the foregoing method is measured by a fluorescence reporter assay. In one embodiment, the assay comprises renilla luciferase expression.

In one embodiment, a method is provided for identifying an agent that modulates eIF4A activity, the method comprising comparing translation efficiency in the presence and absence of the agent in an in-vitro or in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein the increase or decrease in translation efficiency in the presence of the agent indicates the agent as capable of increasing or decreasing eIF4A activity.

In one embodiment, a method is provided for identifying an agent that inhibits eIF4A activity, the method comprising comparing translation efficiency in the presence and absence of the agent in an in-vitro or in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein a decrease in translation efficiency in the presence of the agent indicates the agent as capable of inhibiting eIF4A activity.

In one embodiment, a method is provided for determining whether an mRNA sequence comprises at least one eIF4A-dependent translation-controlling motif, the method comprising comparing translation efficiency in the presence and absence of an agent that inhibits eIF4A activity in an in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein a decrease in translation efficiency in the presence of the agent indicates the mRNA sequence possesses at least one eIF4A-dependent translation-controlling motif.

In one embodiment, a method is provided for determining whether a cancer or tumor is susceptible to an agent that inhibits eIF4A activity, the method comprising identifying the presence of at least one eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor, wherein the presence of the at least one eIF4A-dependent translation-controlling motif indicates susceptibility of the cancer or tumor to the agent. In one embodiment, the level of expression of MYC is not predictive of the susceptibility of a cancer or tumor to an agent that inhibits eIF4A activity.

In one embodiment, a method for preventing, treating or intervening in the recurrence of a cancer in a subject is provided. The method comprises administering to the subject an agent that blocks eIF4a helicase activity, thereby preventing, treating or intervening in the recurrence of the cancer. In one embodiment, the agent that blocks eIF4A helicase inhibits the translation of an oncogenic mRNA. In one embodiment, the oncogenic mRNA comprises an eIF4A-dependent translation-controlling motif. In one embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In one embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the oncogenic mRNA comprises a G-quadruplex motif. In one embodiment, the oncogenic mRNA is from an oncogene, which by way of non-limiting example is selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2.

In the foregoing embodiments, the cancer is, by way of non-limiting examples, T-cell acute lymphoblastic leukemia, small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, neuroblastoma and pancreatic cancer. In one embodiment the subject has cancer. In one embodiment, the subject is at risk for developing cancer. In one embodiment, the subject is in remission from cancer. In other embodiments, the cancer is transformed follicular lymphoma, mantel cell lymphoma, breast cancer, ovarian cancer, hepatocellular carcinoma, and non-small cell lung cancer, as well as gastric cancer, Ewing sarcoma and lung adenocarcinoma.

In one embodiment, a method is provided for preventing, treating or intervening in the recurrence of a cancer in a subject having an eIF4A dependent cancer. The method comprises administering to the subject an agent that blocks eIF4a helicase activity, thereby preventing, treating or intervening in the recurrence of the cancer. In one embodiment, the agent that blocks eIF4A helicase inhibits the translation of an oncogenic mRNA. In one embodiment, the oncogenic mRNA comprises an eIF4A-dependent translation-controlling motif. In one embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In one embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the oncogenic mRNA comprises a G-quadruplex motif. In one embodiment, the oncogenic mRNA is from an oncogene. In one embodiment, the oncogene is selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2.

In another embodiment, a method is provided for inhibiting in a subject the translation of an oncogene that comprises an eIF4A-dependent translation-controlling motif. The method comprises administering to the subject an agent that blocks eIF4a helicase, thereby inhibiting translation of the oncogene. In one embodiment, translation of the oncogene causes cancer in the subject. In another embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In this embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the mRNA of the oncogene comprises a G-quadruplex motif. In one embodiment, the oncogene is selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2.

In one embodiment, a method for inhibiting in a subject eIF4A dependent mRNA translation is provided. The method comprises administering to the subject an agent that blocks eIF4a helicase, thereby inhibiting mRNA translation. In one embodiment, the mRNA translation causes cancer in the subject. In one embodiment, the mRNA comprises an eIF4A-dependent translation-controlling motif. In one embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In one embodiment, the mRNA encodes an oncogenic protein. In one embodiment, the oncogenic protein is encoded by an oncogene selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2.

In one embodiment, a method for preventing in a subject the translation of an mRNA comprising an eIF4A-dependent translation-controlling motif. The method comprises administering to the subject an agent that blocks eIF4a helicase activity, thereby inhibiting translation of the mRNA. In one embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In one embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the mRNA is from an oncogene selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2. In one embodiment, the translation of the mRNA causes cancer.

In any of the foregoing embodiments, the agent blocks the activity of eIF4A helicase. In any of the foregoing embodiments, the agent blocks the translation of an mRNA comprising an eIF4A-dependent translation-controlling motif. In any of the foregoing embodiments, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In any of the foregoing embodiments, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62.

Non-limiting examples of aforementioned agents include a rocaglamide, such as silvestrol, CR-31-B, or an analogue or derivative thereof. In other embodiments, the agent is hippuristanol, pateamine A, or an analogue or derivative thereof.

U.S. Patent Application Ser. No. 61/912,420, filed Dec. 5, 2013, is incorporated herein by reference in its entirety.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows that translational activation contributes to T-ALL pathogenesis and maintenance;

FIG. 2 shows that silvestrol blocks cap-dependent translation and has single-agent activity against T-ALL;

FIG. 3 shows that transcriptome-scale ribosome footprinting can be used to define silvestrol's effects on translation;

FIG. 4 shows that silvestrol alters the distribution of ribosomes across many mRNAs;

FIG. 5 shows that many cancer genes are differentially affected by silvestrol;

FIG. 6 shows the validation of selected silvestrol targets;

FIG. 7 is a diagram depicting an eIF4A dependent mechanism of translational control;

FIG. 8 shows the PI3K pathway and translational activation in T-ALL;

FIG. 9 shows testing silvestrol and the synthetic analogue CR-31-B in T-ALL;

FIG. 10 shows ribosome profiling quality control data and effects on translation;

FIG. 11 shows analysis of genes with differential ribosomal distribution;

FIG. 12 shows gene ontology analysis of silvestrol sensitive genes;

FIG. 13 illustrates exploring the relative contribution of MYC and other silvestrol targets in T-ALL;

FIG. 14 illustrates a FRET-based assay for measuring the effect of RNA helicases on G-G-quadruplex unwinding, screening proteins that can unwind G-quadruplexes and identify small molecules that stabilize the G-quadruplex structure;

FIG. 15 shows the sensitivity of several small cell lung cancer lines to silvestrol;

FIG. 16 shows the sensitivity of several renal cell carcinoma cell lines to silvestrol;

FIG. 17 shows the sensitivity to silvestrol of a number of cancer cell lines;

FIG. 18 shows that the sensitivity of cancer cell lines to silvestrol is not predicted by MYC expression;

FIG. 19 shows activity of hippuristanol and panteamine A in the reporter assay;

FIG. 20 shows in vitro data on silvestrol on a number of lung cancer cell lines and key target proteins;

FIG. 21 shows the effect of silvestrol on lung cancer cells in the presence and absence of serum, with and without MG-132, and the effect on key target proteins;

FIG. 22 shows transcripts of KRAS, and the presence of G-quadruplex structures;

FIG. 23 compares the G-quadruplex structures in NRAS and KRAS;

FIG. 24 shows the effect of silvestrol on KRAS protein levels in PANC1 cells and the effect of various compounds on PANC1 and MiaPaca2 cells;

FIG. 25 shows the in vivo activity of silvestrol on MiaPaca2 xenografts;

FIG. 26 shows the effect in individual animals xenografted with H82 small cell lung cancer cells and treated with silvestrol, etoposide or both; and

FIG. 27 shows a summary of in vivo data for two dose levels of silvestrol and the effects on key target proteins.

DETAILED DESCRIPTION OF THE INVENTION

A mechanism of translational control has been identified that is characterized by a requirement for eIF4A/DDX2 RNA helicase activity and underlies the anticancer effects of silvestrol and related compounds. eIF4A refers to eIF4A1 or eIF4A2, and RNA helicases include, but are not limited to, eIF4A1, eIF4A2, DHX9 or DHX36. In one embodiment, activation of cap-dependent translation contributes to T-cell leukemia (T-ALL) development and maintenance. Accordingly, inhibition of the translation initiation factor eIF4A with silvestrol produces powerful therapeutic effects. By using transcriptome-scale ribosome footprinting on silvestrol-treated T-ALL cells to identify silvestrol-sensitive transcripts, the features of eIF4A-dependent translation embodied herein were identified. These features include, in one embodiment, a long 5′UTR and a 12-mer sequence motif that encodes a guanine quartet (GGC)₄. RNA folding algorithms pinpoint the (GGC)₄motif as a common site of RNA G-quadruplex structures within the 5′UTR. In T-ALL these structures mark highly silvestrol-sensitive transcripts that include key oncogenes and transcription factors and contribute to the drug's anti-leukemic action. Hence, the eIF4A-dependent translation of G-quadruplex containing transcripts is shown as a gene-selective and therapeutically targetable mechanism of translational control.

Thus, in one embodiment, a method for identifying an agent capable of modulating cap-dependent mRNA translation is provided, the method comprising comparing translation efficiency in the presence and absence of the agent in an in-vitro or in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein the modulation of translation in the presence of the agent indicates the agent as capable of modulating cap-dependent mRNA translation. In some embodiments, modulating is decreasing, suppressing or inhibiting cap-dependent mRNA translation.

eIF4A-dependent translation-controlling motifs are typically present in the 5′ UTR of the mRNA. In certain embodiments, the eIF4A-dependent translation-controlling motif comprises a G-quadruplex structure. In some embodiments, the G-quadruplex structure is a (GGC/A)₄motif (i.e., four occurrences of (G, G, C or A), each occurrence independently selected from either GGC or GGA). In some embodiments, the (GGC/A)₄motif is GGCGGCGGCGGC (SEQ ID NO:1). In some embodiments, the eIF4A-dependent translation-controlling motif comprises GGGAC (SEQ ID NO:2) motif or GGGCC (SEQ ID NO:3). In other embodiments the eIF4A-dependent translation-controlling motif comprises SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 or SEQ ID NO:10. In other embodiments, the eIF4A-dependent translation-controlling motif comprises a sequence selected from among SEQ ID NO:10 to SEQ ID NO:62. In other embodiments, the eIF4A-dependent translation-controlling motif is at least one sequence selected from SEQ ID NO:1 or from SEQ ID NO:4 to SEQ ID NO:62.

The mRNA may have one or more eIF4A-dependent translation-controlling motifs. In one embodiment, the eIF4A-dependent translation-controlling motif is at least one (GGC/A)₄motif. In another embodiment, the eIF4A-dependent translation-controlling motif is at least one GGGAC (SEQ ID NO:2) motif. In another embodiment, the eIF4A-dependent translation-controlling motif is at least one GGGCC (SEQ ID NO:3) motif. In another embodiment, the eIF4A-dependent translation-controlling motif is at least one 12-mer motif. In other embodiments, the mRNA may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, or more eIF4A-dependent translation-controlling motifs. In another embodiment, each eIF4A-dependent translation-controlling motif is independently selected from among SEQ ID NO:1 through and including SEQ ID NO:62.

In one embodiment, an agent identified by the methods of the invention may interfere with eIF4A activity. In one embodiment, the agent may increase eIF4A activity. In one embodiment, the agent may inhibit eIF4A helicase activity. In another embodiment, the agent may increase eIF4A helicase activity. In another embodiment, the agent can promote the stabilizing the binding of eIF4A with an eIF4A-dependent translation-controlling motif.

In another embodiment, the agent does not trigger feedback activation of Akt.

In another embodiment, the mRNA encodes a transcription factor. In another embodiment, the mRNA encodes an oncogene. In another embodiment, the mRNA encodes NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2. In another embodiment the mRNA is from a gene selected from Table 3A. In another embodiment, the mRNA is from a gene selected from Table 3B. In another embodiment, the mRNA is from a gene selected from Table 3C.

The agent identified by the methods herein may be used to treat cancer. In one embodiment, the cancer is a result of the overexpression an oncogene or transcription factor. The oncogene or transcription factor may be selected from those described herein, such as but not limited to NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2, or any described in Table 3A, 3B or 3C.

Cancer includes cancerous and precancerous conditions, including, for example, premalignant and malignant hyperproliferative diseases such as cancers of the breast, ovary, germ cell, skin, prostate, colon, bladder, cervix, uterus, stomach, lung, esophagus, blood and lymphatic system, larynx, oral cavity, as well as metaplasias, dysplasias, neoplasias, leukoplakias and papillomas of the mucous membranes, and in the treatment of Kaposi's sarcoma. These are also referred to herein as dysproliferative diseases or dysproliferation. Non-limiting examples of other cancers, tumors, malignancies, neoplasms, and other dysproliferative diseases that can be treated according to the invention include leukemias, such as myeloid and lymphocytic leukemias, lymphomas, myeloproliferative diseases, and solid tumors, such as but not limited to sarcomas and carcinomas such as fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, and retinoblastoma.

In one embodiment, the compounds and uses embodied herein are directed to small cell lung cancer. In one embodiment, the compounds and uses embodied herein are directed to renal cancers. In one embodiment, the compounds and uses embodied herein are directed to neuroblastoma. In one embodiment, the compounds and uses embodied herein are directed to pancreatic cancers.

In one embodiment the agent suppresses the growth of cancer cells in vitro or in vivo.

The method of carrying out the translation assay using an in-vitro or in-vivo assay described herein may be accomplished by any of a number of methods know in the art. In one embodiment, the modulation of translation is measured by a fluorescence reporter assay. In one embodiment, the fluorescence reporter assay comprises renilla luciferase expression.

As mentioned above, certain mRNAs have longer 5′ UTRs and the eIF4A-dependent translation-controlling motif is present in the 5′ UTR. In one embodiment, the eIF4A-dependent translation-controlling motif comprises a 12-mer and the mRNA is from a gene selected from Table 3A. In another embodiment, the eIF4A-dependent translation-controlling motif comprises a 9-mer and the mRNA is from a gene selected from Table 3B. In another embodiment, eIF4A-dependent translation-controlling motif comprises a (GGC)₄motif and the mRNA is from a gene selected from Table 3C.

In another embodiment, a method for identifying an agent that modulates eIF4A activity is provided. The method comprises comparing translation efficiency in the presence and absence of the agent in an in-vitro or in-vivo translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs. An increase or decrease in translation efficiency in the presence of the agent indicates the agent as capable of increasing or decreasing eIF4A activity, respectively. The in-vitro or in-vivo translation system may be one from among those described here. The mRNA may be among those described herein. The eIF4A-dependent translation-controlling motifs may be among those described herein.

In another embodiment, a method is provided for identifying an agent that inhibits eIF4A activity, the method comprising comparing translation efficiency in the presence and absence of the agent in an in-vitro translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein a decrease in translation efficiency in the presence of the agent indicates the agent as capable of inhibiting eIF4A activity. The in-vitro or in-vivo translation system may be one from among those described here. The mRNA may be among those described herein. The eIF4A-dependent translation-controlling motifs may be among those described herein.

In another embodiment, a method is described for determining whether an mRNA sequence comprises at least one eIF4A-dependent translation-controlling motif. In this method, translation efficiency is compared in the presence and absence of an agent that inhibits eIF4A activity in an in-vitro translation system comprising eIF4A and an mRNA having one or more eIF4A-dependent translation-controlling motifs, wherein a decrease in translation efficiency in the presence of the agent indicates the mRNA sequence possesses at least one eIF4A-dependent translation-controlling motif. By way of non-limiting example, the agent is selected from among silvestrol(methyl(1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-R1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate), pateamine A ((3S,6Z,8E,11S,15R,17S)-15-amino-3-[(1E,3E,5E)-7-(dimethylamino)-2,5-dimethylhepta-1,3,5-trienyl]-9,11,17-trimethyl-4,12-dioxa-20-thia-21-azabicyclo[16.2.1]henicosa-1(21),6,8,18-tetraene-5,13-dione), hippuristanol, (±)-CR-31-B, among other rocaglamide((1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide) derivatives.

Methods are also provided for determining whether a cancer or tumor is susceptible to an agent that inhibits eIF4A activity. In one embodiment, the method comprising identifying the presence of at least one eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor, wherein the presence of the at least one eIF4A-dependent translation-controlling motif indicates susceptibility of the cancer or tumor to the agent. In other embodiments, the eIF4A-dependent translation-controlling motifs are among those described herein above. In one embodiment, the presence of MYC is not predictive of the susceptibility of a cancer or tumor to an agent that inhibits eIF4A activity.

In another embodiment, a method for determining whether a patient having cancer or a tumor will respond to treatment with an eIF4A inhibitor is provided comprising the steps of 1) obtaining a sample of the cancer or tumor from the patient; and 2) identifying the presence of at least one eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor, wherein the presence of the at least one eIF4A-dependent translation-controlling motif indicates that the patient will respond to the treatment. In the foregoing embodiments, identifying the presence of at least one eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor can be performed by comparing translation efficiency in the presence and absence of an eIF4A inhibitor agent in an in-vitro or in-vivo translation system comprising eIF4A and mRNA from the cancer or tumor, wherein a decrease in translation efficiency in the presence of the agent indicates the presence of an eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor. In another embodiment, identifying the presence of at least one eIF4A-dependent translation-controlling motif in mRNA from the cancer or tumor can be performed by identifying a G-quadruplex motif in at least one oncogene in the cancer or tumor. In certain embodiments, the motif is selected from among those described in SEQ ID NO:1 and in any one of SEQ ID NO:4-62. In certain embodiments, the expression of MYC is not correlated with responsiveness or sensitivity of a patient's cancer or tumor to an agent that inhibits eIF4A activity.

In another embodiment, a method is provided for determining whether a patient having cancer or a tumor will respond to treatment with an eIF4A inhibitor comprising the steps of 1) obtaining a sample of the cancer or tumor from the patient; and 2) identifying the presence of at least one oncogene in the cancer or tumor described in Table 3A, 3B or 3C herein, wherein the presence of said at least one oncogene indicates that the patient will respond to the treatment. In one embodiment, the presence or expression of MYC is not correlated with responsiveness or sensitivity to the treatment.

Furthermore, in other embodiments, methods to determine the level of expression of eIF4E, eIF4A, eIF4G, or eIF4B, and presence of the eIF4F complex indicate sensitivity to silvestrol and other eIF4A inhibitors, and such methods carried out in any format will be useful or determining if a tumor or patient's cancer will be sensitive to silvestrol. In another embodiment, measuring the expression of Mdr1/p-glycoprotein, a resistance marker for silvestrol, indicates the eIF4A inhibitors may be less effective and require a different dosing regimen, such as but not limited to dose level and dosing frequency. In another embodiment, expression of other helicases, e.g. DHX9 and DHX36, may causes resistance to silvestrol and thus useful in identifying cancers or tumors that may not be sensitive to silvestrol, to guide the chemotherapeutic regimen to the optimal benefit of the patient.

In one embodiment, methods are provided for 1) measuring the effect of known RNA helicases such as eIF4A, DHX9 or DHX36 on G-quadruplex unwinding; 2) investigating the effect of other cofactors/inhibitors required for eIF4A activity; 3) a screening method to identify other proteins that can unwind G-quadruplexes; and 4) identifying and establishing the effect of small molecules that stabilize the G-quadruplex structure. These methods among others may be achieved by use of a fluorescence resonance energy transfer (FRET)-based assay utilizing an oligonucleotide comprising a G-quadruplex labeled with a fluorophore at the 5′ or 3′ end of the oligonucleotide, and a fluorescence quencher at the other. In one non-limiting example, a FRET-labeled GC-quadruplex is 5′-UAGAA ACUAC GGCGG CGGCG GAAUC GUAGA (SEQ ID NO:65) and a mutant oligonucleotide without the G-quadruplex is UAGACCCUGCAACGUCAGCGUAGUCGUAGC (SEQ ID NO:66). The 5′-end is labeled with fluorophore FAM and quencher BHQ1 on the 3′end. When folded, the labeled G-quadruplex RNA oligonucleotide will exhibit minimum baseline fluorescence. Addition of specific RNA helicase such as EIF4A with ATP and/or small molecules results in unwinding and increase in fluorescence signal measured in real time. The aforementioned FRET-labeled G-quadruplex containing oligonucleotide is merely one example and those comprising other G-quadruplexes such as but not limited to SEQ ID NOS:1-64, and in particular SEQ ID NOS:1-62 may be employed for this purpose, with other fluorophores and quencher pairs well known in the art.

This assay can therefore be used for the aforementioned purpose as well as various other purposes such as but not limited to 1) measuring the effect of known RNA helicases such as eIF4A, DHX9 or DHX36 on G-quadruplex unwinding; 2) investigating the effect of other cofactors/inhibitors required for eIF4A activity; 3) a screening method to identify other proteins that can unwind G-quadruplexes; and 4) identifying and establishing the effect of small molecules that stabilize the G-quadruplex structure.

In addition to the various embodiments described above, methods are also provided for treating a subject having cancer, and for preventing cancer in a subject at risk or recurrence in a patient in remission. Based on the findings herein that translation of oncogenes comprising an eIF4A-dependent translation-controlling motifs is dependent on eIF4A helicase activity, blocking eIF4A helicase activity is a means to prevent oncogenic protein production and prevent oncogenesis. As described herein, numerous cancer-related genes including oncogenes and transcription factors are dependent on eIF4A for translation. Heretofore, the role of eIF4A was unclear but the present studies show, inter alia, that specific motifs on oncogenic mRNAs depend on eIF4A for translation, thus blocking eIF4A helicase is a heretofore unappreciated anti-cancer mechanism. Use of agents that target eIF4A dependent translation can thus stop translation of oncogenic mRNA sequences.

In further embodiments, methods are provided for reducing or preventing recurrence of cancer in a patient in remission or otherwise considered cured. In these embodiments, the cancer is any among those described herein among others, and by way of non-limiting examples, T-cell acute lymphoblastic leukemia, small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, neuroblastoma and pancreatic cancer. In other embodiments, the cancer is transformed follicular lymphoma, mantel cell lymphoma, breast cancer, ovarian cancer, hepatocellular carcinoma, and non-small cell lung cancer, as well as gastric cancer, Ewing sarcoma and lung adenocarcinoma. In one embodiment the subject has cancer. Other cancers are described in FIG. 17 are included herein, as well as the cell lines representative of such cancers. In one embodiment, the subject is at risk for developing cancer. In one embodiment, the subject is in remission from cancer.

Among these methods, administering to the subject an agent that blocks eIF4a helicase activity prevents, treats or intervenes in the recurrence of the cancer. In one embodiment, a method for preventing, treating or intervening in the recurrence of a cancer in a subject is provided. The method comprises administering to the subject an agent that blocks eIF4a helicase activity, thereby preventing, treating or intervening in the recurrence of the cancer. In one embodiment, the agent that blocks eIF4A helicase inhibits the translation of an oncogenic mRNA. In one embodiment, the oncogenic mRNA comprises an eIF4A-dependent translation-controlling motif. In one embodiment, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In one embodiment, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62. In one embodiment, the oncogenic mRNA comprises a G-quadruplex motif. In one embodiment, the oncogenic mRNA is from an oncogene, which by way of non-limiting example is selected from among Tables 3A, 3B and 3C. In one embodiment, the oncogene is NOTCH1, BCL11B, MYC, CDK6, RUNX1, BCL2 or MDM2.

In any of these embodiments, the agent blocks the activity of eIF4A helicase. In any of the foregoing embodiments, the agent blocks the translation of an mRNA comprising an eIF4A-dependent translation-controlling motif. In any of the foregoing embodiments, the eIF4A-dependent translation-controlling motif is a G-quadruplex motif. In any of the foregoing embodiments, the eIF4A-dependent translation-controlling motif is selected from among SEQ ID NOs:1-62.

Non-limiting examples of aforementioned agents include a rocaglamide, such as silvestrol, CR-31-B, or any active analogue or derivative thereof. In other embodiments, the agent is hippuristanol, pateamine A, or any active analogue or derivative thereof. Other examples of suitable agents include those described in WO2011/140334 (based on PCT/US2011/035351).

Hallmark features are described here of eIF4A-dependent translation and defines specific 5′UTR elements that confer a requirement for that RNA helicase. The key features are longer 5′UTRs, a 12-mer (GGC)₄motif, and related 9-mer variant motifs. Importantly, the 12-mer and 9-mer motifs precisely localize to between 53% and 65% of all predicted RNA G-quadruplex structures (depending on the analysis tool). The 9-mer sequences require neighboring nucleotides to complete the structure as the minimal number is 12 nucleotides, and it was frequently observed that more than 12 nucleotides contribute to the G-quadruplex. Moreover, most of the remaining G-quadruplexes are based on highly similar sequence elements. On the other hand IRES mRNAs are somewhat protected, while TOP, TOP-like, or PRTE elements do not appear to influence the eIF4A requirement. This is distinct from mTORC1 inhibition, which affects a different set of transcripts marked by TOP and TOP-like elements (Thoreen et al., 2012). These findings identify sequence motifs that represent translational control elements encoded in the 5′UTR of several hundred transcripts and that confer a requirement for eIF4A RNA helicase action.

RNA G-quadruplex structures are typically made from at least two stacks of four guanosines exhibiting non-Watson-Crick interactions (e.g. hydrogen bonds) and connected by one or more linker nucleotides (reviewed in (Bugaut and Balasubramanian, 2012)). In the examples herein, the linker is most often a cytosine and less frequently an adenosine. There is variation in the exact structural composition and sequence requirement as our examples illustrate. The minimum requirement for the structure is a (GGC/A)₄sequence and neighboring nucleotides can complete the structure.

The cap-binding protein eIF4E is limiting for cap-dependent translation and its signaling control by mTORC1 and 4E-BP has been studied in great detail (Jackson et al., 2010). The results described here indicate that for a set of mRNAs the eIF4A helicase activity is required and represents the point of attack for three natural compounds, silvestrol, hippuristanol, and pateamine (Cencic et al., 2007). Moving forward, an intriguing question concerns the physiological control of eIF4A activity (Parsyan et al., 2011). In this regard, recent studies have defined the mechanics of eIF4A action (Marintchev, 2013; Marintchev et al., 2009), identified mutually exclusive potentially regulatory interactions between eIF4A and the eIF4B, eIF4G, and eIF4H factors (Rozovsky et al., 2008), and further implicated S6 kinase in the phosphorylation and signaling control of eIF4B (Kroczynska, 2009; Shahbazian et al., 2010; Shahbazian et al., 2006). The data herein indicate that these interactions define a broadly relevant layer of translational control that is distinct from the control of eIF4E by 4E-BP and mTORC1, and that is specifically aimed at a subset of transcripts.

In one embodiment, the novel sequence motifs and/or G-quadruplex structures are present in a large number of transcription factors, several known oncogenes, but also some tumor suppressor genes. A number of examples are listed and suggest that an eIF4A dependent program of translational control may have broad ramification on a cell's biology. Several genetic lesions implicated in translational activation can promote T-ALL development (e.g. PTEN, IL7R) (Palomero et al., 2007; Zenatti et al., 2011; Zhang et al., 2012).

Examples
Materials and Methods

Ribosome Footprinting. KOPTK1 cells were treated with silvestrol or DMSO for 45 minutes, followed by cycloheximide treatment for 10 minutes and then harvested for total RNA and ribosome footprint fragment isolation. Total RNA was isolated using RNA isolation kit from Qiagen (74104) and subjected to RNA sequencing. Ribosome protected fragments were isolated following published protocol (Ingolia et al., 2009). Briefly cell lysates were subjected to ribosome footprinting by nuclease treatment. Footprint fragments were purified by one step sucrose cushion and gel extraction. Deep sequencing libraries were generated from these fragments. Both total RNA and footprint fragment libraries were analyzed by sequencing on the HiSeq 2000 platform.

Sequence Alignment. Sequences were aligned to the transcripts available from the human genome sequence hg19 from UCSC public database. Ribosome footprint (RF) reads were aligned to reference genome hg19 using PALMapper (Jean et al., 2010). Only the uniquely aligned reads were used for analysis. Read length of 25- to 35-bp was selected and used to analyze the translation effect of silvestrol. Total mRNA sequencing reads were aligned to the hg19 reference using STAR (Dobin et al., 2013). The splice alignment was used, and only used the uniquely aligned reads with maximum 3 mismatches.

Footprint Profile Analysis. The genome annotation was from GENCODE project (http://www.gencodegenes.org/releases/14.html). Ribosome footprint intensity (reads per million, RPM) and the expression value (reads per kilobase per million, RPKM) were measured from total mRNA-seq data and translation values were measured from ribosome footprint data. To evaluate the translation efficiency (TE) change between silvestrol- and vehicle-treated samples, TE was calculated as RPKMfootprint/RPKMmRNA (as Thoreen et al. did recently (Thoreen et al., 2012)). Changes in ribosome footprint profiles were determined by using DEXSeq algorithm (Anders et al., 2012). DEXSeq accounts for the discrete nature of the read counts and models biological variability to avoid false positives. Ratio of TEsilvestrol/TEcontrol of all the genes was plotted and color-highlighted according to the statistical significance of DEXSeq test.

Ribosome distribution analysis. The ribosomal distribution change was evaluated between silvestrol treated samples and controls. A BED file containing all non-overlapped exonic regions was generated based on genome annotation. Then the BED file and footprint BAM files were given as an input to SAMTOOLS (Li et al., 2009a) to generate new BAM files that only included exonic alignment. The exonic BAM files were input for two conditions to rDiff (Drewe et al., 2013) to identify genes that presented significant change in ribosomal distribution.

Additional Experimental Procedures

(Non-radioactive) Metabolic labeling of nascent protein. KOPTK1 cells were labeled for nascent protein synthesis using Click-iTR AHA (L-azidohomoalanine) metabolic labeling reagent obtained from Invitrogen (cat no. C10102) as per manufacturer's instructions. Briefly, following silvestrol, Cycloheximide or DMSO treated cells were incubated in methionine free medium for 30 min prior to AHA labeling for 1 hr. Cells were fixed with 4% paraformaldehyde in PBS for 15 min, permeablized with 0.25% Triton X-100 in PBS for 15 min followed by one wash with 3% BSA. Cells were then stained using Alexa Fluor 488 Alkyne (Invitrogen cat no. A10267) with Click-iT Cell reaction Buffer Kit (Invitrogen cat no. C10269). Changes in mean fluorescence intensity as a measure of newly synthesized protein was detected by Flow cytometry analysis.

Polysome profiling. KOPTK1 cells were treated with silvestrol or DMSO for 45 minutes, followed by cycloheximide treatment for 10 minutes. Cell pellet was lysed in polysome lysis buffer (300 mM NaCl, 15 mM Tris-HCl (pH 7.5), 15 mM MgCl2, 1% TritonX-100, 0.1 mg/ml Cycloheximide, 1 mg/ml Heparin). Polysome fractions were isolated using 4 ml 10-50% sucrose density gradients (300 mM NaCl, 100 mM MgCl2, 15 mM Tris-HCl (pH 7.5), 1 mg/ml Cycloheximide, 10 mg/ml Heparin). Gradients were centrifuged in an SW40Ti rotor at 35,000 rpm for 2 hrs. Fractions of 100 ul were collected manually from the top, and optical density (OD) at 254 nM was measured.

Sequence Alignment. The human genome sequence hg19 was downloaded from UCSC public database: http://hgdownload.cse.ucsc.edu/goldenPath/hg19/chromosomes. Ribosome footprint (RF) reads were aligned to reference genome hg19 using PALMapper (Jean et al., 2010). PALMapper clips the linker sequence (5′-CTGTAGGCACCATCAAT-3′), which is technically introduced during RF library construction, and trims the remaining sequence from the 3′ end while aligning the reads to reference sequence. Briefly, the parameters for PALMapper were set as follows: maximum number of mismatches: 2; maximum number of gaps: 0; minimum aligning length: 15; maximum intron length (splice alignment): 10000; minimum length of a splicing read aligned to either side of the intron boundary: 10. Only the uniquely aligned reads were used for further analysis.

To remove ribosome RNA contamination, the footprint reads were also aligned to a ribosome sequence database using PALMapper with the same parameters except allowing splice alignment. The human ribosome sequences were retrieved from BioMart Ensembl (Flicek et al., 2013) and SILVA (Quast et al., 2013) databases and merged the results into a single FASTA file, which was used as reference sequence to align against. The rRNA-aligned reads were filtered out from hg19-aligned reads.

After removing the rRNA contamination, a portion of reads were observed that were dominated by linker sequence and Illumina P7 adapter. These reads can also be trimmed during mapping and cause false alignment. Therefore, a search was undertaken for a string of 1˜8 nt from linker sequence around the trimming site (±2 bp) allowing 1 nt mismatch. The read was removed if there was no such linker sequence. Finally, reads ≦24-bp and ≧36-bp were filtered out, and the remaining reads with aligned length from 25- to 35-bp were used to analyze the translational effects of silvestrol.

Total mRNA sequencing reads were aligned to the hg19 reference using STAR (Dobin et al., 2013). The splice alignment was performed and only use the uniquely aligned reads with maximum 3 mismatches. rRNA contaminating reads were also filtered out using the same strategy described before.

Footprint Profile Analysis. For each gene, only the number of aligned reads were counted that were mapped within exonic regions. The genome annotation was downloaded from GENCODE project (http://www.gencodegenes.org/releases/14.html). Ribosome footprint intensity (reads per million, RPM) was calculated as RPM=Ci/(N/106), where Ci is the read count for gene i, and N is the library size of silvestrol- or vehicle-treated samples. In order to eliminate the effluence of rRNA contamination, the library size was calculated after read filtering described previously. Similarly, the expression value measured from total mRNA-seq data and translation value measured from ribosome footprint data (both were referred as reads per kilobase per million, RPKM) were calculated as RPKM=Ci/(Ki·N/106), where Ki is the non-overlapped exonic region of each gene. To evaluate the translation efficiency (TE) change between silvestrol- and vehicle-treated samples, TE=RPKMfootprint/RPKMmRNA was calculated as Thoreen et al did recently (Thoreen et al., 2012).

To detect the genes that ribosome footprint profiles were significantly changed between silvestrol treated sample and control, DEXSeq (Anders et al., 2012) was used to perform the statistical test. DEXSeq accounts for the discrete nature of the read counts and it also models the biological variability which has been demonstrated in other applications to be crucial to avoid a great number of false positives. Here, DEXSeq was used in a specific way: the footprint and mRNA-seq read counts were fit into DEXseq framework, in which silvestrol treatment and control are two biological conditions, and then tested whether footprint (consisting 2 replicates for each condition) and mRNA-seq (The 3 replicates were split and recombined into two combinations such that each of them consists of two replicates) read counts were significantly different in the two conditions. The log-ratio of normalized read counts of silvestrol treated sample to control indicated whether ribosome footprint profile was increased or decreased. In the end, the ratio of TEsilvestrol/TEcontrol of all the genes was plotted, and color-highlighted them according to the statistical significance of the DEXSeq test.

In addition to studying the translation efficiency, the ribosomal distribution change was also evaluated between silvestrol treated sample and control. First, a BED file contained all non-overlapped exonic regions was generated based on genome annotation. Then the BED file and footprint BAM files were given as an input to SAMTOOLS (Li et al., 2009) to generate new BAM files only included exonic alignment. The exonic BAM files of two conditions to rDiff (Drewe et al., 2013) were input to identify genes that presented significant change in ribosomal distribution. In detail, a nonparametric test was performed implemented in rDiff to detect differential read densities. rDiff takes relevant read information, such as the mapping location and the read structure, to measure the significance of changes in the read density within a given gene between two conditions. The minimal read length was set to 25-bp, and number of permutation was set to 10000.

To plot the ribosomal distribution curves for multiple genes, read coverage of each transcript was normalized by the mean coverage value of that particular transcript. Then the UTR and coding exon length were normalized in proportion to the overall average length of corresponding regions of a group of genes. Finally all the normalized transcripts were averaged together in a vectorized way to plot the coverage distribution. The ribosomal distribution curves for a single gene were plotted in a similar way but without normalizing the read coverage, and the coverage was smoothed using ‘moving average’ smoothing algorithm.

Motif analysis. The transcripts of each gene were quantified based on the total mRNA-seq data using MISO (Katz et al., 2010). The 5′UTR of most abundant transcript was collected for predicting motifs. Both the significant genes with increased or decreased TE and altered ribosomal distribution and the corresponding background gene sets were predicted by DREME (Bailey, 2011). Over- and under-represented motifs were determined with three different settings: searching for motifs of length greater than or equal to six, nine and twelve base pairs. The predicted consensus sequences with P<1×10-4 were considered as significant motifs. The secondary structure of different gene sets was predicted using RNAfold (Hofacker, 2003) based on the same 5′UTR prepared before.

5′UTR sequences for respective group of targets were subjected to motif prediction using online available program RegRNA (A Regulatory RNA motifs and Elements Finder) (http://regrna.mbc.nctu.edu.tw/html/prediction.html) and looked specifically for motifs that occur in 5′UTR. Statistical significance for the results obtained was calculated using Fisher's exact test for count data.

T-ALL samples. Thirty-six bone marrow biopsies were collected from patients with T-ALL at multiple organizations (Universitair Ziekenhuis (UZ) Ghent, Ghent, Belgium; UZ Leuven, Leuven, Belgium; Hôpital Purpan, Toulouse, France; Centre Hospitalier Universitaire (CHU) de Nancy-Brabois, Vandoeuvre-Les-Nancy, France). The QIAamp DNA Mini kit was used to obtain genomic DNA (Qiagen 51304). The Medical Ethical Commission of Ghent University Hospital (Ghent, Belgium, B67020084745) approved this study.

Mutation analysis. NOTCH1 (exons 26, 27, 28 and 34), FBXW7 (exons 7, 8, 9, 10 and 11), PTEN (exons 1 till 9) and IL7R (exon 6) were amplified and sequenced using primers as reported in (Mavrakis et al., 2011; Shochat et al., 2011; Zuurbier et al., 2012). FBXW7, PTEN and IL7R amplification were performed using 20 ng of genomic DNA, 1×KapaTaq reaction buffer (KapaBiosystems), 1U KapaTaq DNA polymerase, 0.2 mM dNTP, 2.5 μM MgCl2, 0.2 mM forward and reverse primer in a 25 μl PCR reaction. For NOTCH1 amplification, the PCRx enhancer system (Invitrogen) was used for the PCR reaction. Reactions contained 20 ng of DNA, 2.5 U KapaTaq DNA Polymerase, 1×PCRx Amplification Buffer, 2×PCRx Enhancer Solution, 0.2 mM dNTP, 1.5 mM MgSO4 and 0.2 mM of each primer. The PCR steps were: 95° C. for 10 minutes, (96° C. for 15 sec, 57° C. for 1 minute, then 72° C. for 1 min) for 40 cycles, then 72° C. for 10 minutes. Purified PCR products were analyzed using the Applied Biosystems 3730XL DNA Analyze.

Array Complete Genomic Hybridization. PTEN deletions and MYC amplifications were detected by array CGH analysis using SurePrint G3 Human 4×180K CGH Microarrays (Agilent Technologies). First, random prime labeling of the T-ALL DNA sample and a control human reference DNA was performed with Cy3 and Cy5 dyes (Perkin Elmer), respectively. The subsequent hybridization protocol was performed according to the manufacturer's instructions (Agilent Technologies). The data was analyzed using arrayCGHbase (Menten et al., 2005).

Immunohistochemistry and Tissue Microarrays. T-cell acute lymphoblastic leukemia tissue microarrays were made as previously published (Schatz et al., 2011) using an automated tissue arrayer (Beecher Instruments, ATA-27). T-ALL samples were ascertained at Memorial Sloan-Kettering Cancer Center and were approved with an Institutional Review Board Waiver and approval of the Human Biospecimen Utilization Committee. All cancer biopsies were evaluated at MSKCC, and the histological diagnoses were based on haematoxylin and eosin (H&E) staining. TMAs were stained with the c-MYC polyclonal antibody (Epitomics 51242) using Discovery XT (Ventana) for 1 hour and a secondary anti-rabbit antibody (Vector Laboratories) for 1 hour. Histological images were captured using a Zeiss Axiocam MRc through a Zeiss Achropla lens on an Axioskop 40 microscope. Images were processed for brightness and contrast using Axiovision Rel. 4.6. Cores were scored as 0, 1, or 2 reflecting the fraction of positive cells.

Generation of mice. The ICN-driven mouse T-ALL model has been reported (Pear et al., 1996; Wendel et al., 2004). Data were analyzed in Kaplan-Meier format using the log-rank (Mantel-Cox) test for statistical significance. The surface marker analysis was as described (Wendel et al., 2004). ShRNAs against Pten and Fbxw7 have been reported in (Mavrakis et al., 2011).

Tumor transplantation. Leukemic bone marrow from mice expressing the ICN and IK6 was infected with OMOMYC and selected using puromycin. 2,000,000 cells were injected into syngeneic recipients via tail vein. Mice were monitored by blood analysis. Upon leukemia detection, tamoxifen (50 mg/kg) or vehicle treatment was performed on alternating days until mice were moribund. Severe leukemia reflects >100,000 blasts/μl and led to rapid demise of animals if untreated, whereas complete remission was defined as the absence of GFP positive leukemic blasts in the blood and bone marrow.

Real-Time Quantitative PCR. Total RNA was extracted using AllPrep DNA/RNA/Protein Mini Kit (Qiagen 80004). Normal CD3+ T-cell RNA mixed from healthy donors was purchased from Miltenyi Biotec (130-093-164). cDNA was made using SuperScript III First-Strand (Invitrogen 18080-400). Analysis was performed by ΔΔCt. Applied Biosystems Taqman GeneExpression Assays: human Myc Hs00153408_m1, hsa-miR-19b RT and TM 396, Rnu6b RT and TM 001093, and mouse Myc Mm00487804_m1.

T-ALL cell lines. T-ALL cell lines were cultured in RPMI-1640 (Invitrogen, CA), 20% fetal calf serum, 1% penicillin/streptomycin, and 1% L-glutamine. The MOHITO line was supplemented with 5 ng/mL IL2 (Fitzgerald 30R-A1022 and 10 ng/mL of IL7 (Fitzgerald 30R-AI084X).

Immunoblots. Lysates were made using Laemli lysis buffer. 30 ug of protein was loaded onto SDS-PAGE gels then transferred onto Immobilon-FL Transfer Membranes (Millipore IPFL00010). The antibodies used were α-Tubulin (Sigma T5168), β-actin (Sigma A5316), Myc (Santa Cruz Biotechnology sc-40), p-Akt 308 (Cell Signaling 9275), Akt (Cell Signaling 9272), S6 (Cell Signaling 2317), and p-S6 (Cell Signaling 2215), Notch1 (Cell signaling 3608), Myb (Santa Cruz Biotechnology, sc-517), CDK6 (Cell Signaling 3136), EZH2 (Cell Signaling 5246), Mdm2 (Santa Cruz Biotechnology, sc-965), Bcl2 (Santa Cruz Biotechnology, sc-509), Run×1 (Cell Signaling 4336), and GAPDH (Cell Signaling 5174).

Luciferase assays. Four tandem repeats of the (CGG)4 12-mer motif (GQs) or random sequence matched for length and GC content (random) were cloned into the 5′UTR of Renilla luciferase plasmid pGL4.73. Empty firefly luciferase plasmid pGL4.13 or HCV-IRES firefly were used as internal controls. Luciferase assays were performed using Dual-Luciferase Reporter Assay System (Promega E1960) following the manufacturer's instructions. GQs sequence:

(SEQ ID NO: 63)

CTAGGTTGAAAGTACTTTGACGGCGGCGGCGGTCAATCTTACGGCGGCGG

CGGACATAGATACGGCGGCGGCGGTAGAAACTACGGCGGCGGCGGATTA

GAATAGTAAA

Random Sequence:

(SEQ ID NO: 64)

CTAGGGCGCACGTACTTCGACAACGTCAGCGTTCAGCGTTCCAACGTCAG

CGTACAGCGATCCAACGTCAGCGTTCTGCGCTACAACGTCAGCGTATCCG

CGTAGCACA

Statistical analysis. All Kaplan-Meier curves were analyzed using the Mantel-Cox test. The significance of xenografted tumor size differences was determined using two-way repeated measures ANOVA tests. RT-PCRs were analyzed with two tailed t-tests.

Xenografts. 5,000,000 KOPT-K1 cells in 30% matrigel (BD 354234) were injected subcutaneously into C.B-17 scid mice. When tumors were readily visible, the mice were injected on 7 consecutive days with either 0.5 mg/kg silvestrol, 0.2 mg/kg (±)-CR-31-B, or every other day with 1 mg tamoxifen. Tumor size was measured daily by caliper. P-values were calculated using 2-way repeated measures ANOVA.

Silvestrol and (±)-CR-31-B. Each was suspended in DMSO for in vitro experiments and 5.2% Tween 80 5.2% PEG 400 for in vivo experiments. Cycloheximide (C7698) and Rapamycin (R8781) were purchased from Sigma.

Toxicity studies. Eight week-old C57Bl/6NTac female mice were randomly assigned to either control or treatment groups. Each treatment group received one daily dose of test article through i.p. injection over 5 consecutive days. Toxicity was monitored by weight loss and daily clinical observation for the 14 days following test article administration. 24 hours after the last test article administration 4 mice in each group were sacrificed and clinical chemistry, hematology and tissue specific histopathology were done at autopsy. The remaining mice (n=2 per group) were kept under observation for an additional 13 days; at that point all mice were sacrificed and clinical chemistry, hematology and tissue specific histopathology were done at time of autopsy.

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Example 1
Cap-Dependent Translation in Oncogenesis

NOTCH-driven T-ALL exemplifies the frequent activation of AKT/mTORC1 and cap-dependent translation seen in cancer. For example, in a small series of pediatric T-ALLs the common NOTCH1 HD and PEST domain mutations were confirmed (56%; 20/36 samples) (O'Neil et al., 2007; Weng et al., 2006), PTEN mutations (14%; 5/36), and PTEN deletions (11%; 4/36), resulting in mono- (16%) or bi-allelic (6%) PTEN loss (Gutierrez et al., 2009; Palomero et al., 2007; Zhang et al., 2012), and occasional IL7R mutation (3%) (Zenatti et al., 2011) (FIG. 8 A-C, Table 1).

These mutations contribute to T-cell leukemogenesis. Briefly, murine hematopoietic precursor cells (HPCs) expressing Notchl intracellular fragment (ICN) alone or in combination with additional alleles were transplanted and disease latency measured in recipient animals (FIG. 1A) (Mavrakis et al., 2011; Pear et al., 1996). Notch-ICN caused T-ALL in three months (n=14, mean latency 91.5 days), while co-expression of a short-hairpin RNA (shRNA) against Pten cut average latency in half (n=10, p<0.0001; mean latency 47.1 days) (FIG. 1B, FIG. 8D). Similarly, expression of the mutant IL7r allele (IL7R/p.L242-L243insNPC (Zenatti et al., 2011), n=4, p<0.0001, mean latency 35.5 days), or the Akt oncogene (n=4, p<0.0001, mean latency 33.5 days) dramatically accelerated leukemia onset. Notably, expression of the cap-binding protein eIF4E was sufficient to reduce latency to one month (n=4, p<0.0001, mean latency 30.75 days). Pathologically all leukemias were composed of CD4/CD8 double positive cells, and immunohistochemistry showed abundant Ki67 expression and increased S6 phosphorylation in the PTEN deficient, IL7R and AKT expressing T-ALLs (FIG. 8 E/F). Hence, the cap-binding protein eIF4E is sufficient to promote NOTCH-induced T-ALL.

A genetic approach was then used to test the requirement for eIF4E in maintaining the leukemic cells. Briefly, the 4E-binding protein (4E-BP) sequesters eIF4E and blocks cap-dependent translation (Rousseau et al., 1996). 4E-BP is negatively regulated by sequential phosphorylation at several serine residues by mTORC1, and mutation of these sites results in a constitutively active 4E-BP1 (4E-BP1(4A)) allele (Rong et al., 2008). In mixed populations of murine T-ALL cells where a fraction of cells express either 4E-BP1(4A) and GFP or an empty vector and compete with un-transduced parental cells, rapid elimination was seen of 4E-BP1(4A)/GFP expressing cells from the culture (FIG. 1D/E). Hence, eIF4E activity is required to maintain T-ALL, which indicates that targeting translation might be a therapeutic strategy.

FIG. 1 depicts the translational activation in T-ALL pathogenesis and maintenance. A) Diagram of the NOTCH-ICN-driven murine T-ALL model. B) Kaplan-Meier analysis showing time to leukemia development after transplantation of HPC transduced with NOTCH1-ICN and empty vector (black, n=9), eIF4E (green, n=4), IL7r p.L242-L243insNPC (P1) (blue, n=4), shPten (orange, n=10), or Akt (red, n=4). C) Experimental design of competition experiments and potential outcomes. D) Results as percentage of each starting GFP positive population of murine T-ALL cells partially transduced with vector/GFP or the constitutive inhibitory 4E-binding protein (4E-BP1 (4A)).

FIG. 8 depicts the PI3K pathway and translational activation in T-ALL. A-C) Diagram of mutations in human T-ALL affecting PTEN (A), IL7R (B), and NOTCH1 (C). D) Immunoblots of lysates from ICN-driven murine leukemia with the additional indicated construct, probed as indicated. E) Representative FACS profiles measuring levels of the indicated markers in murine leukemia; F) Surface marker expression on murine leukemic cells of indicated genotype (+ and − indicate < or ≧50% positive cells). G) Representative histology detailing the pathological appearance of murine T-ALLs harboring the indicated genes and stained as indicated.

Example 2
Silvestrol Blocks Cap-Dependent Translation and is Active Against T-Cell Leukemia

Based on this genetic evidence a pharmacological inhibitor was then tested. Silvestrol is perhaps the best-characterized inhibitor of the eIF4F complex, it does not target eIF4E and instead blocks the eIF4A RNA helicase by stabilizing its mRNA bound form (Bordeleau et al., 2008; Cencic, 2009). Silvestrol, and a synthetic rocaglamide analogue (±)-CR-31-B (CR) bind the same site on eIF4A (Rodrigo et al., 2012; Sadlish et al., 2013). In a dual-luciferase reporter assay, where renilla and firefly luciferase are either capped or under control of an internal ribosomal entry site (IRES) element, both drugs were confirmed to preferentially block cap-dependent over IRES-dependent translation (Bordeleau et al., 2006) (FIG. 2A, FIG. 9A).

Silvestrol has excellent single-agent activity against T-ALL in vitro and in vivo. Silvestrol was tested against primary human T-ALL samples in vitro and observed efficient apoptosis induction with IC50 values ranging from 3 to 13 nM; and confirmed activity in established cell lines (FIG. 2B, FIG. 9B). The results were similar for similar the analogue CR (not shown). Notably, silvestrol showed equal activity against PTEN wild type and PTEN mutant cell lines and primary T-ALL cells. The least sensitive line (MOLT-16) carries a c-MYC translocation (Shima-Rich et al., 1997). Similarly, murine T-ALL cells engineered to express Akt, mutant IL7R, eIF4E, or an shRNA against Pten showed no significant difference in sensitivity indicating that silvestrol can overcome their activity (Figure S2C). In vivo both silvestrol and CR were effective against xenografted T-ALL cells (FIG. 2C, Figure S2D/E). Treatment of KOPT-K1 tumor (˜1 cm3) bearing NOD/SCID mice with systemic administration of silvestrol (0.5 mg/kg, d 0-6) and CR (0.2 mg/kg, d 0-6) produced a significant delay in tumor growth (Silvestrol: n=7, p<0.001; CR: n=8, p<0.001) (FIG. 2C, FIG. 9D/E). Pathologic analysis of treated tumors showed diffuse apoptosis by TUNEL and loss of proliferation by Ki-67 (FIG. 2D). Notably, no severe toxicity, death, or weight loss was observed. CR treatment at therapeutic doses showed a reversible drop in white cell count with a nadir on day 19, and no other changes in blood counts or bone marrow cytology, or serum chemistry (FIG. 9F-O, Table 2). No changes were observed in intestinal histology, which is a major concern with gamma secretase-inhibitors (FIG. 9J) (Real et al., 2009). Hence, single agent silvestrol or CR treatment is effective against T-ALL and is safe in vivo.

Silvestrol acts in a manner that is distinct from mTORC1 inhibitors. For example, the predominant inhibition of S6 kinase instead of 4E-BP and feedback activation of AKT (S308 phosphorylation) are thought to hinder the therapeutic effect of rapamycin (FIG. 2E) (Choo et al., 2008; Kang et al., 2013; Thoreen et al., 2009); 2)(O'Reilly et al., 2006; Sun et al., 2005; Thoreen et al., 2009; Wan et al., 2007). This feedback mechanism is active in KOPT-K1 cells, where Rapamycin-induced loss of ribosomal S6 phosphorylation and feedback activation of AKT (T308) was observed (FIG. 2F). By contrast, selective inhibition of eIF4A with silvestrol or CR does not affect S6 kinase activity and did not lead to phosphorylation of AKT (T308). Hence, selective inhibition of eIF4A is sufficient for therapeutic activity and avoids feedback activation of upstream AKT signaling.

FIG. 2 shows silvestrol blocks cap-dependent translation and has single-agent activity against T-ALL. A) Diagram of the dual reporter system expressing a capped renilla luciferase transcript (red) and firefly luciferase under control of the hepatitis C IRES-element (black); (below) Relative levels of renilla luciferase (red, cap-dependent) and firefly luciferase (black, IRES dependent) upon treatment with vehicle (DMSO), silvestrol or the synthetic analogue (±)-CR-31-B. B) Viability of T-ALL primary patient samples treated with silvestrol for 48 hours; PTEN status is indicated. C) Tumor size of KOPT-K1 xenografts upon treatment with (±)-CR-31-B (0.2 mg/kg) or vehicle (see Figure S2 for longer follow up and silvestrol treatment data). D) Immunohistochemistry of (±)-CR-31-B treated KOPT-K1 tumors stained as indicated. E) Simplified diagram of rapamycin and silvestrol mechanism of action. F) Lysates of KOPT-K1 cells treated with vehicle (Veh), Rapamycin (Rapa: 25 nM), (±)-CR-31-B (CR: 25 nM), or silvestrol (Silv: 25 nM) for 48 hours and probed as indicated.

FIG. 9 shows testing silvestrol and the synthetic analogue (±)-CR-31-B in T-ALL. A) Dual luciferase reporter assay, shown are relative levels of each firefly (cap-dependent) and renilla (IRES-dependent) luciferase upon treatment with silvestrol or (±)-CR-31-B. B) IC50 values for silvestrol and CR in a panel of human T-ALL lines. C) Silvestrol effect on murine T-ALLs with the indicated genetic lesions; curves are mean of triplicates and differences between the genotypes did not reach significance. D) KOPT-K1 xenograft studies. Shown is the tumor volume during and after systemic treatment with CR or vehicle (intraperitoneal injection, 0.2 mg/kg on days indicated by red arrows). E) Tumor volume upon intraperitoneal treatment with vehicle or silvestrol (0.5 mg/kg on days indicated by red arrows). F-0) Toxicity studies with (±)-CR-31-B. F) Animal weights during and after CR treatment (intraperitoneal injection, 0.2 mg/kg on days indicated by red arrows), red=CR, black=vehicle. G-I) Counts of white blood cells (G), red cells (H), and platelets (I) 14 days after cessation of CR treatment, blue lines indicate the species and strain specific reference range, n.s. indicates not significant. J) Representative histology of gastrointestinal tract (small intestine) on the indicated days during and after (±)-CR-31-B treatment; K-O) Serum levels of alanine aminotransferase (ALT) (K), aspartate transaminase (AST) (L), albumin (M), total bilirubin (N), and creatinine (O) two weeks after cessation of treatment with 0.2 mg/kg CR or vehicle, blue lines indicate the species and strain specific reference range, n.s. indicates not significant.

Example 3
Transcriptome-Scale Ribosome Footprinting Defines Silvestrol-Sensitive Translation

Next, use of the recently developed ribosome footprinting technology (Ingolia et al., 2009) was employed to measure precisely how silvestrol affected protein translation. Briefly, KOPT-K1 cells were treated with 25 nM of silvestrol or vehicle, cells collected after 45 minutes, then isolated and deep-sequenced total RNA and ribosome footprints (RFs) prepared (FIG. 3A). The early time point was chosen to capture effects on translation and minimize secondary transcriptional changes and cell death. First, RFs per mRNA were determined which, after correcting for transcript levels and length, indicated changes in translational efficiency (TE). Out of six measurements two outliers were removed (see methods); the remaining two biological replicates showed excellent consistency of read counts for each gene (Control: R2=0.90; Silvestrol: R2=0.88; data not shown). Raw reads were aligned to the human reference genome hg19 allowing for splicing alignment and using only uniquely aligned reads. Reads mapping to ribosomal RNAs, non-coding RNAs (Guttman et al., 2013) were then removed, and linkers used in library generation, incomplete and spurious alignments, and aligned lengths between 25 and 35 nucleotides (see methods) (FIG. 10A/B). The majority of the remaining reads now mapped to protein coding genes (FIG. 10C/D). The total number of RF reads that mapped to exons was 3.2 million in control and 3.4 million Silvestrol samples and this corresponded to ˜11,128 protein coding genes.

Silvestrol produced an immediate and broad inhibitory effect on cap-dependent translation. RF reads were fewer in number and showed a wider variation between control and silvestrol than total RNA sequences indicating minimal transcriptional variation (FIG. 10E). The number of ribosomes occupying a given transcript is given as gene specific RF reads per one million total reads (RPM). The RPM frequency distribution of control and silvestrol samples were overlapping, indicating that silvestrol equally affected mRNAs with high and low ribosome occupancy (FIG. 10F). Measurements of nascent protein synthesis with L-azidohomoalanine (AHA) labeling confirmed a broad inhibitory effect on translation (max. reduction with silvestrol ˜60%; p(Silv. vs. Veh.)=3.6×10−3, and 80% with cycloheximide, p(CHX vs. Veh.)=2×10−4) (FIG. 10G). Consistently, analyses of polyribosome bound RNA indicated loss of polyribosome bound RNA (fractions 30-40) upon silvestrol treatment (FIG. 10H).

Silvestrol affected the translational efficiency of specific sets of mRNAs. To calculate the translational efficiency (TE) for each mRNA the RF frequency was normalized to the length of the corresponding mRNA yielding an RF density (expressed as RPKM: reads per kilobase per million reads), and was corrected for total mRNA expression. Overall RPKM values for RF from vehicle and silvestrol treated samples were significantly correlated (R2=0.94) indicating a broad inhibitory effect on translation (FIG. 3B). The DERseq algorithm (Differential Expression-normalized Ribosome-occupancy) was used, based on the reported DEXseq algorithm (Anders et al., 2012), to identify mRNAs that were strongly affected by silvestrol (see method). A cut-off at p<0.03 (corresponding to a Z-score >2.5) was used to define groups of mRNAs whose translational efficiency (TE) was either most (TE down; red) or least (TE up; blue) affected by silvestrol compared to most other mRNAs (background; grey) (FIG. 3C, see also U.S. application Ser. No. 61/912,420, filed Dec. 5, 2013; and Wolfe A L, Singh K, Zhong Y, Drewe P, Rajasekhar V K, Sanghvi V R, Mavrakis K J, Jiang M, Roderick J E, Van der Meulen J, Schatz J H, Rodrigo C M, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher M A, Speleman F, Porco J A Jr, Pelletier J, Ratsch G, Wendel H. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature. 2014 Sep. 4; 513(7516):65-70. doi: 10.1038/nature13485. Epub 2014 Jul. 27, both of which are incorporated herein by reference in their entireties) (Thoreen et al., 2012). The TE down group included 281 mRNAs (220 have annotated 5′UTRs), TE up included 190 mRNAs, and the background list included 2243 mRNAs. These groups were used to define the characteristics of differentially affected mRNAs.

FIG. 3 depicts transcriptome-scale ribosome footprinting defines silvestrol's effects on translation. A) Schematic of the ribosome footprinting experiments (see text for details). B) Ribosome density for transcripts across control and silvestrol samples (ribosomal footprint (RF) reads per kilobase per million reads (RPKM)). The correlation (R2=0.94) indicates a broad effect on translation and transcripts with significantly differential changes in ribosome density are indicated as red and blue dots. C) Frequency distribution of the ratio of translational efficiency (TE=foot print density corrected for total mRNA abundance) in control and silvestrol treated samples (TESilvestrol/TEcontrol). Red and blue areas indicate groups of more (TE down) or less (TE up) affected mRNAs with a cut-off at p<0.03; a second cut-off is indicated light blue/red for p<0.13). D) Comparison of 5′UTRs lengths for TE down versus background genes. Mathematical density is scaled such that all values on the x-axis sum to 1; red: TE down, black: background genes, *: mean value. E) Prevalence of the indicated 5′UTR motifs among the TE down and background genes. F) A consensus 12-mer motif enriched in the TE down genes. G) Illustration of base-pair interactions in a predicted G-quadruplex based on the sequence motif. H) Enrichment of predicted 5′UTR G-quadruplex structures in the TE down gene set (* indicates p<0.05). I) Venn diagram indicating the overlap of genes containing 12-mer motifs and G-quadruplexes in TE down genes. J) Schematic of the NDFIP1 5′UTR showing a G-quadruplex region matching the 12-mer (GGC)4 motif.

FIG. 10 depicts ribosome profiling quality control data and effects on translation. A and B) Read counts by length of mapped sequence before and after filtering rRNA, linker reads, non-coding RNAs, short mapped sequences (“noisy” reads; see text and method for details). C and D) Read length frequency histograms and mapping analysis of ribosome footprint data after quality control filtering for vehicle treated cells (C) or silvestrol treated cells (D). E) Silvestrol induced changes in total RNA (log 2 Fold change RPKM) and ribosome protected RNA (RF). F) Histogram of all genes' ribosome footprint intensity (measured as unique read number per million per gene, RPM) for silvestrol and vehicle treated cells indicating silvestrol affected mRNAs were broadly distributed (see text for details). G) Mean fluorescence intensity of incorporated L-azidohomoalanine (AHA) in newly synthesized proteins in KOPTK1 cells treated with vehicle (DMSO), silvestrol (Silv. 25 nM), or Cycloheximide (CHX 100 nM) for the indicated time period. H) Polyribosome profiles of silvestrol (25 nM) or vehicle (DMSO) treated KOPT-K1 cells showing OD254 absorption across the ribosome containing fractions. I) Length comparison of 5′UTRs of TE up genes and a background gene set; *: mean J) Percentage of TE up genes and background genes containing the indicated sequence motifs; *: p<0.001. K) Consensus logos showing the three most significant 9-mer motifs enriched in TE down genes. The TE up genes do not have a motif. L) Venn diagram indicating the overlap between genes containing 9-mers and G-quadruplexes in TE down genes.

Example 4
Hallmarks of eIF4A-Dependent and Silvestrol-Sensitive Transcripts

5′UTR length has been implicated in translational control (Hay and Sonenberg, 2004), although a recent study found no effects of UTR length on mTORC1-dependent translation (Thoreen et al., 2012). Comparing the 5′UTR length across TE up, TE down, and background groups (as described in U.S. application Ser. No. 61/912,420, filed Dec. 5, 2013; and Wolfe et al., Nature. 2014 Sep. 4; 513(7516):65-70), it was observed that mRNAs with longer 5′UTRs were significantly enriched among the most silvestrol-sensitive mRNAs (TE down: mean UTR length 368 nucleotides; background: mean 250 nucleotides; p(Silvestrol vs. Control)=7.6×10−12 using two-sample Kolmogorov-Smirnov) (FIG. 3D). On the other hand, the TE up group showed no significant difference in 5′UTR length (TE up: 265 nucleotides; p(Silvestrol vs. Control)=0.165) (FIG. 10I).

Known translation regulatory elements were sought. For example, TOP sequences (cytidine in pos. 2 followed by 4-14 pyrimidines) (Meyuhas, 2000), TOP-like sequences (cytidine in pos. 1-4 and >5 pyrimidines) (Thoreen et al., 2012), internal ribosome entry sites (IRES) (Pelletier and Sonenberg, 1988), and pyrimidine rich translational elements (PRTEs) (Meyuhas, 2000). Comparing TE down and the background lists no predilection was found for TOP, TOP-like, PRTE, or IRES elements (FIG. 3E). On the other hand, the TE up group showed a significant enrichment for IRES elements and this is consistent with the dual-luciferase reporter assay and previous characterization of IRES dependent translation (Bordeleau et al., 2006) (FIG. 10J; see also FIG. 2A, FIG. 9A).

Next it was sought to identify a sequence motif that might confer eIF4A dependence. The DREME algorithm was used to look for significantly enriched sequences in the TE down and TE up groups compared to the background list (as described in U.S. application Ser. No. 61/912,420, filed Dec. 5, 2013; and Wolfe et al., Nature. 2014 Sep. 4; 513(7516):65-70) (Bailey, 2011). No motif was found in the TE up group of mRNAs. However, the analysis revealed a 12-mer (GGC)₄motif that was significantly over represented among the TE down transcripts and present in 94 out of 220 genes (p<2.2×10-16) (FIG. 3F, Table 3A). In addition, 14 shorter 9-mer motifs were found that were similarly enriched in the TE down group and occurred in 177 of 220 genes (p<4.2ex10-15) (Figure S3K, Table 3B). P-values were computed using a one-sided binomial test while accounting for the different 5′ UTR lengths. A significantly higher than expected number of motif occurrences than explained by the larger UTR lengths were found (p<2.2×10-16).

Whether silvestrol-sensitive mRNAs might have specific structural features that set them apart from less affected transcripts was considered. Using the program RNAfold (http://rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi) the background, TE up, and TE down genes were modeled and a striking enrichment was observed for G-quadruplex structures among the TE down genes (p=2×10-11) (FIG. 3G-I). Specifically, 79 of the 220 TE down transcripts with annotated 5′UTRs harbored at least one G-quadruplex. Moreover, in 48 out of 79 transcripts, G-quadruplex structures perfectly co-localized with the (GGC)4 12-mer sequence motif (FIG. 31, Table 3C). Briefly, G-quadruplex structures are based on non-Watson-Crick interactions between at least four paired guanine nucleotides that align in different planes and are connected by at least one linker nucleotide (FIG. 3F/G) (Bugaut and Balasubramanian, 2012). Most often two guanines were observed separated by an intervening cytosine and sometimes an adenine (FIG. 3F). The NDFIP1 5′UTR exemplifies the folding and typical pattern observed, with more than one G-quadruplex and one that directly matches the 12-mer (GGC)4 motif and a second larger structure that is formed by a longer nucleotide sequence including elements that are similar although not identical to the canonical (GGC)4 motif (FIG. 3J). While a 9-mer sequence is insufficient to form the structure, these motifs are found to be highly enriched within G-quadruplex structures. For example, the most common 9-mer motif overlapped with G-quadruplex structures in 45% (p=2.2×10-6), the second most common in 21% (p=1.4×10-10). In these instances, nucleotides adjacent to the motif completed the structure (Table 4, illustrated in FIG. 11H). Together, these analyses indicate that long 5′UTRs and a (GGC)4 motif or highly similar sequence patterns that can form G-quadruplex structures are the hallmarks of eIF4A-dependent and silvestrol-sensitive translation.

FIG. 11 shows the analysis of genes with differential ribosomal distribution (rDiff positive set). A) Representation of ribosome coverage for all 847 transcripts with significant changes in distribution between silvestrol (red) and vehicle (black); corresponding to the rDiff positive gene list. Both RF coverage and transcript length are normalized for comparison; translation start and stop sites are indicated by blue lines. B-C) Ribosomal distribution plots as in A showing how silvestrol affects ribosome distribution in all TE up genes (B) and all TE down genes (C). D) Length comparison of 5′UTRs of genes with significantly altered ribosomal distribution (rDiff positive: red) and background genes (black); *: mean value. E) Percentage of rDiff positive genes and background genes containing the indicated sequence motifs.* indicates p<0.05. F-G) Venn diagrams indicating overlap between genes containing 12-mers (F) or 9-mers (G) and G-quadruplexes in rDiff positive genes. H) Schematic of the ADAM10 5′UTR with G-quadruplexes and indicating an example of a 9-mer sequence contributing to the G-quadruplex. I) Diagram of Renilla luciferase expressed from four G-quadruplexes in tandem (GQs, red) and Firefly luciferase expressed from the HCV IRES (white). J) Relative amounts of Renilla luciferase expressed from the GQ construct in 3T3 cells and normalized to IRES/Firefly with either empty vector or the indicated genes (* p<0.05). K) Relative amounts of Renilla luciferase expressed from the GQ construct in 3T3 cells and normalized to IRES/Firefly with either empty vector or the indicated genes, treated with silvestrol (25 nM) for 24 hours.

Example 5
Silvestrol Causes an Accumulation of RFs in the 5′UTR of Sensitive Transcripts

Next, the distribution of ribosomes was examined along the transcript as this might provide an additional indication of eIF4A sensitive translation (FIG. 4A). Note that the footprinting methodology provides exact sequence and positional information for each RF, and using the rDiff algorithm significant changes in read density were identified across the length of any given transcript (see method) (Drewe et al., 2013). A p-value cutoff of p<0.001 was used to identify a group (the rDiff positive set) of 847 protein-coding transcripts (641 with an annotated 5′UTR) that showed the most significant change in RF distribution (Table 5). These transcripts showed an accumulation in the 5′UTR and corresponding loss of coverage across the coding sequence. This silvestrol effect is most pronounced for the 62 genes that show decreased TE (TE down) and significant change in rDiff whereas it is absent in the TE up group (FIG. 4B, FIG. 11A-C, Table 6).

Similar to the TE down group an enrichment of longer 5′UTR in the rDiff positive set was found (rDiff pos.: n=641; mean length 271 nucleotides; Background (rDiff negative=no significant change): n=976, mean UTR length: 230 nucleotides; p=0.004) (Figure S4D). No significant enrichment for TOP, PRTE, or IRES elements was detected, however there was a small and significant drop in TOP-like sequences (Figure S4E). The DREME analysis for sequence motifs identified a significant enrichment for a 12-mer and three 9-mer motifs among rDiff positive genes (p=2.2×10-16) (FIG. 4C/D, Table 4, Table 7A/B). Among 641 genes in the rDiff group, the 12-mer motif occurred in 232, and an additional three 9-mer motifs were found in 322 genes. Notably, the motifs were nearly identical to the TE down motif (FIG. 3). Again, the 12-mer and 9-mer motifs co-localized to the majority of predicted G-quadruplexes observed in the rDiff positive gene set and this is illustrated with the ADAM10 5′UTR (FIG. 11F-H, Table 4, Table 7C). Hence, two different analyses—translation efficiency and RF distribution—point to the exact same patterns in eIF4A-sensitive transcripts: longer 5′UTRs with variations on the theme of a (GGC)4 sequence capable of G-quadruplex formation.

Next, directly testing the translational effect of the 12-mer sequence motif was sought. Briefly, a luciferase reporter system was constructed to directly compare four 12-mer motifs in tandem reflecting the common occurrence of multiple motifs in sensitive mRNAs (GQ construct) to a random sequence of equal length and GC content (control construct) and using an IRES-driven firefly luciferase as an internal control (FIG. 4E). First, treatment with silvestrol (25 nM) reduced the translation of the GQ construct and did not reduce the translation of the control luciferase. The RNA helicases DHX9 and DHX36 have been implicated in resolving G-quadruplex structures (Booy et al., 2012; Chakraborty and Grosse, 2011), however predominant expression was found of eIF4A in T-ALL (FIG. 4G) (Van Vlierberghe et al., 2011). Further direct testing was done of the effect of RNAi-mediated eIF4A knockdown in the same assay and a striking decrease in the translation from the GQ reporter observed, with little effect on the control sequence (FIG. 4H/I). Whether upstream activators or translation factors could enhance translation of the GQ construct was explored. It was found that only eIF4G could increase translation and that neither Akt, eIF4E, or eIF4A expression were sufficient (FIG. 11I/J). This is consistent with the notion that eIF4A levels are not limiting under physiological conditions and that additional factors (e.g. eIF4G) are needed for full eIF4A activation (Feoktistova et al., 2013; Oberer et al., 2005; Ozes et al., 2011). However, upon silvestrol treatment, it was observed that increased expression of wild type eIF4A or an RNA-binding site mutant protein (P159Q—homologous to S. cervesiae P147Q (Sadlish et al., 2013)) could render translation of the GQ reporter construct insensitive to silvestrol (FIG. 11K). Hence, pharmacologic and genetic evidence indicates that the 12-mer motif enriched in silvestrol sensitive transcripts requires eIF4A for translation.

FIG. 4 shows that silvestrol affects ribosome distribution in a subset of mRNAs. A) Diagram of differential ribosomal distribution along the length of a transcript. B) Representation of ribosome coverage for 62 TE down transcripts with changes in ribosomal distribution (rDiff positive); silvestrol (red), vehicle (black). RF coverage and transcript length are normalized for comparison, translation start and stop sites are indicated. C) rDiff positive genes were enriched for 9-mer and 12-mer motifs compared to background genes (* indicates p<0.05). D) The rDiff positive genes are enriched for the indicated 12-mer GC-rich consensus motif. E) Schematic of constructs expressing the indicated luciferase with 5′UTRs containing four 12-mer motifs in tandem (GQs, red), a random sequence matched for length and GC content (control, black), and the HCV IRES (white). F) Relative amounts of Renilla luciferase (normalized to Firefly) expressed from the GQs (red bars) or control construct (black bars), treated as indicated for 24 hours (* indicates p<0.05). G) Analysis of mRNA expression from (Van Vlierberghe et al., 2011) of the indicated RNA helicases in normal T-cells and T-ALL cells (* indicates p<0.05). H) Immunoblots of lysates from 3T3 cells with empty vector or sh-eIF4A and probed as indicated. I) Relative amounts of Renilla luciferase (normalized to Firefly) expressed from the GQs (red bars) or control construct (black bars), with empty vector or sh-eIF4A (* indicates p<0.05).

Example 6
Transcripts Affected by Silvestrol

The most silvestrol sensitive transcripts in the TE down group and the rDiff positive set include many genes with known roles in T-ALL (FIG. 5A/B). Categorization by gene ontology reveals a preponderance of transcription factors, many oncogenes, but also potential tumor suppressors (Figure S5A/5B). Sub-grouping of TE down genes by 5′UTR features (12-mer, 9-mer motif, and G-quadruplex structures) illustrates how sometimes multiple features occur in the same transcripts (Figure S5C-E). Exploring individual RF distribution graphs (normalized for mean RF count and gene length) illustrates recurrent patterns and also variations. For example, the c-MYC transcript (TE: p=1.3×10-4; rDiff: p=3×10-8) harbors six 9-mer motifs in its 5′UTR which correspond to peaks in RF density (FIG. 5C). Similarly, MDM2 (TE: p=0.94; rDIff: p=4.9×10-7) and RUNX1 (TE: p=4×10-3; rDIff: p=5.2×10-3) harbor multiple motifs and show a 5′UTR RF accumulation and drop across the coding region (FIG. 5D/E). CDK6 (TE: p=4×10-8; rDIff: p=4.7×10-5) shows the same pattern, and while the DREME analysis did not retrieve the typical motif it might harbor an alternate element (FIG. 5F). BCL2 (TE: p=8.6×10-3; rDIff: p=6.0×10-1), and BCL11B (TE: p=5.4×10-10; rDIff: p=1.0×10-8) have multiple 9-mer and 12-mer motifs and these transcripts show a drop in 5′UTR RF counts and peak shifts in their exonic regions (FIG. 5G/H). Several housekeeping genes have no recognizable motif and in particular actin shows no detectable effect of silvestrol on RF patterns (FIG. 5I-K).

FIG. 5 shows that many cancer genes are differentially affected by silvestrol. A) TE down genes in silvestrol treated KOPT-K1 ranked by translational efficiency (red, up to p=0.01). B) rDiff positive genes ranked by changes in ribosome distribution (up to p=0.001). C-K) Distribution of ribosomal footprints for the indicated genes. Silvestrol: Red; Vehicle: black; purple dots: 9-mer motifs; blue dots 12-mer motif.

FIG. 12 shows that gene ontology analysis of silvestrol sensitive genes. A) Number of genes in TE down group with G-quadruplex, 12-mer and 9-mer motif in the indicated gene family classifications. B) Number of genes in rDiff positive group with G-quadruplex, 12-mer and 9-mer motif in the indicated gene family classifications. C-E) Representative transcription factors and oncogenes with G-quadruplex (C), 12-mer (D), and 9-mer (E) motif in TE down genes, ranked by significant changes in translational efficiency.

Given the complexity of the RF data analysis, it was important to directly confirm loss of expression for at least some of these proteins. Briefly, immunoblots on JURKAT and KOPT-K1 cells treated with silvestrol (25 nM) and loaded with equal amounts of total protein confirmed dramatic loss of MYC, NOTCH1, BCL2, and CCND3 proteins (FIG. 6A). The effect on MYC was especially striking, it was dose dependent (FIG. 6B), lasted for 48 h, and was also achieved in xenografts in vivo (Figure S6A-B). Others whose expression was somewhat less decreased included MYB, CDK6, EZH2, and RUNX1/AML1. As expected, ACTIN, TUBULIN, and GAPDH were not affected (FIG. 6A). The same result was confirmed with the silvestrol analogue (CR) (Figure S6C). The effects were indeed posttranscriptional and no decrease was observed in the corresponding mRNA expression (FIG. 6C). The small and significant increase in MYC mRNA levels might be consistent with prior reports of a MYC auto-regulatory mechanism (Penn et al., 1990a; Penn et al., 1990b) (FIG. 6C).

Genomic studies have implicated many silvestrol-sensitive genes in T-ALL and other cancers. For example oncogenic mutations of NOTCH (Weng et al., 2004), increased CDK6/CCND3 (Sawai et al., 2012), and amplifications of MYB (Lahortiga et al., 2007) have been reported in T-ALL. Similarly, a brief survey of mRNA expression using RNAseq on 9 primary T-ALL samples compared to 4 T-cell samples confirms increased expression of NOTCH, MYB, CDK6, and BCL2 in T-ALL (FIG. 6D). Increased MYC activity has also been implicated in T-ALL (Gutierrez et al., 2011a; Palomero et al., 2006), and it was observed abundant MYC protein expression in ˜70% of T-ALLs by immunohistochemistry (Figure S6D). A direct tested was conducted on some of these genes for their role in T-ALL using the same mouse model described above (FIG. 1A). Briefly, Myb (n=4, p<0.0001), a mutant Ccnd3 (T283A) (n=5; p<0.0001), Bcl2 (n=4, p<0.0001), and p53 loss (as a surrogate for Mdm2; n=3; p<0.0001) accelerated leukemogenesis in the Notch context in vivo (FIG. 6E). However, silvestrol also affected candidate tumor suppressors in T-ALL, for example BCL11b (Gutierrez et al., 2011b), RUNX1 (Della Gatta et al., 2012; Giambra et al., 2012), and EZH2 (Ntziachristos et al., 2012). Direct testing of the effect of EZH2 knockdown (n=6, p<0.0001) demonstrated that EZH2 indeed acts as a tumor suppressor in T-ALL in vivo (FIG. 6E).

Given the pleiotropic effects of eIF4A inhibition it was considered which of its target genes may account for the drug's anti-leukemia effect. The MYC oncogene is a first candidate, because of silvestrol's powerful effects on MYC levels and its known oncogenic role in this cancer (Gutierrez et al., 2011a; Palomero et al., 2006). Moreover, genetic MYC blockade using the tamoxifen-inducible OmomycER allele (Soucek et al., 2008) readily induces cell death and clears T-ALL cells from the marrow leading to an extended survival in leukemic animals (nOMO=9, ncontrol=10; p=0.002) (FIG. 6F and inset). However, IRES-driven expression of MYC alone was unable to protect murine T-ALL cells from silvestrol. Similarly, IRES-driven expression of additional oncogenes including BCL2, NOTCH1, CCND3 (T283A) was not protective. Instead, cells expressing both IRES-MYC and IRES-BCL2 were significantly selected upon silvestrol treatment (FIG. 6G). These results suggest that silvestrol acts by disrupting the production of multiple pro-oncogenic multiple factors that are required to maintain the leukemia.

FIG. 6 depicts validation of selected silvestrol targets. A) Immunoblots of lysates from human T-ALL lines treated with silvestrol (25 nM) and probed as indicated. B) Immunoblots of lysates from JURKAT cells treated with escalating doses of silvestrol and probed as indicated. C) mRNA levels for the corresponding genes treated with vehicle (DMSO, black) or silvestrol (red, 25 nM); D) Volcano plot of mRNA expression changes of all TE Down and rDiff genes in T-ALL samples (n=9) compared to normal thymocytes (n=4). E) Kaplan-Meier analysis showing time to leukemia development (as in FIG. 1B). Wild-type HPCs transduced with NOTCH1-ICN and empty vector (black, n=14), Myb (red, n=4), Ccnd3 T283A (orange, n=5), or shEzh2 (orange, n=10), vavP-Bcl2 (brown, n=4), p53−/− (green, n=3). F) Effect of OmoMYCER activation on survival of leukemic animals; (d=0 represents start of therapy/tamoxifen (TAM) administration). Inset: clearance of GFP expressing murine T-ALL cells from the marrow upon OmomycER activation (Untr: untreated, TAM: tamoxifen). G) Competition experiment (as in FIG. 1C/D) showing the percentage of each starting GFP positive population of murine T-ALL cells partially transduced with the indicated constructs and treated with silvestrol (* indicates p<0.05).

FIG. 13 depicts the relative contribution of MYC and other silvestrol targets in T-ALL. A) Time course analysis of protein expression in KOPT-K1 cells treated with CR (25 nM) for the indicated number of hours. B) Immunoblot on CR or vehicle treated KOPT-K1 xenografts, probed as indicated. C) Immunoblots of lysates from human T-ALL lines treated with CR (25 nM, 24H) and probed as indicated. D) Representative section of tissue microarrays (TMA) representing 14 human T-ALLs and stained for MYC (lower panel) Scoring of the T-ALL MYC TMA: ‘0’=0%-25% positive cells, ‘1’=25%-75% positive cells, ‘2’=75%-100% positive cells. Normal spleen, kidney, and lymph node negative controls were present on the same slides. E) Histology from tamoxifen treated (50 mg/kg) xenografted T-ALL tumors expressing a control vector or OmomycER and stained as indicated. F-I) Immunoblots of lysates from murine T-ALL cells expressing either vector control or IRES-MYC (F), IRES-CCND3 T283A (G), IRES-ICN (H), or IRES-BCL2 (I) and probed as indicated.

Example 7
Study of G-Quadruplex Unwinding Mechanisms

A FRET-based assay was set up for measuring the effect of RNA helicases on G-quadruplex unwinding, screening proteins that can unwind G-quadruplexes and identify small molecules that stabilize the G-quadruplex structure. An RNA oligonucleotide (1XTEDownMotif 5′-UAGAA ACUAC GGCGG CGGCG GAAUC GUAGA; SEQ ID NO:65) containing the G-quadruplex motif was labeled with fluorophore FAM on the 5′ end and quencher BHQ1 on the 3′end. When folded, the labeled GQ RNA oligonucleotide will exhibit minimum baseline fluorescence. Addition of specific RNA helicase such as EIF4A with ATP and/or small molecules would result in unwinding and increase in fluorescence signal measured in real time, as shown in FIG. 14A.

FIG. 14B shows the optimization of fluorescence quenching assay using labeled RNA G-quadruplex oligonucleotide. Fluorescence was measured as function of concentration using G-quadruplex RNA with or without KCl. Without KCl fluorescence intensity increases as a function of concentration while in the presence of KCl it remains stable, suggesting the formation of a stable G-quadruplex structure in the presence of KCl.

Fluorescence measured as function of concentration using a mutant RNA (1XMutant; 5′-UAGACCCUGCAACGUCAGCGUAGUCGUAGC; SEQ ID NO:66) with or without KCl is shown in FIG. 14C. Fluorescence intensity increase as a function of concentration irrespective of KCl suggesting no particular secondary structure present in the mutant RNA oligonucleotide.

In FIG. 14D, the G-quadruplex versus mutant RNA oligonucleotide were compared using the fluorescence quenching assay. The fluorescence intensity of the G-quadruplex RNA remains stable and lower compared to the mutant RNA oligonucleotide. Mutant RNA shows an increase in fluorescence intensity as a function of concentration. Chemical unwinding using formamide results in increase of fluorescence intensity of both G-quadruplex and mutant RNA oligonucleotide.

Example 8
Sensitivity of Cancers to Silvestrol

The IC50 of silvestrol in several small cell lung cancer lines was evaluated. As shown in FIG. 15, low IC50s were observed in cell lines NCI-H211, NCI-H446, NCI-H2171, NCI-H82, NCI-H526, NCI-H196 and NCI-H889, indicating high sensitivity to silvestrol. The IC50 values are shown in the left figure and the individual viability curves are shown at the right.

A range of sensitivities from renal carcinoma lines ACHN, A498, CAKI-1, CAKI-2 to 786-O was demonstrated, as shown in FIG. 16.

In addition, IC50s of 2 to 20 nM have been obtained with neuroblastoma cell lines SKNAS, CLBGA, IMR32 and N206. Pancreatic cancer line PANC-1 show sensitivity to 20 nM silvestrol and a loss of KRAS expression.

In addition to the renal cell carcinoma and small cell lung cancer lines mentioned above, about 60 cancer cell lines were evaluated for silvestrol sensitivity as shown in FIG. 17. Cancers including T-ALL, transformed follicular lymphoma, mantel cell lymphoma, breast cancer, ovarian cancer, hepatocellular carcinoma, and non-small cell lung cancer, as well as gastric cancer, pancreatic carcinoma, Ewing sarcoma and lung adenocarcinoma. FIG. 18, lower left panel, shows that MYC expression is not correlated with silvestrol sensitivity, indicating that MYC expression alone is not predictive of potential sensitivity of a tumor to silvestrol or other eIF4A inhibitor compounds as described herein, and indicates that the predictors of silvestrol sensitivity as described herein with the exclusion of MYC expression are useful for determining whether a patient's cancer will be sensitive to silvestrol.

Example 9
The Reporter Assay Determines Activity of Hippuristanol and Pateamine A

Using the dual-luciferase reporter assay described above, where renilla and firefly luciferase are either capped or under control of an internal ribosomal entry site (IRES) element, both hippuristanol and pateamine A were shown to preferentially block cap-dependent over IRES-dependent translation (FIG. 19).

Example 10
In Vitro Data on Silvestrol in Small Cell Lung Cancer

The in vitro activity of silvestrol was evaluated against a panel of small cell lung cancer cell lines, shown in FIG. 20A. In these cell lines, the effect of silvestrol on key target proteins MYC, EZH2 and cKit were determined (FIG. 20B, C). FIG. 21A shows the effect of silvestrol on H82 small cell lung cancer cells in the presence and absence of serum. FIG. 21B shows the effect of silvestrol alone and in combination with a proteasome inhibitor MG-132 against H82 small cell lung cancer cells and in FIG. 21C, the effects on key target proteins EZH2 and MYC.

Example 11
Effectiveness of Silvestrol in Neuroblastoma Cell Lines In Vitro

The effect of silvestrol on several neuroblastoma cell lines was evaluated. The results are shown in the table below.

Cells
Silvestrol (IC50 nM)
Description

BE(1)N
2.52
N-MYC

IMR32
2.86
N_MYC

SKNCM
20.21

BE(2)C
47.83
N-MYC

Example 12
Identification of G-Quadruplexes in KRAS

As shown in the four annotated transcripts of KRAS in FIG. 22A with different and overlapping 5′UTRs, the minimal/common region of the 5′UTR has two G-quadruplexes (FIG. 22B). They have at least two and up to five G-quadruplex structures (FIG. 22C-F). FIG. 23A shows the Mfold structure of the NRAS 5′UTR, and FIG. 23B compares the KRAS and NRAS transcripts showing a similar density of G-quadruplexes, identifying KRAS as a potential silvestrol target.

Example 13
Effect of Silvestrol on KRAS Protein Levels in PANC1 Cells In Vitro

Similarly to that described in Example 8, silvestrol at 50 nM shows a loss of KRAS expression (FIG. 24A). KRAS has a long T_1/2compared to MYC, and therefore the effect is less pronounced. The in vitro activity of an S6 kinase inhibitor, rapamycin, silvestrol and combinations on PNAC1 and MiaPaca2 cells are shown in FIGS. 24B and 24C, respectively.

Example 14
In Vivo Activity of Silvestrol Against MiaPaca2 Xenografts

FIG. 25 shows the results in mice with MiaPaca2 xenografts when of 0.2 mg/kg silvestrol or vehicle was administered every other day from days 30-60 following tumor implantation. FIG. 25A shows the outcome using fluorescent imaging at 8 weeks; the excised tumors are shown in FIG. 25B; and the tumor volumes in FIG. 25C.

Example 15
In Vivo Activity of Silvestrol Against Small Cell Lung Cancer

FIG. 26 shows the results of a xenograft experiment using small cell lung cancer line NCI-H82 and silvestrol administration. The average tumor volumes and animal weights are shown in the top left and bottom left graphs, respectively, and the data legends corresponding to the animal groups and treatments (dose level, dose regimen and compounds) in the photographs and their legends at the right. In FIG. 27, the results from the same experiment using 0.2 mg/kg and 0.5 mg/kg silvestrol are plotted in the left graph, and the effect on key target proteins at different time points on the right.

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TABLE 1

Detailed summary of T-ALL patient mutations

MYC
NOTCH1 mutation
IL7R mutation
PTEN mutation + deletion
Genetic

ID
translocat
Nucleotide change Predicted prot. lesion
Domain
Nt chg.
Prot. chg.
Domain
Nucleotide change Predicted prot. lesion
subtype

1
t(8; 14) (q24; q11)
—

—

heterozygous deletion
Unknown

2
—
c.7331_7332insCG (heterozygous) p.V2444fs*35
PEST
—

c.[738delGTT; 737_741insCCCGG]
TAL/LMO (SIL-TAL)

(heterozygous) p.P246fs*11

3
—
c.7393delC (heterozygous) p.L2465fs*13
PEST
—

c.388C > T (homozygous) p.R130*
TAL/LMO (SIL-TAL)

c.[5023_5024delTT, 5022_025insCCC](het.) p.S1675fs*8
HD

4
—
c.[7372delC; 7372_7374insGGT] (het.)
PEST
—

heterozygous deletion exon 4-9
TAL/LMO

p.L2458fs*21
HD

(LMO2)

c.4802T > C (heterozygous) p.L1601P

5
—
c.4802T > C (heterozygous) p.L1601P
HD
—

—
HOXA (inv(7))

6
—
c.7510C > T (heterozygous) p.Q2504*
PEST
—

—
TLX3

7
—
C.5229C_5230GinsAGATTCCCTTATGGGACC (heterozygous)
JM
—

—
Unknown

8
—
C.4858_4864TACTACG > CCCGTCC (het.)
HD
—

—
TAL/LMO

p.1620_1622YYG > PDR

(LMO2)

9
—
c.7504C > T (heterozygous) p.Q2502*
PEST
—

—
Unknown

c.5036T > C (heterozygous) p.L1679P
HD

10
—
C.4748_4749insCCCCCCTTATAC (het.)
PY
—

—
Unknown

p.P1583_E1584insPPYT

11
—
c.[4749_4752delGGAG; 4748_4749insC] (het.)
HD
—

—
Unknown

p.E1584del

12
—
c.4732_4737delGTGGTG (heterozygous)
HD
—

—
TAL/LMO

p.V1578 _V1579del
PEST

(LMO2)

c.7462C > T (heterozygous) p.Q2488*

13
—
c. [7545_7548delTGAG;
PEST
—

—
HOXA (CALM-AF10

7545_7546insCTTT; 7552_7553insGAGC] (het.)

14
—
c.7318delG (heterozygous) p.P2439fs*39
PEST
—

—
TLX3

C.4728_4729insTTTCTCTTG (het.)
HD

p.V1576_V1577insFLL

15
—
c.7563G > A (heterozygous) p.W2521*
PEST
—

—
TLX3

16
—
c.7462C > T (heterozygous) p.Q2488*
PEST
—

—
TAL/LMO

c.5077T > A (heterozygous) p.C1693S
HD

(LMO2)

17
—
c.4821_4822insGGATTC (heterozygous)
HD
—

—
TAL/LMO

p.F1607 > LDS

(LMO2)

18
—
c.4802T > C (heterozygous) p.L1601P
HD
—

—
TLX3

19
—
c.4781T > C (heterozygous) p.L1594P
HD
—

—
TLX1

20
—
c.4782_4783insGCC (heterozygous)
HD
—

—
TAL/LMO

p.L1594_R1595insP
HD

(SIL-TAL)

21
—
c.4802T > A (heterozygous) p.L1601Q
HD
—

—
TLX1

22
—
—

C.758T > G
p.V253G
TM
—
Unknown

23
—
—

—

c.697C > T (heterozygous) p.R233*
TLX3

heterozygous deletion

24
—
—

c.749_750insCCCCAGCTTGGATAG
TAL/LMO

(heterozygous) p.G251fs*5
(LMO2)

25
—
—

—

c.295G > T (heterozygous) p.E99*
TAL/LMO

(SIL-TAL)

26
—
—

—

heterozygous deletion exon 1-3
TAL/LMO

(LMO2)

27
—
—

—

—
HOXA (inv(7))

28
—
—

—

—
HOXA (MLL)

29
—
—

—

—
HOXA (MLL)

30
—
—

—

—
TAL/LMO

(SIL-TAL)

31
—
—

—

—
TAL/LMO

(SIL-TAL)

32
—
—

—

—
TAL/LMO

(SIL-TAL)

33
—
—

—

—
TLX3

34
—
—

—

—
TLX1

35
—
—

—

—
TLX1

36
—
—

—

—
Unknown

TABLE 2

In vivo toxicity study of (±)-CR-31-B

2A. Individual body and organ weights.

Body Weight
Liver
Spleen
Left Kidney
Right Kidney

Group
Animal #
(gm)
(gm)
(gm)
(gm)
(gm)

Vehicle Female
1
16.093
0.810
0.060
0.117
0.137

Day 5
2
17.550
0.925
0.060
0.132
0.129

3
18.866
0.965
0.059
0.176
0.192

4
16.826
0.889
0.057
0.149
0.136

Mean
17.334
0.897
0.059
0.144
0.149

Std Dev
1.182
0.066
0.001
0.025
0.029

N
4
4
4
4
4

0.2 mg/kg Female
7
15.962
0.807
0.049
0.108
0.119

Day 5
8
17.217
0.969
0.070
0.133
0.125

9
17.463
0.914
0.086
0.138
0.135

10
16.078
0.843
0.064
0.125
0.125

Mean
16.680
0.883
0.067
0.126
0.126

Std Dev
0.770
0.072
0.015
0.013
0.007

N
4
4
4
4
4

% ChVh
−3.8
−1.6
13.6
−12.5
−15.4

Vehicle Female
5
17.878
0.977
0.063
0.136
0.150

Day 19
6
16.845
0.969
0.062
0.118
0.124

Mean
17.362
0.973
0.063
0.127
0.137

Std Dev
0.730
0.006
0.001
0.013
0.018

N
2
2
2
2
2

0.2 mg/kg Female
11
18.769
1.111
0.081
0.111
0.137

Day 19
12
17.192
0.988
0.048
0.113
0.127

Mean
17.981
1.050
0.065
0.112
0.132

Std Dev
1.115
0.087
0.023
0.001
0.007

N
2
2
2
2
2

% ChVh
3.6
7.9
3.2
−11.8
−3.6

Liver
Spleen
Left Kidney
Right Kidney

Group
Animal #
(% body wt)
(% body wt)
(% body wt)
(% body wt)

Vehicle Female
1
5.03
0.37
0.85
0.85

Day 5
2
5.27
0.34
0.75
0.74

3
5.12
0.31
0.93
1.02

4
5.28
0.34
0.89
0.81

Mean
5.18
0.34
0.86
0.86

Std Dev
0.12
0.02
0.08
0.12

N
4
4
4
4

0.2 mg/kg Female
7
5.06
0.31
0.75
0.75

Day 5
8
5.63
0.41
0.77
0.73

9
5.23
0.49
0.79
0.77

10
5.24
0.40
0.78
0.78

Mean
5.29
0.40
0.77
0.76

Std Dev
0.24
0.07
0.02
0.02

N
4
4
4
4

% ChVh
2.1
17.6
−10.5
−11.6

Vehicle Female
5
5.46
0.35
0.84
0.84

Day 19
6
5.75
0.37
0.70
0.74

Mean
5.61
0.36
0.77
0.79

Std Dev
0.21
0.01
0.10
0.07

N
2
2
2
2

0.2 mg/kg Female
11
5.92
0.43
0.73
0.73

Day 19
12
5.75
0.28
0.66
0.74

Mean
5.84
0.36
0.70
0.74

Std Dev
0.12
0.11
0.05
0.01

N
2
2
2
2

% ChVh
4.1
0.0
−9.1
−6.3

2B. Individual hematology

WBC
NEUT
LYM
MONO
EOS
BASO

Group
Animal#
K/uL
K/uL
K/uL
K/uL
K/uL
K/uL
NEUT %
LYM %
MONO %
EOS %
BASO %

Vehicle Female
1
7.24
0.65
6.33
0.24
0.01
0.01
8.92
87.47
3.38
0.17
0.07

Day 5
2
7.44
1.00
6.30
0.10
0.02
0.01
13.43
84.72
1.41
0.27
0.17

3
6.38
0.75
5.50
0.11
0.01
0.01
11.83
86.13
1.69
0.23
0.11

4
4.52
0.72
3.76
0.03
0.00
0.00
15.88
83.26
0.68
0.11
0.07

Mean
6.40
0.78
5.47
0.12
0.01
0.01
12.52
85.40
1.79
0.20
0.11

Std Dev
1.33
0.15
1.20
0.09
0.01
0.01
2.92
1.81
1.14
0.07
0.05

N
4
4
4
4
4
4
4
4
4
4
4

0.2 mg/kg
7
4.78
1.05
3.64
0.08
0.00
0.00
21.94
76.21
1.77
0.01
0.07

Female
8
6.90
1.69
4.96
0.24
0.01
0.00
24.51
71.86
3.45
0.14
0.04

Day 5
9
4.98
1.40
3.49
0.09
0.00
0.00
28.20
70.06
1.74
0.00
0.00

10
6.96
1.70
5.13
0.12
0.01
0.00
24.44
73.76
1.70
0.10
0.00

Mean
5.91
1.46
4.31
0.13
0.01
0.00
24.77
72.97
2.17
0.06
0.03

Std Dev
1.19
0.31
0.86
0.07
0.01
0.00
2.58
2.63
0.86
0.07
0.03

N
4
4
4
4
4
4
4
4
4
4
4

% ChVh
−7.7
87.2
−21.2
8.3
0.0
−100.0
97.8
−14.6
21.2
−70.0
−72.7

Vehicle Female
5
5.44
0.79
4.51
0.10
0.04
0.01
14.44
82.94
1.76
0.76
0.10

Day 19
6
8.68
1.12
7.43
0.09
0.03
0.01
12.85
85.63
1.06
0.34
0.11

Mean
7.06
0.96
5.97
0.10
0.04
0.01
13.65
84.29
1.41
0.55
0.11

Std Dev
2.29
0.23
2.06
0.01
0.01
0.00
1.12
1.90
0.49
0.30
0.01

N
2
2
2
2
2
2
2
2
2
2
2

0.2 mg/kg Female
11
3.36
0.51
2.80
0.03
0.02
0.00
15.03
83.42
0.91
0.50
0.14

Day 19
12
2.50
0.33
2.12
0.02
0.02
0.00
13.29
84.96
0.95
0.66
0.13

Mean
2.93
0.42
2.46
0.03
0.02
0.00
14.16
84.19
0.93
0.58
0.14

Std Dev
0.61
0.13
0.48
0.01
0.00
0.00
1.23
1.09
0.03
0.11
0.01

N
2
2
2
2
2
2
2
2
2
2
2

% ChVh
−58.5
−56.3
−58.8
−70.0
−50.0
−100.0
3.7
−0.1
−34.0
5.5
27.3

RBC
HGB

MCV
MCH
MCHC

PLT
MPV

Group
Animal#
M/uL
g/dL
HCT %
fL
Pg
g/dL
RDW %
K/uL
fL

Vehicle Female
1
8.47
11.9
39.7
46.9
14.0
30.0
16.0
1343
4.6

Day 5
2
9.19
13.8
46.9
51.0
15.0
29.4
15.8
1097
4.7

3
8.51
13.1
44.3
52.0
15.4
29.6
16.3
839
4.4

4
8.97
13.5
45.4
50.6
15.1
29.7
15.6
809
4.3

Mean
8.79
13.1
44.1
50.1
14.9
29.7
15.9
1022.0
4.5

Std Dev
0.35
0.83
3.11
2.23
0.61
0.25
0.30
250.02
0.18

N
4
4
4
4
4
4
4
4
4

0.2 mg/kg
7
9.31
14.3
48.3
51.9
15.4
29.6
15.6
872
4.3

Female Day 5
8
8.95
13.8
45.1
50.4
15.4
30.6
16.1
673
4.3

9
8.69
13.0
43.9
50.5
15.0
29.6
15.2
676
4.1

10
8.89
13.5
45.0
50.6
15.2
30.0
16.4
682
4.3

Mean
8.96
13.7
45.6
50.9
15.3
30.0
15.8
725.8
4.3

Std Dev
0.26
0.54
1.90
0.70
0.19
0.47
0.53
97.57
0.10

N
4
4
4
4
4
4
4
4
4

% ChVh
1.9
4.4
3.4
1.4
2.5
0.9
−0.6
−29.0
−5.6

Vehicle Female
5
9.02
14.0
43.8
48.6
15.5
32.0
16.3
1216
4.7

Day 19
6
9.06
13.8
44.3
48.9
15.2
31.2
16.1
949
4.4

Mean
9.04
13.9
44.1
48.8
15.4
31.6
16.2
1082.5
4.6

Std Dev
0.03
0.14
0.35
0.21
0.21
0.57
0.14
188.80
0.21

N
2
2
2
2
2
2
2
2
2

0.2 mg/kg Female
11
9.33
13.4
45.9
49.2
14.4
29.2
16.4
990
4.6

Day 19
12
8.70
13.0
42.5
48.8
14.9
30.6
16.2
1403
4.9

Mean
9.02
13.2
44.2
49.0
14.7
29.9
16.3
1196.5
4.8

Std Dev
0.45
0.28
2.40
0.28
0.35
0.99
0.14
292.04
0.21

N
2
2
2
2
2
2
2
2
2

% ChVh
−0.2
−5.0
0.2
0.4
-4.5
-5.4
0.6
10.5
4.3

2C. Bone marrow and spleen cytology

Bone Marrow

Mat
% mat
Pro
% Pro
Total
% T
Mat
% Mat
Prol
% Pro
Total
% T

Animal
myel
myel
myel
myel
myel
myel
ery
ery
ery
ery
Ery
ery

Vehicle #1
124
41.3
28
9.3
152
50.7
57
19.0
29
9.7
86
28.7

Vehicle #2
121
40.3
30
10.0
151
50.3
64
21.3
24
8.0
88
29.3

Vehicle #3
105
35.0
58
19.3
163
54.3
57
19.0
32
10.7
89
29.7

Vehicle #4
115
38.3
46
15.3
161
53.7
47
15.7
26
8.7
73
24.3

Treatment #7
122
40.7
34
11.3
156
52.0
56
18.7
24
8.0
80
26.7

Treatment #8
88
29.3
64
21.3
152
50.7
62
20.7
26
8.7
88
29.3

Treatment #9
120
40.0
52
17.3
172
57.3
45
15.0
22
7.3
67
22.3

Treatment #10
121
40.3
72
24.0
193
64.3
38
12.7
25
8.3
63
21.0

Spleen

Animal
% Lymph
% Macrophage
% Myeloid
% Erythroid
% Plasma
% Mesenchymal

Vehicle #1
92
6
1
1
0
0

Vehicle #2
93
2
5
0
0
0

Vehicle #3
96
1
1
0
0
2

Vehicle #4
97
2
0
0
1
0

Treatment #7
94
2
4
0
0
0

Treatment #8
90
2
7
0
1
0

Treatment #9
90
0
9
1
0
0

Treatment #10
86
2
10
0
0
2

Mat

Total

Animal
myel
Lymph
% Lymph
Plasma
% Plasma
Mast
% Mast
Mega*
Quality*
cell
M:E

Vehicle #1
124
62
20.7
0
0.0
0
0.0
p
a
300
1.8

Vehicle #2
121
61
20.3
0
0.0
0
0.0
p
a
300
1.7

Vehicle #3
105
48
16.0
0
0.0
0
0.0
p
a
300
1.8

Vehicle #4
115
66
22.0
0
0.0
0
0.0
P
a
300
2.2

0.0
0.0

Treatment #7
122
64
21.3
0
0.0
0
0.0
P
a
300
2.0

Treatment #8
88
60
20.0
0
0.0
0
0.0
p
a
300
1.7

Treatment #9
120
61
20.3
0
0.0
0
0.0
p
a
300
2.6

Treatment #10
121
44
14.7
0
0.0
0
0.0

300
3.1

Spleen

Animal
% Lymph
Comment
Total %

Vehicle #1
92

100

Vehicle #2
93

100

Vehicle #3
96

100

Vehicle #4
97
large numbers of pleomorphic rod bacteria
100

in background of smear

Treatment #7
94

100

Treatment #8
90

100

Treatment #9
90

100

Treatment #10
86

100

2D. Individual chemistry

ALP
ALT
AST
GGT
ALB
TP
GLOB
A/G
TBIL
BUN
CRTN

Group
Animal #
U/L
U/L
U/L
U/L
g/dL
g/dL
g/dL
Ratio
mg/d L
mg/d L
mg/dL

Vehicle Female
1
125
22
39
0
2.8
4.5
1.7
1.6
0.2
24
0.1

Day 5
2
115
14
31
0
3.1
4.9
1.8
1.7
0.2
28
0.2

3
122
19
32
0
2.9
4.5
1.6
1.8
0.1
23
0.2

4
133
22
34
0
3.0
4.7
1.7
1.8
0.2
31
0.2

Mean
123.8
19.3
34.0
0.0
3.0
4.7
1.7
1.7
0.18
26.5
0.18

Std
7.46
3.77
3.56
0.00
0.13
0.19
0.08
0.10
0.05
3.70
0.05

Dev

N
4
4
4
4
4
4
4
4
4
4
4

0.2 mg/kg
7
116
26
51
0
3.3
5.1
1.8
1.8
0.2
27
0.2

Female
8
114
20
35
0
3.0
4.8
1.8
1.7
0.2
26
0.2

Day 5
9
123
34
44
0
2.9
4.8
1.9
1.5
0.1
27
0.2

10
144
20
35
0
3.1
4.9
1.8
1.7
0.2
29
0.2

Mean
124.3
25.0
41.3
0.0
3.1
4.9
1.8
1.7
0.18
27.3
0.20

Std
13.72
6.63
7.76
0.00
0.17
0.14
0.05
0.13
0.05
1.26
0.00

Dev

N
4
4
4
4
4
4
4
4
4
4
4

% ChVh

3.3
4.3
5.9
0.0
0.0
3.0
11.1

FoldChVh
1.0
1.3
1.2
NC

Vehicle Female
5
164
20
46
0
3.2
5.1
1.9
1.7
0.1
31
0.2

Day 19
6
193
40
78
0
2.9
4.6
1.7
1.7
0.0
34
0.2

Mean
178.5
30.0
62.0
0.0
3.1
4.9
1.8
1.7
0.05
32.5
0.20

Std Dev
20.51
14.14
22.63
0.00
0.21
0.35
0.14
0.00
0.07
2.12
0.00

N
2
2
2
2
2
2
2
2
2
2
2

0.2 mg/kg Female
11
144
20
33
0
2.9
4.7
1.8
1.6
0.1
29
0.2

Day 19
12
160
22
38
0
2.9
4.7
1.8
1.6
0.1
35
0.2

Mean
152.0
21.0
35.5
0.0
2.9
4.7
1.8
1.6
0.10
32.0
0.20

Std
11.31
1.41
3.54
0.00
0.00
0.00
0.00
0.00
0.00
4.24
0.00

Dev

N
2
2
2
2
2
2
2
2
2
2
2

% ChVh

-6.5
-4.1
0.0
-5.9
100.0
-1.5
0.0

FoldChVh
0.9
0.7
0.6
NC

Animal
CHOL
GLUC
Ca
P
Cl
K
Na
Na/K

Group
#
mg/dL
mg/dL
mg/dL
mg/dL
mEq/L
mEq/L
mEq/L
Ratio

Vehicle Female
1
62
301
7.1
8.1
113
5.7
148
26

Day 5
2
78
287
9.8
7.3
113
3.8
150
39

3
63
307
9.5
7.5
116
4.0
151
38

4
61
273
9.2
9.8
111
4.0
148
37

Mean
66.0
292.0
8.9
8.2
113.3
4.4
149.3
35.0

Std Dev
8.04
15.19
1.22
1.14
2.06
0.89
1.50
6.06

N
4
4
4
4
4
4
4
4

7
68
270
8.9
6.3
116
4.6
152
33

0.2 mg/kg Female
8
66
335
9.0
7.3
113
4.0
147
37

Day 5
9
64
261
9.3
7.5
114
4.4
150
34

10
66
323
9.3
7.0
113
3.9
147
38

Mean
66.0
297.3
9.1
7.0
114.0
4.2
149.0
35.5

Std Dev
1.63
37.17
0.21
0.53
1.41
0.33
2.45
2.38

N
4
4
4
4
4
4
4
4

% ChVh
0.0
1.8
2.2
−14.6
0.6
−4.5
−0.2
1.4

FoldChVh

Vehicle Female
5
74
261
9.4
6.0
116
4.3
148
34

Day 19
6
59
261
9.5
7.5
116
4.1
148
36

Mean
66.5
261.0
9.5
6.8
116.0
4.2
148.0
35.0

Std Dev
10.61
0.00
0.07
1.06
0.00
0.14
0.00
1.41

N
2
2
2
2
2
2
2
2

0.2 mg/kg Female
11
71
254
9.0
9.6
112
3.5
147
42

Day 19
12
59
227
9.4
10.8
117
4.0
149
37

Mean
65.0
240.5
9.2
10.2
114.5
3.8
148.0
39.5

Std Dev
8.49
19.09
0.28
0.85
3.54
0.35
1.41
3.54

N
2
2
2
2
2
2
2
2

% ChVh
−2.3
−7.9
−3.2
50.0
−1.3
−9.5
0.0
12.9

FoldChVh

*p = present a = adequate

TABLE 3A

Motifs and G-quadruplexes in TE down genes.

Gene ID
Gene Name
Translational Efficiency (p-value)
log2 (Translational Efficiency)
rDiff (p-value)

ENSG00000204147
ASAH2B
0.015002357
−1.322460998
1

ENSG00000125827
TMX4
0.004516727
−1.251223509
1

ENSG00000008710
PKD1
0.016462045
−1.049712325
1

ENSG00000182197
EXT1
0.024702029
−0.999952768
1

ENSG00000181027
FKRP
0.016390601
−0.996001717
1

ENSG00000056998
GYG2
0.026501722
−0.929650779
1

ENSG00000124786
SLC35B3
0.023814954
−0.917840885
1

ENSG00000164970
FAM219A
0.012381128
−0.63799892
1

ENSG00000065802
ASB1
0.011120438
−0.632831228
7.24E−02

ENSG00000150995
ITPR1
0.025529346
−0.628260516
1

ENSG00000130669
PAK4
0.02752902
−0.627975797
1

ENSG00000166503
HDGFRP3
0.000273828
−0.608750084
1.19E−02

ENSG00000180730
SHISA2
2.85E−05
−0.608613867
1.93E−02

ENSG00000119844
AFTPH
0.008725735
−0.591675727
1

ENSG00000180035
ZNF48
0.015918146
−0.582772982
1

ENSG00000133056
PIK3C2B
0.016052253
−0.537952135
1

ENSG00000109220
CHIC2
0.018242688
−0.521221308
1.70E−02

ENSG00000127152
BCL11B
5.40E−10
−0.517770746
1.00E−08

ENSG00000140853
NLRC5
0.009461003
−0.515280789
1

ENSG00000034677
RNF19A
0.025744017
−0.483894067
1

ENSG00000105321
CCDC9
0.020946401
−0.480466187
1

ENSG00000151014
CCRN4L
0.007814184
−0.480208055
7.50E−03

ENSG00000123159
GIPC1
0.00645275
−0.478285755
6.90E−03

ENSG00000171791
BCL2
0.008656918
−0.474172722
6.00E−01

ENSG00000065970
FOXJ2
0.017646559
−0.4735107
1

ENSG00000066933
MYO9A
0.008868511
−0.473506657
1

ENSG00000182150
ERCC6L2
0.016924169
−0.466789648
1

ENSG00000100393
EP300
1.18E−05
−0.464539688
1.10E−03

ENSG00000120949
TNFRSF8
0.022812631
−0.437286644
7.40E−03

ENSG00000123575
FAM199X
0.029642368
−0.431235143
2.08E−02

ENSG00000179195
ZNF664
0.005477293
−0.42685597
1

ENSG00000166024
R3HCC1L
0.024332543
−0.416140766
1

ENSG00000123066
MED13L
4.79E−05
−0.415941737
2.20E−08

ENSG00000145349
CAMK2D
0.021359574
−0.408237368
7.82E−02

ENSG00000110218
PANX1
0.005542647
−0.39874583
2.59E−02

ENSG00000003402
CFLAR
0.024657096
−0.397685039
4.71E−02

ENSG00000164168
TMEM184C
0.015050183
−0.397412646
2.50E−08

ENSG00000169018
FEM1B
0.01910054
−0.397020738
3.00E−04

ENSG00000007168
PAFAH1B1
0.000466042
−0.383179082
9.80E−03

ENSG00000169967
MAP3K2
0.013056576
−0.377048905
6.60E−03

ENSG00000162889
MAPKAPK2
0.016286083
−0.352699883
5.49E−01

ENSG00000063978
RNF4
0.002157553
−0.344201177
1.28E−02

ENSG00000064490
RFXANK
0.015800837
−0.324746409
3.00E−04

ENSG00000100105
PATZ1
0.00652701
−0.324460116
3.10E−03

ENSG00000103502
CDIPT
0.021406946
−0.323954264
1.43E−01

ENSG00000095380
NANS
0.027123309
−0.321819229
5.39E−02

ENSG00000160917
CPSF4
0.016200762
−0.319405125
1.70E−03

ENSG00000153561
RMND5A
0.029110593
−0.311729374
2.03E−01

ENSG00000108510
MED13
0.005034555
−0.293870753
1.60E−03

ENSG00000112531
QKI
0.00269178
−0.29125342
8.40E−03

ENSG00000163349
HIPK1
0.020020123
−0.282659771
2.00E−04

ENSG00000111885
MAN1A1
0.010654006
−0.274580872
2.24E−02

ENSG00000048405
ZNF800
0.020652909
−0.271097499
3.00E−08

ENSG00000115419
GLS
0.000197719
−0.269875671
4.00E−04

ENSG00000182831
C16orf72
0.00375696
−0.255255837
1.07E−01

ENSG00000131507
NDF1P1
0.004173323
−0.242895723
6.80E−03

ENSG00000134602
MST4
0.003080229
−0.242407773
1.05E−02

ENSG00000159692
CTBP1
0.006057739
−0.241648156
5.00E−03

ENSG00000106609
TMEM248
0.005316307
−0.23621242
2.90E−07

ENSG00000152684
PELO
0.01293572
−0.236131973
7.82E−02

ENSG00000134954
ETS1
1.27E−05
−0.232324455
5.70E−09

ENSG00000140332
TLE3
0.001343794
−0.227829431
2.00E−08

ENSG00000169905
TOR1AIP2
0.025144824
−0.223803399
7.00E−04

ENSG00000149480
MTA2
2.64E−05
−0.22354576
6.00E−09

ENSG00000105329
TGFB1
0.015301045
−0.221315351
2.00E−04

ENSG00000131504
DIAPH1
0.005406879
−0.213577391
2.00E−04

ENSG00000138795
LEF1
1.60E−06
−0.210659864
1.00E−09

ENSG00000106290
TAF6
0.014175182
−0.210235711
5.00E−04

ENSG00000137845
ADAM10
0.012053048
−0.208903322
9.00E−10

ENSG00000136878
USP20
0.019165529
−0.206602358
2.00E−08

ENSG00000172292
CERS6
0.029552171
−0.205124483
1.00E−09

ENSG00000135932
CAB39
0.019948395
−0.200243436
1.00E−08

ENSG00000118816
CCNI
0.001528498
−0.189161037
6.90E−07

ENSG00000151465
CDC123
0.007301
−0.184803611
3.23E−01

ENSG00000140262
TCF12
0.025334533
−0.184064816
2.00E−10

ENSG00000100796
SMEK1
0.021404696
−0.176469607
1.00E−11

ENSG00000112306
RPS12
0.029227861
−0.173199482
1.13E−01

ENSG00000105063
PPP6R1
0.029786388
−0.157573098
1.00E−10

ENSG00000120727
PAIP2
0.010801093
−0.157320231
5.59E−01

ENSG00000152601
MBNL1
0.00777836
−0.152181062
2.00E−11

ENSG00000088325
TPX2
0.000751758
−0.147886462
4.00E−13

ENSG00000171310
CHST11
0.004536717
−0.14604981
1.20E−07

ENSG00000158985
CDC42SE2
0.027991366
−0.145160094
8.00E−08

ENSG00000184007
PTP4A2
0.00039459
−0.142942918
1.50E−07

ENSG00000153310
FAM49B
0.007506383
−0.139159484
2.00E−04

ENSG00000121083
DYNLL2
0.02989098
−0.137797441
1.00E−03

ENSG00000078369
GNB1
0.011642786
−0.133797709
5.00E−04

ENSG00000125743
SNRPD2
0.024903253
−0.131448444
2.38E−01

ENSG00000110651
CD81
0.010480682
−0.130640591
1.00E−04

ENSG00000077312
SNRPA
0.023537735
−0.127819876
1.26E−01

ENSG00000125970
RALY
0.004001428
−0.112279678
3.64E−02

ENSG00000169764
UGP2
0.027598388
−0.103615488
1.60E−03

ENSG00000138668
HNRNPD
0.003261874
−0.098862205
2.40E−07

ENSG00000167978
SRRM2
0.027585188
−0.081656945
1.00E−04

TABLE 3B

TE Down genes with 9-mer GC-rich motif

Gene ID
Gene Name
Translational Efficiency (p-value)
log2 (Translational Efficiency)
rDiff (p-value)

ENSG00000142530
FAM71E1
0.007231579
−13.06577528
1

ENSG00000164877
MICALL2
0.00343177
−13.04340083
1

ENSG00000205002
AARD
0.005983799
−12.57393172
1

ENSG00000096264
NCR2
0.004901353
−12.43253148
1

ENSG00000104881
PPP1R13L
0.01002069
−1.405330178
1

ENSG00000154016
GRAP
0.010299775
−1.388227224
1

ENSG00000025434
NR1H3
0.009825261
−1.378487187
1

ENSG00000204147
ASAH2B
0.015002357
−1.322460998
1

ENSG00000111664
GNB3
0.016841552
−1.309465795
1

ENSG00000154783
FGD5
0.010083869
−1.258941532
1

ENSG00000125827
TMX4
0.004516727
−1.251223509
1

ENSG00000139112
GABARAPL1
0.008844095
−1.233522978
1

ENSG00000162065
TBC1D24
0.005127762
−1.23071089
1

ENSG00000102265
TIMP1
0.019522742
−1.114778075
1

ENSG00000008710
PKD1
0.016462045
−1.049712325
1

ENSG00000182986
ZNF320
0.027309984
−1.003743356
1

ENSG00000106829
TLE4
0.000832033
−1.003696096
1

ENSG00000182197
EXT1
0.024702029
−0.999952768
1

ENSG00000181027
FKRP
0.016390601
−0.996001717
1

ENSG00000064687
ABCA7
0.01073148
−0.991801368
1

ENSG00000056998
GYG2
0.026501722
−0.929650779
1

ENSG00000124786
SLC35B3
0.023814954
−0.917840885
1

ENSG00000075399
VPS9D1
0.01039008
−0.829631073
1

ENSG00000172732
MUS81
0.000200214
−0.721332975
1.05E−01

ENSG00000055208
TAB2
0.005417389
−0.647025741
1

ENSG00000164970
FAM219A
0.012381128
−0.63799892
1

ENSG00000065802
ASB1
0.011120438
−0.632831228
7.24E−02

ENSG00000150995
ITPR1
0.025529346
−0.628260516
1

ENSG00000130669
PAK4
0.02752902
−0.627975797
1

ENSG00000112394
SLC16A10
0.018925329
−0.615544597
1

ENSG00000166503
HDGFRP3
0.000273828
−0.608750084
1.19E−02

ENSG00000180730
SHISA2
2.85E−05
−0.608613867
1.93E−02

ENSG00000176994
SMCR8
0.003428912
−0.604582332
1

ENSG00000204348
DOM3Z
0.026501738
−0.595853393
1

ENSG00000152127
MGAT5
0.000966439
−0.592236096
1.04E−01

ENSG00000119844
AFTPH
0.008725735
−0.591675727
1

ENSG00000180035
ZNF48
0.015918146
−0.582772982
1

ENSG00000132879
FBXO44
0.011714393
−0.538058958
1.10E−01

ENSG00000133056
PIK3C2B
0.016052253
−0.537952135
1

ENSG00000137822
TUBGCP4
0.017824276
−0.534568492
3.06E−02

ENSG00000109220
CHIC2
0.018242688
−0.521221308
1.70E−02

ENSG00000127152
BCL11B
5.40E−10
−0.517770746
1.00E−08

ENSG00000140853
NLRC5
0.009461003
−0.515280789
1

ENSG00000135049
AGTPBP1
0.005676581
−0.500916234
1

ENSG00000141873
SLC39A3
0.00107034
−0.49572766
1

ENSG00000034677
RNF19A
0.025744017
−0.483894067
1

ENSG00000105321
CCDC9
0.020946401
−0.480466187
1

ENSG00000151014
CCRN4L
0.007814184
−0.480208055
7.50E−03

ENSG00000123159
GIPC1
0.00645275
−0.478285755
6.90E−03

ENSG00000102384
CENPI
0.021332262
−0.475386617
5.97E−02

ENSG00000171791
BCL2
0.008656918
−0.474172722
6.00E−01

ENSG00000065970
FOXJ2
0.017646559
−0.4735107
1

ENSG00000066933
MYO9A
0.008868511
−0.473506657
1

ENSG00000120709
FAM53C
0.016598125
−0.471476024
2.15E−01

ENSG00000182150
ERCC6L2
0.016924169
−0.466789648
1

ENSG00000100393
EP300
1.18E−05
−0.464539688
1.10E−03

ENSG00000143479
DYRK3
0.013602392
−0.462587869
3.58E−02

ENSG00000136770
DNAJC1
0.019563299
−0.448209599
2.70E−03

ENSG00000100354
TNRC6B
0.002839187
−0.444181516
1

ENSG00000120949
TNFRSF8
0.022812631
−0.437286644
7.40E−03

ENSG00000154370
TRIM11
0.010190424
−0.431525912
3.01E−04

ENSG00000111450
STX2
0.024088299
−0.4313432
3.52E−01

ENSG00000123575
FAM199X
0.029642368
−0.431235143
2.08E−02

ENSG00000179195
ZNF664
0.005477293
−0.42685597
1

ENSG00000165244
ZNF367
0.002786549
−0.420795786
5.50E−03

ENSG00000166024
R3HCC1L
0.024332543
−0.416140766
1

ENSG00000123066
MED13L
4.79E−05
−0.415941737
2.20E−08

ENSG00000198924
DCLRE1A
0.011556077
−0.415137858
1.40E−02

ENSG00000143570
SLC39A1
0.002068007
−0.414472027
1.43E−01

ENSG00000145349
CAMK2D
0.021359574
−0.408237368
7.82E−02

ENSG00000110218
PANX1
0.005542647
−0.39874583
2.59E−02

ENSG00000003402
CFLAR
0.024657096
−0.397685039
4.71E−02

ENSG00000164168
TMEM184C
0.015050183
−0.397412646
2.50E−08

ENSG00000169018
FEM1B
0.01910054
−0.397020738
3.00E−04

ENSG00000168092
PAFAH1B2
0.008647229
−0.388340708
3.82E−02

ENSG00000178209
PLEC
0.015088771
−0.385965026
1

ENSG00000007168
PAFAH1B1
0.000466042
−0.383179082
9.80E−03

ENSG00000179912
R3HDM2
0.018146798
−0.377340675
9.00E−02

ENSG00000169967
MAP3K2
0.013056576
−0.377048905
6.60E−03

ENSG00000157600
TMEM164
0.010364528
−0.374375608
3.56E−01

ENSG00000213654
GPSM3
0.018261413
−0.371438487
1.02E−01

ENSG00000137310
TCF19
0.006852109
−0.371039482
2.27E−02

ENSG00000126215
XRCC3
0.022817606
−0.355664276
1.50E−03

ENSG00000033170
FUT8
0.006226232
−0.355628717
6.00E−04

ENSG00000162889
MAPKAPK2
0.016286083
−0.352699883
5.49E−01

ENSG00000063978
RNF4
0.002157553
−0.344201177
1.28E−02

ENSG00000177542
SLC25A22
0.013143394
−0.338628583
1.17E−01

ENSG00000132388
UBE2G1
0.000234936
−0.336746882
6.21E−03

ENSG00000170340
B3GNT2
0.004125239
−0.332264603
2.00E−02

ENSG00000064490
RFXANK
0.015800837
−0.324746409
3.00E−04

ENSG00000100105
PATZ1
0.00652701
−0.324460116
3.10E−03

ENSG00000103502
CDIPT
0.021406946
−0.323954264
1.43E−01

ENSG00000095380
NANS
0.027123309
−0.321819229
5.39E−02

ENSG00000160917
CPSF4
0.016200762
−0.319405125
1.70E−03

ENSG00000158435
CNOT11
0.001841931
−0.314941827
8.69E−02

ENSG00000153561
RMND5A
0.029110593
−0.311729374
2.03E−01

ENSG00000102858
MGRN1
0.02977034
−0.309624822
1.40E−02

ENSG00000058668
ATP2B4
0.000680955
−0.302809666
1.00E−09

ENSG00000143418
CERS2
5.25E−06
−0.30206333
2.77E−01

ENSG00000089009
RPL6
0.004810696
−0.297683768
3.87E−01

ENSG00000196155
PLEKHG4
0.015595222
−0.295432913
1.00E−04

ENSG00000108510
MED13
0.005034555
−0.293870753
1.60E−03

ENSG00000112531
QKI
0.00269178
−0.29125342
8.40E−03

ENSG00000053770
AP5M1
0.011896453
−0.283753407
1.00E−02

ENSG00000163349
HIPK1
0.020020123
−0.282659771
2.00E−04

ENSG00000122257
RBBP6
0.000891329
−0.280964053
1.25E−09

ENSG00000017483
SLC38A5
0.015966238
−0.280122734
2.30E−03

ENSG00000171522
PTGER4
0.002288634
−0.274827847
2.40E−07

ENSG00000111885
MAN1A1
0.010654006
−0.274580872
2.24E−02

ENSG00000048405
ZNF800
0.020652909
−0.271097499
3.00E−08

ENSG00000115419
GLS
0.000197719
−0.269875671
4.00E−04

ENSG00000112851
E RBB2IP
0.005962767
−0.26900197
3.00E−04

ENSG00000105287
PRKD2
0.018773736
−0.262403451
1.25E−02

ENSG00000182831
C16or172
0.00375696
−0.255255837
1.07E−01

ENSG00000007968
E2F2
0.009479782
−0.24865366
4.20E−03

ENSG00000100225
FBXO7
0.00882935
−0.246942196
1.08E−02

ENSG00000171552
BCL2L1
0.00522943
−0.245325394
6.32E−02

ENSG00000131507
NDFIP1
0.004173323
−0.242895723
6.80E−03

ENSG00000090621
PABPC4
0.000282201
−0.242834811
1.71E−02

ENSG00000134602
MST4
0.003080229
−0.242407773
1.05E−02

ENSG00000159692
CTBP1
0.006057739
−0.241648156
5.00E−03

ENSG00000133657
ATP13A3
0.021301072
−0.237052311
1.00E−10

ENSG00000106609
TMEM248
0.005316307
−0.23621242
2.90E−07

ENSG00000152684
PELO
0.01293572
−0.236131973
7.82E−02

ENSG00000104325
DECR1
0.01371001
−0.232829844
1.19E−02

ENSG00000134954
ETS1
1.27E−05
−0.232324455
5.70E−09

ENSG00000140332
TLE3
0.001343794
−0.227829431
2.00E−08

ENSG00000147140
NONO
0.003389405
−0.227308156
3.57E−02

ENSG00000169905
TOR1AIP2
0.025144824
−0.223803399
7.00E−04

ENSG00000149480
MTA2
2.64E−05
−0.22354576
6.00E−09

ENSG00000136997
MYC
0.000130485
−0.222358961
3.00E−08

ENSG00000105329
TGFB1
0.015301045
−0.221315351
2.00E−04

ENSG00000107485
GATA3
0.025270056
−0.218676008
1.34E−02

ENSG00000171858
RPS21
0.00024084
−0.216003759
5.41E−03

ENSG00000131504
DIAPH1
0.005406879
−0.213577391
2.00E−04

ENSG00000138795
LEF1
1.60E−06
−0.210659864
1.00E−09

ENSG00000106290
TAF6
0.014175182
−0.210235711
5.00E−04

ENSG00000137845
ADAM10
0.012053048
−0.208903322
9.00E−10

ENSG00000136878
USP20
0.019165529
−0.206602358
2.00E−08

ENSG00000174579
MSL2
0.027763257
−0.205275001
5.00E−04

ENSG00000172292
CERS6
0.029552171
−0.205124483
1.00E−09

ENSG00000125691
RPL23
0.004476603
−0.201854357
1.43E−02

ENSG00000135932
CAB39
0.019948395
−0.200243436
1.00E−08

ENSG00000155508
CNOT8
0.026465866
−0.200101165
6.78E−02

ENSG00000108578
BLMH
0.011959202
−0.198123991
1.66E−01

ENSG00000118816
CCNI
0.001528498
−0.189161037
6.90E−07

ENSG00000101972
STAG2
0.001047325
−0.187270211
7.00E−04

ENSG00000151465
CDC123
0.007301
−0.184803611
3.23E−01

ENSG00000140262
TCF12
0.025334533
−0.184064816
2.00E−10

ENSG00000159216
RUNX1
0.004534671
−0.177621274
5.20E−03

ENSG00000100796
SMEK1
0.021404696
−0.176469607
1.00E−11

ENSG00000143889
HNRPLL
0.02829111
−0.174975752
1.60E−03

ENSG00000112306
RPS12
0.029227861
−0.173199482
1.13E−01

ENSG00000108424
KPNB1
8.66E−05
−0.171777065
2.00E−11

ENSG00000085117
CD82
0.001401537
−0.168060459
2.70E−03

ENSG00000111371
SLC38A1
0.006852608
−0.165827185
3.43E−02

ENSG00000099800
TIMM13
0.01109652
−0.165570746
8.64E−02

ENSG00000105063
PPP6R1
0.029786388
−0.157573098
1.00E−10

ENSG00000120727
PAIP2
0.010801093
−0.157320231
5.59E−01

ENSG00000109685
WHSC1
0.0222009
−0.153361985
1.00E−11

ENSG00000152601
MBNL1
0.00777836
−0.152181062
2.00E−11

ENSG00000197771
MCMBP
0.0158736
−0.149779012
5.90E−03

ENSG00000088325
TPX2
0.000751758
−0.147886462
4.00E−13

ENSG00000171310
CHST11
0.004536717
−0.14604981
1.20E−07

ENSG00000158985
CDC42SE2
0.027991366
−0.145160094
8.00E−08

ENSG00000184007
PTP4A2
0.00039459
−0.142942918
1.50E−07

ENSG00000153310
FAM49B
0.007506383
−0.139159484
2.00E−04

ENSG00000121083
DYNLL2
0.02989098
−0.137797441
1.00E−03

ENSG00000078369
GNB1
0.011642786
−0.133797709
5.00E−04

ENSG00000125743
SNRPD2
0.024903253
−0.131448444
2.38E−01

ENSG00000110651
CD81
0.010480682
−0.130640591
1.00E−04

ENSG00000077312
SNRPA
0.023537735
−0.127819876
1.26E−01

ENSG00000125970
RALY
0.004001428
−0.112279678
3.64E−02

ENSG00000186468
RPS23
0.008328741
−0.104395342
5.03E−01

ENSG00000169764
UGP2
0.027598388
−0.103615488
1.60E−03

ENSG00000138668
HNRNPD
0.003261874
−0.098862205
2.40E−07

ENSG00000167978
SRRM2
0.027585188
−0.081656945
1.00E−04

TABLE 3C

TE down genes with G-Quadruplex structure

Gene ID
Gene Name
Translational Efficiency (p-value)
log2(Translational Efficiency)
rDiff (p-value)

ENSG00000127152
BCL11B
5.40E−10
−0.517770746
1.00E−08

ENSG00000100393
EP300
1.18E−05
−0.464539688
1.10E−03

ENSG00000149480
MTA2
2.64E−05
−0.22354576
6.00E−09

ENSG00000180730
SHISA2
2.85E−05
−0.608613867
1.93E−02

ENSG00000123066
MED13L
4.79E−05
−0.415941737
2.20E−08

ENSG00000132388
UBE2G1
0.000234936
−0.336746882
6.21E−03

ENSG00000166503
HDGFRP3
0.000273828
−0.608750084
1.19E−02

ENSG00000090621
PABPC4
0.000282201
−0.242834811
1.71E−02

ENSG00000184007
PTP4A2
0.00039459
−0.142942918
1.50E−07

ENSG00000007168
PAFAH1B1
0.000466042
−0.383179082
9.80E−03

ENSG00000058668
ATP2B4
0.000680955
−0.302809666
1.00E−09

ENSG00000101972
STAG2
0.001047325
−0.187270211
7.00E−04

ENSG00000109654
TRIM2
0.001320775
−2.146623909
1

ENSG00000140332
TLE3
0.001343794
−0.227829431
2.00E−08

ENSG00000063978
RNF4
0.002157553
−0.344201177
1.28E−02

ENSG00000171522
PTGER4
0.002288634
−0.274827847
2.40E−07

ENSG00000112531
QKI
0.00269178
−0.29125342
8.40E−03

ENSG00000100354
TNRC6B
0.002839187
−0.444181516
1

ENSG00000182831
C16orf72
0.00375696
−0.255255837
1.07E−01

ENSG00000131507
NDFIP1
0.004173323
−0.242895723
6.80E−03

ENSG00000171310
CHST11
0.004536717
−0.14604981
1.20E−07

ENSG00000108510
MED13
0.005034555
−0.293870753
1.60E−03

ENSG00000162065
TBC1D24
0.005127762
−1.23071089
1

ENSG00000106609
TMEM248
0.005316307
−0.23621242
2.90E−07

ENSG00000131504
DIAPH1
0.005406879
−0.213577391
2.00E−04

ENSG00000110218
PANX1
0.005542647
−0.39874583
2.59E−02

ENSG00000123159
GIPC1
0.00645275
−0.478285755
6.90E−03

ENSG00000100105
PATZ1
0.00652701
−0.324460116
3.10E−03

ENSG00000153310
FAM49B
0.007506383
−0.139159484
2.00E−04

ENSG00000152601
MBNL1
0.00777836
−0.152181062
2.00E−11

ENSG00000151014
CCRN4L
0.007814184
−0.480208055
7.50E−03

ENSG00000168092
PAFAH1B2
0.008647229
−0.388340708
3.82E−02

ENSG00000119844
AFTPH
0.008725735
−0.591675727
1

ENSG00000139112
GABARAPL1
0.008844095
−1.233522978
1

ENSG00000066933
MYO9A
0.008868511
−0.473506657
1

ENSG00000120727
PAIP2
0.010801093
−0.157320231
5.59E−01

ENSG00000078369
GNB1
0.011642786
−0.133797709
5.00E−04

ENSG00000137845
ADAM10
0.012053048
−0.208903322
9.00E−10

ENSG00000169967
MAP3K2
0.013056576
−0.377048905
6.60E−03

ENSG00000177542
SLC25A22
0.013143394
−0.338628583
1.17E−01

ENSG00000106290
TAF6
0.014175182
−0.210235711
5.00E−04

ENSG00000105329
TGFB1
0.015301045
−0.221315351
2.00E−04

ENSG00000064490
RFXANK
0.015800837
−0.324746409
3.00E−04

ENSG00000180035
ZNF48
0.015918146
−0.582772982
1

ENSG00000160917
CPSF4
0.016200762
−0.319405125
1.70E−03

ENSG00000162889
MAPKAPK2
0.016286083
−0.352699883
5.49E−01

ENSG00000181027
FKRP
0.016390601
−0.996001717
1

ENSG00000065970
FOXJ2
0.017646559
−0.4735107
1

ENSG00000137822
TUBGCP4
0.017824276
−0.534568492
3.06E−02

ENSG00000109220
CHIC2
0.018242688
−0.521221308
1.70E−02

ENSG00000136878
USP20
0.019165529
−0.206602358
2.00E−08

ENSG00000163349
HIPK1
0.020020123
−0.282659771
2.00E−04

ENSG00000048405
ZNF800
0.020652909
−0.271097499
3.00E−08

ENSG00000145349
CAMK2D
0.021359574
−0.408237368
7.82E−02

ENSG00000100796
SMEK1
0.021404696
−0.176469607
1.00E−11

ENSG00000103502
CDIPT
0.021406946
−0.323954264
1.43E−01

ENSG00000124786
SLC35B3
0.023814954
−0.917840885
1

ENSG00000150995
ITPR1
0.025529346
−0.628260516
1

ENSG00000034677
RNF19A
0.025744017
−0.483894067
1

ENSG00000056998
GYG2
0.026501722
−0.929650779
1

ENSG00000204348
DOM3Z
0.026501738
−0.595853393
1

ENSG00000095380
NANS
0.027123309
−0.321819229
5.39E−02

ENSG00000130669
PAK4
0.02752902
−0.627975797
1

ENSG00000167978
SRRM2
0.027585188
−0.081656945
1.00E−04

ENSG00000112306
RPS12
0.029227861
−0.173199482
1.13E−01

ENSG00000172292
CERS6
0.029552171
−0.205124483
1.00E−09

ENSG00000102858
MGRN1
0.02977034
−0.309624822
1.40E−02

ENSG00000105063
PPP6R1
0.029786388
−0.157573098
1.00E−10

ENSG00000121083
DYNLL2
0.02989098
−0.137797441
1.00E−03

TABLE 4

rDiff positive genes have significant changes in ribosome footprint distribution

Gene ID
Gene Name
rDiff (p-value)
Translational Efficiency (p-value)
log2(Translational Efficiency)

ENSG00000002822
MAD1L1
1.70E−07
0.758278428
−0.03032717

ENSG00000003056
M6PR
8.05E−04
0.341786644
−0.06800052

ENSG00000004700
RECQL
1.00E−08
0.598214663
−0.04903859

ENSG00000004779
NDUFAB1
5.26E−06
0.902185935
0.006429888

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000006114
SYNRG
2.00E−09
0.411165702
0.079008553

ENSG00000008952
SEC62
9.90E−07
0.412197652
0.074389117

ENSG00000009307
CSDE1
5.60E−07
0.282559234
−0.043586952

ENSG00000009335
UBE3C
7.00E−08
0.96703173
0.005178317

ENSG00000009790
TRAF3IP3
2.00E−04
0.932693262
0.007653676

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000010810
FYN
4.02E−04
0.194054982
−0.146493062

ENSG00000011295
TTC19
3.00E−04
0.726452954
0.048391976

ENSG00000011376
LARS2
6.02E−04
0.269847002
−0.142543886

ENSG00000013810
TACC3
2.00E−09
0.886452126
−0.009226853

ENSG00000018699
TTC27
3.00E−04
0.640010253
−0.057075791

ENSG00000021355
SERPINB1
4.00E−04
0.866004942
−0.014203345

ENSG00000021762
OSBPL5
7.01E−04
0.905417327
−0.030769757

ENSG00000027697
IFNGR1
4.00E−04
0.409322091
0.099560346

ENSG00000030066
NUP160
1.00E−11
0.645030987
−0.030045128

ENSG00000030419
IKZF2
3.00E−04
0.413365119
−0.055123312

ENSG00000031698
SARS
2.00E−04
0.872730663
0.011917

ENSG00000033030
ZCCHC8
6.10E−08
0.867990166
−0.021717099

ENSG00000033170
FUT8
6.00E−04
0.006226232
−0.355628717

ENSG00000033178
UBA6
4.00E−04
0.07871533
0.184240847

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000036257
CUL3
3.00E−04
0.568119382
0.048886832

ENSG00000038210
PI4K2B
1.01E−04
0.689067203
0.060060784

ENSG00000038219
BOD1L1
1.00E−04
0.003376816
0.278967432

ENSG00000038358
EDC4
3.00E−04
0.449660549
0.070646944

ENSG00000039123
SKIV2L2
5.00E−08
0.397584419
0.067295718

ENSG00000043462
LCP2
1.00E−04
0.236691265
−0.074243034

ENSG00000047315
POLR2B
9.04E−04
0.311086732
0.072452266

ENSG00000047410
TPR
2.00E−11
0.045762118
0.103472955

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000048740
CELF2
8.00E−04
0.039583811
0.136650125

ENSG00000049618
ARID1B
1.00E−04
0.385309666
0.127414641

ENSG00000051523
CYBA
1.00E−04
0.816434248
0.0204381

ENSG00000052841
TTC17
9.01E−04
0.972969728
0.004383509

ENSG00000054654
SYNE2
9.00E−09
0.143319349
−0.17547751

ENSG00000055044
NOP58
1.00E−11
0.905915474
−0.006508419

ENSG00000055130
CUL1
2.00E−04
0.24134893
−0.116033963

ENSG00000055163
CYFIP2
6.00E−13
0.757974081
−0.02427969

ENSG00000055483
USP36
2.00E−10
0.857880476
0.014047197

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000058668
ATP2B4
1.00E−09
0.000680955
−0.302809666

ENSG00000058729
RIOK2
1.00E−09
0.452540408
0.12495794

ENSG00000059573
ALDH18A1
4.00E−08
0.254939161
−0.109183666

ENSG00000060069
CTDP1
1.00E−04
0.606500761
−0.103959418

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000060339
CCAR1
1.00E−04
0.526971388
0.044049323

ENSG00000060491
OGFR
6.00E−04
0.881572577
−0.018437371

ENSG00000062650
WAPAL
8.00E−04
0.019004475
−0.211592796

ENSG00000062822
POLD1
1.00E−04
0.881523419
−0.010752676

ENSG00000063245
EPN1
6.00E−04
0.095672127
−0.260058118

ENSG00000064115
TM7SF3
3.00E−04
0.921247137
0.007233323

ENSG00000064419
TNPO3
1.00E−04
0.030219393
−0.182349237

ENSG00000064490
RFXANK
3.00E−04
0.015800837
−0.324746409

ENSG00000065150
IPO5
1.00E−04
0.241050243
0.063914843

ENSG00000065328
MCM10
3.00E−08
0.796034459
−0.019990672

ENSG00000065357
DGKA
7.00E−04
0.601907834
−0.04235016

ENSG00000065526
SPEN
1.00E−04
0.859973887
−0.020485515

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000066084
DIP2B
2.20E−08
0.728581353
0.041530278

ENSG00000066279
ASPM
2.00E−09
0.013635649
0.181712013

ENSG00000066654
THUMPD1
1.00E−04
0.066318449
0.218332022

ENSG00000067082
KLF6
6.00E−04
0.873448029
0.015089776

ENSG00000067167
TRAM1
1.80E−07
0.785985329
−0.016953438

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000067596
DHX8
2.00E−08
0.577229448
0.056415372

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000068796
KIF2A
1.00E−04
0.056041279
0.123499472

ENSG00000070756
PABPC1
1.00E−07
0.067231582
−0.133311245

ENSG00000071054
MAP4K4
3.00E−10
0.191479972
−0.114359829

ENSG00000071127
WDR1
1.00E−08
0.661342679
−0.016553317

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000071626
DAZAP1
5.20E−07
0.060128417
−0.110195121

ENSG00000071894
CPSF1
1.00E−04
0.292670446
−0.087303379

ENSG00000072062
PRKACA
5.00E−04
0.823686793
−0.022935317

ENSG00000072310
SREBF1
1.00E−04
0.744899078
−0.026352209

ENSG00000072364
AFF4
4.01E−04
0.18444246
−0.147821651

ENSG00000072778
ACADVL
2.01E−04
0.634381953
0.052306846

ENSG00000073060
SCARB1
4.00E−04
0.444106259
−0.124760329

ENSG00000073614
KDM5A
7.00E−04
0.292729244
−0.104574461

ENSG00000074370
ATP2A3
1.00E−04
0.51081004
−0.034487857

ENSG00000074603
DPP8
1.09E−06
0.371935225
−0.109929668

ENSG00000074695
LMAN1
6.00E−04
0.136972912
0.109603097

ENSG00000074755
ZZEF1
4.01E−04
0.145270305
0.179883886

ENSG00000075415
SLC25A3
3.30E−07
0.062332659
−0.064744845

ENSG00000075539
FRYL
1.00E−04
0.128443961
0.156722872

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000076108
BAZ2A
1.00E−04
0.708000473
−0.042895235

ENSG00000076770
MBNL3
2.60E−07
0.135662004
−0.159547551

ENSG00000077097
TOP2B
1.00E−04
0.84957972
0.01045839

ENSG00000077232
DNAJC10
2.00E−04
0.043053807
−0.322931196

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000078674
PCM1
5.00E−11
0.600752059
−0.058335335

ENSG00000078687
TNRC6C
3.00E−04
0.332794972
−0.148534844

ENSG00000079313
REXO1
7.00E−04
0.723402497
−0.050607046

ENSG00000079432
CIC
8.00E−04
0.820970963
−0.041443313

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000080345
RIF1
3.00E−11
0.722609171
0.022548991

ENSG00000080815
PSEN1
1.50E−07
0.468385762
−0.105188191

ENSG00000080986
NDC80
4.00E−04
0.202768868
0.097858575

ENSG00000081019
RSBN1
8.00E−04
0.864427786
−0.025477267

ENSG00000081237
PTPRC
7.00E−04
0.015733814
0.122576702

ENSG00000081791
KIAA0141
9.00E−04
0.905406058
−0.017374448

ENSG00000082212
ME2
8.00E−04
0.795777072
−0.028699073

ENSG00000082516
GEMIN5
1.00E−04
0.382720363
0.09923243

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−0.205302853

ENSG00000082898
XPO1
1.00E−11
0.026533538
−0.106116515

ENSG00000083312
TNPO1
8.00E−04
0.96323084
0.002633087

ENSG00000083642
PDS5B
6.00E−04
0.586150567
0.042212365

ENSG00000083845
RPS5
3.02E−04
0.290962665
−0.089607269

ENSG00000083857
FAT1
2.07E−09
0.602892898
−0.038812678

ENSG00000084093
REST
1.00E−09
0.221405653
−0.118069779

ENSG00000084207
GSTP1
8.00E−04
0.028975686
0.078499851

ENSG00000084733
RAB10
7.00E−08
0.078220422
−0.136343032

ENSG00000084774
CAD
2.00E−08
0.242515439
0.087577807

ENSG00000086102
NFX1
7.00E−04
0.176154723
0.162273705

ENSG00000086504
MRPL28
1.00E−04
0.056394
−0.151444666

ENSG00000086758
HUWE1
2.40E−11
0.464534104
−0.039863394

ENSG00000087087
SRRT
1.00E−10
0.966692349
0.001824104

ENSG00000087365
SF3B2
1.00E−04
0.108200543
0.071832895

ENSG00000087460
GNAS
3.00E−10
0.461136397
−0.032870857

ENSG00000088247
KHSRP
2.00E−04
0.673716802
−0.021332247

ENSG00000088325
TPX2
4.00E−13
0.000751758
−0.147886462

ENSG00000088930
XRN2
1.00E−04
0.054328641
0.120769979

ENSG00000089053
ANAPC5
2.00E−04
0.71210468
−0.020762022

ENSG00000089094
KDM2B
4.00E−08
0.242750733
−0.121485992

ENSG00000089154
GCN1L1
3.00E−09
0.913083626
−0.007259602

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000090061
CCNK
8.00E−08
0.870725186
−0.014115514

ENSG00000090372
STRN4
6.00E−04
0.942223216
0.00735298

ENSG00000090520
DNAJB11
1.00E−04
0.403800964
−0.067101447

ENSG00000090861
AARS
6.00E−04
0.574152586
0.035132718

ENSG00000091127
PUS7
9.00E−04
0.204909104
−0.155033013

ENSG00000091164
TXNL1
1.00E−07
0.371475872
−0.0727392

ENSG00000091317
CMTM6
2.00E−08
0.443439517
0.064753558

ENSG00000092094
OSGEP
2.00E−08
0.977762307
−0.002519015

ENSG00000092853
CLSPN
1.00E−10
0.062944195
0.125340878

ENSG00000092964
DPYSL2
1.72E−06
0.18869348
−0.144294954

ENSG00000093009
CDC45
4.00E−04
0.918341518
0.007977992

ENSG00000093167
LRRFIP2
1.00E−04
0.814819674
−0.032970227

ENSG00000095319
NUP188
5.00E−04
0.409660705
−0.062866839

ENSG00000096401
CDC5L
4.00E−11
0.958393737
−0.003388653

ENSG00000097046
CDC7
3.00E−04
0.543156786
−0.062966344

ENSG00000099331
MYO9B
6.00E−04
0.792985514
0.024635401

ENSG00000099381
SETD1A
1.00E−08
0.334979113
0.098318494

ENSG00000099991
CABIN1
1.00E−08
0.104911155
−0.208959207

ENSG00000100029
PES1
3.00E−04
0.805834098
−0.019606907

ENSG00000100138
NHP2L1
1.00E−04
0.451814068
−0.053140436

ENSG00000100147
CCDC134
6.00E−08
0.397335351
−0.115525081

ENSG00000100242
SUN2
4.00E−04
0.443353969
0.107423956

ENSG00000100258
LMF2
3.01E−04
0.446590324
−0.096455839

ENSG00000100280
AP1B1
1.00E−04
0.155202288
−0.113131916

ENSG00000100296
THOC5
1.00E−04
0.777068501
0.04404948

ENSG00000100345
MYH9
2.10E−13
0.195171025
−0.051020259

ENSG00000100350
FOXRED2
1.00E−04
0.939313293
−0.00792074

ENSG00000100401
RANGAP1
1.00E−04
0.59275986
−0.053239149

ENSG00000100403
ZC3H7B
4.00E−04
0.241293577
−0.127436934

ENSG00000100422
CERK
5.01E−04
0.767879843
−0.038668

ENSG00000100461
RBM23
2.00E−04
0.126115054
−0.188774943

ENSG00000100528
CNIH
2.00E−11
0.396062577
0.115843844

ENSG00000100554
ATP6V1D
1.00E−09
0.428461734
−0.082721884

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000100714
MTHFD1
5.00E−04
0.068239627
0.121426205

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−0.176469607

ENSG00000100813
ACIN1
1.00E−04
0.513552164
−0.041074263

ENSG00000100888
CHD8
5.00E−09
0.833778017
0.019607725

ENSG00000100911
PSME2
6.11E−04
0.954296798
−0.00949908

ENSG00000100994
PYGB
2.02E−04
0.741200463
0.05467102

ENSG00000100997
ABHD12
1.00E−08
0.489735178
−0.117139463

ENSG00000101161
PRPF6
5.00E−04
0.452014829
0.060790849

ENSG00000101182
PSMA7
5.01E−04
0.980181485
0.001199919

ENSG00000101191
DIDO1
9.00E−09
0.846657226
−0.024545447

ENSG00000101224
CDC25B
2.00E−09
0.25893922
0.059946483

ENSG00000101294
HM13
4.00E−04
0.788344267
−0.016820212

ENSG00000101310
SEC23B
2.00E−08
0.242275151
0.116563376

ENSG00000101343
CRNKL1
2.00E−04
0.587849423
0.05818265

ENSG00000101464
PIGU
7.02E−04
0.68308036
−0.052876011

ENSG00000101596
SMCHD1
1.00E−09
0.434566245
−0.059009881

ENSG00000101868
POLA1
2.00E−04
0.520751395
0.053293939

ENSG00000101972
STAG2
7.00E−04
0.001047325
−0.187270211

ENSG00000102054
RBBP7
1.60E−12
0.003411029
−0.129303881

ENSG00000102125
TAZ
7.01E−04
0.35021839
0.152681248

ENSG00000102189
EEA1
8.02E−04
0.70653248
−0.043342085

ENSG00000102245
CD40LG
1.00E−04
0.514830532
0.081808759

ENSG00000102606
ARHGEF7
6.00E−08
0.279523802
−0.128921833

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000102974
CTCF
1.00E−09
0.919312546
−0.009349348

ENSG00000103222
ABCC1
2.00E−04
0.969797812
0.002188323

ENSG00000103415
HMOX2
1.00E−09
0.569411146
0.05835055

ENSG00000103479
RBL2
1.00E−04
0.773913697
−0.038025558

ENSG00000103495
MAZ
1.30E−07
0.642227894
0.032737594

ENSG00000103544
C16orf62
3.01E−04
0.742406188
0.038231542

ENSG00000103591
AAGAB
9.00E−04
0.205123038
0.124804927

ENSG00000104177
MYEF2
7.01E−04
0.774370445
−0.035966517

ENSG00000104365
IKBKB
4.00E−04
0.474002406
0.087889302

ENSG00000104472
CHRAC1
8.00E−04
0.353904047
0.105337178

ENSG00000104517
UBR5
3.00E−10
0.744729033
0.031234126

ENSG00000104518
GSDMD
5.00E−04
0.437398468
−0.076674502

ENSG00000104549
SQLE
1.30E−07
0.043864022
−0.265964104

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000104738
MCM4
1.00E−10
0.915393017
0.003107424

ENSG00000104824
HNRNPL
3.60E−07
0.95648967
0.003621772

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000104852
SNRNP70
9.00E−04
0.594216034
−0.038334929

ENSG00000104886
PLEKHJ1
6.00E−08
0.445334658
0.068851577

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000105221
AKT2
2.00E−04
0.381664023
−0.141483695

ENSG00000105248
CCDC94
3.00E−04
0.324134308
−0.124113502

ENSG00000105281
SLC1A5
2.90E−10
0.106631749
−0.153858078

ENSG00000105329
TGFB1
2.00E−04
0.015301045
−0.221315351

ENSG00000105374
NKG7
9.00E−04
0.272175864
−0.097254231

ENSG00000105401
CDC37
2.02E−04
0.182664767
0.098508161

ENSG00000105486
LIG1
9.00E−04
0.865181674
−0.011170383

ENSG00000105618
PRPF31
4.00E−04
0.189221467
0.102321971

ENSG00000105676
ARMC6
8.00E−04
0.830466125
−0.018392253

ENSG00000105677
TMEM147
5.00E−08
0.824197085
−0.020622451

ENSG00000105810
CDK6
4.00E−08
4.76E−05
−0.145254993

ENSG00000105939
ZC3HAV1
4.00E−04
0.868091195
0.01093142

ENSG00000105953
OGDH
1.20E−08
0.404842964
−0.086222511

ENSG00000106263
EIF3B
1.00E−11
0.448608969
−0.028252846

ENSG00000106268
NUDT1
5.77E−06
0.36073421
0.053967036

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000106443
PHF14
6.00E−04
0.445863703
−0.062088645

ENSG00000106459
NRF1
1.01E−04
0.323046456
−0.119510858

ENSG00000106462
EZH2
3.20E−11
0.08121275
0.130806426

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000106624
AEBP1
1.10E−07
0.158176685
−0.063824438

ENSG00000106628
POLD2
1.00E−08
0.658612976
−0.035385479

ENSG00000106948
AKNA
1.00E−04
0.251174368
−0.100775455

ENSG00000107099
DOCK8
9.00E−10
0.488970714
−0.040530824

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000107223
EDF1
1.00E−09
0.174777133
0.108777319

ENSG00000107672
NSMCE4A
8.00E−04
0.421951683
−0.076069575

ENSG00000107854
TNKS2
1.00E−04
0.358901659
0.113182695

ENSG00000107937
GTPBP4
3.00E−04
0.193844537
0.095836593

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000108094
CUL2
4.00E−08
0.617398064
−0.046747644

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000108256
NUFIP2
5.00E−11
0.429062757
0.11100338

ENSG00000108270
AATF
1.00E−04
0.359806561
−0.064247245

ENSG00000108384
RAD51C
1.00E−09
0.010774857
0.189709393

ENSG00000108424
KPNB1
2.00E−11
8.66E−05
−0.171777065

ENSG00000108439
PNPO
3.00E−08
0.034630355
0.181670952

ENSG00000108479
GALK1
1.00E−04
0.608240213
−0.053110682

ENSG00000108506
INTS2
8.01E−04
0.295086648
0.109973837

ENSG00000108679
LGALS3BP
2.00E−08
0.973226652
0.000565498

ENSG00000108848
LUC7L3
2.60E−07
0.135191506
0.089311012

ENSG00000109062
SLC9A3R1
6.01E−04
0.122301958
−0.064055136

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000109332
UBE2D3
1.00E−08
0.601564183
0.04567695

ENSG00000109445
ZNF330
8.00E−04
0.392762523
−0.09281569

ENSG00000109606
DHX15
2.00E−04
0.687578939
0.016706661

ENSG00000109685
WHSC1
1.00E−11
0.0222009
−0.153361985

ENSG00000109805
NCAPG
9.00E−04
0.002277256
0.259598117

ENSG00000110047
EHD1
9.00E−04
0.373381573
−0.084500637

ENSG00000110075
PPP6R3
4.00E−08
0.652181808
−0.029536425

ENSG00000110108
TMEM109
1.00E−07
0.375160957
−0.055219962

ENSG00000110321
EIF4G2
2.00E−08
0.4789335
−0.030452093

ENSG00000110367
DDX6
6.00E−08
0.469603134
−0.047598358

ENSG00000110497
AMBRA1
5.02E−04
0.151399742
−0.200325064

ENSG00000110619
CARS
2.00E−04
0.186855283
0.157414334

ENSG00000110651
CD81
1.00E−04
0.010480682
−0.130640591

ENSG00000110713
NUP98
1.00E−10
0.656641011
−0.027832725

ENSG00000110955
ATP5B
4.00E−04
0.002969053
0.076326726

ENSG00000111335
OAS2
2.00E−04
0.677929702
0.048737643

ENSG00000111348
ARHGDIB
1.50E−07
0.037505737
−0.051698045

ENSG00000111602
TIMELESS
4.00E−04
0.702100642
0.024415465

ENSG00000111640
GAPDH
6.14E−04
0.68110279
0.024257691

ENSG00000111641
NOP2
1.00E−04
0.785381859
0.025711262

ENSG00000111642
CHD4
1.00E−04
0.289163376
0.048737019

ENSG00000111670
GNPTAB
5.01E−04
0.585766626
0.059976694

ENSG00000111726
CMAS
2.01E−04
0.649986681
0.073406219

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000111906
HDDC2
2.00E−04
0.810276479
−0.022306759

ENSG00000112029
FBXO5
2.00E−08
0.13434145
0.116650476

ENSG00000112159
MDN1
7.00E−08
0.503352158
0.068423753

ENSG00000112200
ZNF451
5.00E−04
0.487557618
0.072986258

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000112576
CCND3
2.00E−04
0.995647363
−0.00039872

ENSG00000112667
DNPH1
3.00E−08
0.220468437
0.223545108

ENSG00000112851
ERBB2IP
3.00E−04
0.005962767
−0.26900197

ENSG00000112972
HMGCS1
1.00E−10
0.049358853
0.122227347

ENSG00000112984
KIF20A
1.00E−08
0.934731349
−0.011172951

ENSG00000113369
ARRDC3
8.03E−04
0.778199879
0.045698203

ENSG00000113522
RAD50
4.00E−08
0.22034331
0.108849135

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000113649
TCERG1
5.00E−04
0.001091576
0.213551854

ENSG00000113810
SMC4
1.00E−11
0.586987805
−0.030468428

ENSG00000114023
FAM162A
1.00E−04
0.569698046
−0.05039296

ENSG00000114030
KPNA1
3.90E−07
0.001820335
−0.311253874

ENSG00000114126
TFDP2
7.00E−09
0.567162468
−0.026000796

ENSG00000114200
BCHE
6.02E−04
0.422143365
0.11979247

ENSG00000114416
FXR1
6.00E−04
0.827823905
0.018508158

ENSG00000114735
HEMK1
1.01E−04
0.020519619
−0.432698852

ENSG00000114737
CISH
2.01E−04
0.710188905
−0.018282662

ENSG00000114867
EIF4G1
4.00E−04
0.49755475
0.028286796

ENSG00000115020
PIKFYVE
7.00E−04
0.874274951
−0.045055571

ENSG00000115053
NCL
5.50E−07
0.060545427
0.042909924

ENSG00000115232
ITGA4
3.00E−09
0.73709161
−0.017356009

ENSG00000115306
SPTBN1
3.00E−14
0.008372115
−0.348514727

ENSG00000115419
GLS
4.00E−04
0.000197719
−0.269875671

ENSG00000115457
IGFBP2
3.00E−04
0.641399806
0.036552753

ENSG00000115464
USP34
1.00E−04
0.352056564
−0.122781815

ENSG00000115524
SF3B1
1.00E−04
0.157426391
0.074199855

ENSG00000115526
CHST10
6.00E−04
0.038600005
−0.351592853

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000115760
BIRC6
1.00E−04
0.297237048
0.088149326

ENSG00000115761
NOL10
9.00E−04
0.442727268
0.090675848

ENSG00000115806
GORASP2
4.00E−08
0.107877983
−0.140430182

ENSG00000115866
DARS
2.00E−08
0.047519868
−0.122885656

ENSG00000116120
FARSB
4.30E−07
0.448807369
0.078225185

ENSG00000116133
DHCR24
7.00E−04
0.242618057
−0.119340931

ENSG00000116213
WRAP73
5.00E−08
0.033620725
−0.365648037

ENSG00000116406
EDEM3
1.00E−04
0.160515088
0.161467793

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000116830
TTF2
1.00E−04
0.605327274
−0.05123716

ENSG00000116863
ADPRHL2
6.00E−04
0.363129878
0.185539492

ENSG00000116984
MTR
3.00E−04
0.692634133
−0.048662075

ENSG00000117318
ID3
4.00E−04
0.306098706
0.13190299

ENSG00000117523
PRRC2C
1.00E−11
0.24687917
0.051514482

ENSG00000117632
STMN1
4.01E−04
0.46870306
0.016853098

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000117724
CENPF
6.00E−04
0.178526649
0.061700857

ENSG00000117906
RCN2
3.00E−08
0.060079639
0.177995705

ENSG00000118007
STAG1
2.04E−04
0.802913841
−0.02813744

ENSG00000118058
MLL
3.50E−07
0.817626816
−0.021608686

ENSG00000118193
KIF14
2.00E−09
0.302902759
0.10403347

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000118513
MYB
2.00E−04
0.964892671
−0.004218901

ENSG00000118816
CCNI
6.90E−07
0.001528498
−0.189161037

ENSG00000119041
GTF3C3
1.00E−04
0.862861391
0.021723507

ENSG00000119397
CNTRL
5.00E−08
0.240770456
−0.130222735

ENSG00000119403
PHF19
2.01E−04
0.072821269
0.168059289

ENSG00000119596
YLPM1
4.00E−09
0.122997252
0.126832643

ENSG00000119638
NEK9
4.00E−04
0.69912267
−0.04034303

ENSG00000119669
IRF2BPL
3.02E−04
0.737023088
−0.046311272

ENSG00000119912
IDE
1.00E−04
0.846898243
−0.022139638

ENSG00000120071
KANSL1
5.00E−09
0.455238668
−0.080812302

ENSG00000120254
MTHFD1L
2.00E−04
0.953621846
0.005118686

ENSG00000120690
ELF1
1.00E−04
0.003793641
−0.220693753

ENSG00000120699
EXOSC8
6.00E−04
0.446432736
0.059033278

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000120738
EGR1
3.01E−04
0.317981925
−0.167567968

ENSG00000120800
UTP20
1.80E−07
0.730921404
0.032446721

ENSG00000120910
PPP3CC
7.00E−04
0.20233537
−0.200494687

ENSG00000121152
NCAPH
1.00E−04
0.569736027
0.064203664

ENSG00000121621
KIF18A
6.01E−04
0.278023728
−0.157166557

ENSG00000121691
CAT
5.00E−04
0.059201981
−0.151859968

ENSG00000121864
ZNF639
5.00E−04
0.468232115
−0.0841423

ENSG00000121892
PDS5A
2.00E−10
0.26251314
−0.063220359

ENSG00000122257
RBBP6
1.25E−09
0.000891329
−0.280964053

ENSG00000122862
SRGN
6.00E−04
0.307943894
−0.179460425

ENSG00000122882
ECD
1.00E−04
0.79331662
0.025252457

ENSG00000122966
CIT
9.00E−04
0.886264235
−0.011615594

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000123144
C19orf43
6.00E−04
0.121848164
0.139094396

ENSG00000123213
NLN
7.02E−04
0.499519365
0.090955024

ENSG00000123338
NCKAP1L
1.20E−11
0.299683199
0.062171215

ENSG00000123473
STIL
8.01E−04
0.246311874
−0.148306759

ENSG00000123485
HJURP
2.00E−08
0.006526616
0.216805783

ENSG00000123983
ACSL3
7.01E−04
0.236015207
0.104976406

ENSG00000124177
CHD6
7.01E−04
0.577660003
−0.071504202

ENSG00000124181
PLCG1
1.00E−04
0.95873485
−0.001417988

ENSG00000124193
SRSF6
3.00E−04
0.119574817
0.116472581

ENSG00000124228
DDX27
5.00E−08
0.834023162
0.015972497

ENSG00000124541
RRP36
2.00E−10
0.604769753
0.044529012

ENSG00000124575
HIST1H1D
1.00E−15
0.457298328
0.015260005

ENSG00000124641
MED20
1.00E−04
0.941332678
−0.01659058

ENSG00000124693
HIST1H3B
2.23E−12
0.254240878
0.040459312

ENSG00000124789
NUP153
3.20E−10
0.677271772
−0.045251116

ENSG00000125304
TM9SF2
7.00E−04
0.431186651
−0.044738316

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000125651
GTF2F1
1.10E−08
0.031215966
−0.168644284

ENSG00000125686
MED1
1.00E−08
0.18711587
−0.124662129

ENSG00000125755
SYMPK
1.00E−09
0.552114085
−0.054422769

ENSG00000125826
RBCK1
1.01E−04
0.817834713
−0.030877268

ENSG00000125885
MCM8
1.20E−07
0.740692289
−0.028115948

ENSG00000125971
DYNLRB1
2.10E−07
0.436287925
−0.07746413

ENSG00000126001
CEP250
7.10E−09
0.148680909
0.141831107

ENSG00000126804
ZBTB1
1.00E−04
0.453845337
−0.079720916

ENSG00000126883
NUP214
1.00E−04
0.847640341
−0.020473757

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000127184
COX7C
3.00E−04
0.392077126
−0.082208185

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−0.012039575

ENSG00000128191
DGCR8
2.00E−08
0.071123809
−0.242947421

ENSG00000128829
EIF2AK4
9.00E−04
0.627581021
−0.077669277

ENSG00000129317
PUS7L
2.00E−04
0.653028133
−0.054700064

ENSG00000129351
ILF3
1.30E−07
0.030039666
−0.082482869

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000130175
PRKCSH
3.00E−08
0.492538567
−0.034477239

ENSG00000130255
RPL36
1.40E−06
0.000331082
−0.237194765

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000130402
ACTN4
3.01E−04
0.05655675
−0.168897398

ENSG00000130640
TUBGCP2
2.00E−04
0.083088036
−0.263652098

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−0.092503983

ENSG00000130816
DNMT1
5.00E−04
0.595705453
−0.027738247

ENSG00000131148
EMC8
5.00E−11
0.89007858
−0.019540666

ENSG00000131174
COX7B
5.00E−04
0.280235251
−0.066677874

ENSG00000131446
MGAT1
5.01E−04
0.513530158
−0.076217655

ENSG00000131467
PSME3
3.01E−04
0.03715923
−0.116973165

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000132142
ACACA
1.00E−04
0.384701339
−0.088267863

ENSG00000132155
RAF1
1.90E−07
0.727868161
0.035824977

ENSG00000132182
NUP210
4.00E−11
0.396376427
−0.053178121

ENSG00000132294
EFR3A
6.00E−04
0.101176956
−0.138753026

ENSG00000132305
IMMT
2.00E−04
0.911802156
−0.008862008

ENSG00000132383
RPA1
1.00E−04
0.536237887
0.027348564

ENSG00000132436
FIGNL1
4.00E−04
0.90689028
0.012761853

ENSG00000132463
GRSF1
3.01E−04
0.003456732
0.144799456

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000132612
VPS4A
3.05E−06
0.187740524
−0.117542241

ENSG00000132646
PCNA
4.00E−09
0.449582299
0.020688405

ENSG00000132680
KIAA0907
7.00E−04
0.406235984
−0.089721055

ENSG00000132842
AP3B1
5.00E−04
0.894277559
0.020029663

ENSG00000132953
XPO4
4.00E−04
0.386914625
−0.098355739

ENSG00000133026
MYH10
1.00E−04
0.734506152
0.038657519

ENSG00000133454
MYO18B
6.00E−11
0.694394285
−0.024618977

ENSG00000133639
BTG1
7.00E−04
0.111632247
−0.307842825

ENSG00000133657
ATP13A3
1.00E−10
0.021301072
−0.237052311

ENSG00000133706
LARS
4.00E−04
0.597497941
−0.035619738

ENSG00000133961
NUMB
9.01E−04
0.646567716
0.059486807

ENSG00000134313
KIDINS220
1.00E−08
0.857549373
0.021963698

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000134480
CCNH
6.00E−04
0.669625945
0.058777209

ENSG00000134516
DOCK2
6.00E−04
0.505754891
0.037062588

ENSG00000134644
PUM1
2.00E−04
0.207254614
−0.119306565

ENSG00000134686
PHC2
8.90E−07
0.974560029
0.001948917

ENSG00000134697
GNL2
2.00E−08
0.31879467
0.080020877

ENSG00000134759
ELP2
2.00E−04
0.297463108
0.107815275

ENSG00000134910
STT3A
2.00E−11
0.248910784
0.068871835

ENSG00000134954
ETS1
5.70E−09
1.27E−05
−0.232324455

ENSG00000134987
WDR36
3.00E−04
0.028738034
0.151716239

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000135316
SYNCRIP
5.00E−08
0.141605449
−0.082838833

ENSG00000135439
AGAP2
6.00E−04
0.408030001
−0.104437193

ENSG00000135521
LTV1
9.00E−04
0.577086029
0.047229663

ENSG00000135679
MDM2
4.90E−07
0.948348125
0.012834459

ENSG00000135763
URB2
4.01E−04
0.668047421
0.04463194

ENSG00000135837
CEP350
1.00E−08
0.152171166
−0.140217831

ENSG00000135905
DOCK10
1.00E−08
0.717332641
0.040604232

ENSG00000135932
CAB39
1.00E−08
0.019948395
−0.200243436

ENSG00000135940
COX5B
4.00E−04
0.629646454
−0.025317297

ENSG00000136051
KIAA1033
2.00E−04
0.30132225
0.128371731

ENSG00000136068
FLNB
2.90E−12
0.062111584
−0.409977879

ENSG00000136104
RNASEH2B
4.20E−07
0.392137768
0.057232924

ENSG00000136146
MED4
8.00E−04
0.169595348
−0.110732537

ENSG00000136167
LCP1
2.00E−04
0.489381124
−0.018010751

ENSG00000136271
DDX56
1.10E−07
0.710493262
−0.028033209

ENSG00000136286
MYO1G
4.00E−08
0.20294865
0.071258537

ENSG00000136381
IREB2
3.00E−04
0.349257048
0.088289702

ENSG00000136492
BRIP1
3.00E−10
0.419920204
−0.069475773

ENSG00000136527
TRA2B
1.00E−04
0.403669503
−0.031939853

ENSG00000136536
MARCH7
1.00E−10
0.683034436
0.035756577

ENSG00000136628
EPRS
1.00E−04
0.75764814
0.018770161

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000136709
WDR33
9.00E−04
0.304508163
−0.081701638

ENSG00000136738
STAM
3.00E−04
0.366470963
0.094693082

ENSG00000136754
ABI1
2.00E−04
0.893753832
−0.015741049

ENSG00000136758
YME1L1
1.00E−04
0.090002669
−0.100978955

ENSG00000136824
SMC2
8.00E−04
0.373245909
0.054833376

ENSG00000136827
TOR1A
1.00E−08
0.306962116
0.113750173

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000136997
MYC
3.00E−08
0.000130485
−0.222358961

ENSG00000137076
TLN1
2.00E−09
0.114582751
−0.09941367

ENSG00000137106
GRHPR
3.00E−04
0.415762699
−0.09172823

ENSG00000137770
CTDSPL2
5.06E−04
0.972005432
−0.008284378

ENSG00000137776
SLTM
2.00E−04
0.100597307
0.119688243

ENSG00000137812
CASC5
9.01E−04
0.164406778
0.150771957

ENSG00000137818
RPLP1
3.04E−04
0.002330818
−0.514464579

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−0.208903322

ENSG00000138081
FBXO11
3.00E−04
0.421443356
−0.098168828

ENSG00000138095
LRPPRC
3.00E−04
0.234050395
−0.065104179

ENSG00000138107
ACTR1A
3.01E−04
0.37194789
−0.072733569

ENSG00000138182
KIF20B
1.00E−10
0.00406547
0.242659079

ENSG00000138231
DBR1
8.00E−04
0.870540124
0.016538189

ENSG00000138442
WDR12
6.00E−08
0.190351341
−0.142989262

ENSG00000138496
PARP9
1.00E−04
0.385276066
0.103537296

ENSG00000138592
USP8
7.06E−04
0.313673018
−0.181127726

ENSG00000138668
HNRNPD
2.40E−07
0.003261874
−0.098862205

ENSG00000138698
RAP1GDS1
5.00E−04
0.715002624
−0.035260421

ENSG00000138778
CENPE
2.00E−10
0.214004921
0.115990377

ENSG00000138795
LEF1
1.00E−09
1.60E−06
−0.210659864

ENSG00000138802
SEC24B
1.00E−09
0.515439824
−0.072741233

ENSG00000139154
AEBP2
2.00E−04
0.48380984
0.088405889

ENSG00000139197
PEX5
9.02E−04
0.510476835
0.078299498

ENSG00000139218
SCAF11
1.00E−08
0.50709776
−0.04074801

ENSG00000139350
NEDD1
1.00E−04
0.725169134
0.037847451

ENSG00000139505
MTMR6
4.00E−08
0.747037745
−0.038766186

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000139620
KANSL2
4.00E−04
0.2859956
0.116502184

ENSG00000139641
ESYT1
6.00E−04
0.115537694
0.094065695

ENSG00000139687
RB1
4.00E−11
0.227456544
0.062123731

ENSG00000139842
CUL4A
8.01E−04
0.735833147
−0.028312464

ENSG00000139946
PELI2
8.01E−04
0.84869402
−0.030488571

ENSG00000140259
MFAP1
4.00E−04
0.286171294
0.110298043

ENSG00000140262
TCF12
2.00E−10
0.025334533
−0.184064816

ENSG00000140299
BNIP2
9.00E−08
0.453644947
0.060595449

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000140525
FANCI
2.00E−04
0.688024573
0.029180218

ENSG00000140829
DHX38
8.00E−08
0.404193545
−0.083781852

ENSG00000140943
MBTPS1
4.00E−04
0.905572549
0.017038735

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000141252
VPS53
2.00E−04
0.91838956
0.011174255

ENSG00000141367
CLTC
2.00E−15
0.808942699
−0.009782716

ENSG00000141378
PTRH2
1.00E−04
0.917590739
−0.014270194

ENSG00000141456
PELP1
2.00E−04
0.806300676
0.019902797

ENSG00000141551
CSNK1D
5.00E−04
0.119201328
−0.129522549

ENSG00000141556
TBCD
1.00E−04
0.591494459
−0.026526545

ENSG00000142002
DPP9
1.00E−04
0.734190324
−0.049637386

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000143106
PSMA5
4.00E−08
0.382567623
0.045346574

ENSG00000143401
ANP32E
1.00E−04
0.915890957
0.004516508

ENSG00000143442
POGZ
2.00E−09
0.037681202
−0.207363006

ENSG00000143476
DTL
3.01E−04
0.748549723
−0.021380096

ENSG00000143514
TP53BP2
7.00E−04
0.283581835
−0.117348193

ENSG00000143624
INTS3
7.01E−04
0.265735445
−0.146742464

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000143924
EML4
7.01E−04
0.028666301
−0.26184158

ENSG00000144028
SNRNP200
8.00E−14
0.023390105
0.101854033

ENSG00000144554
FANCD2
2.00E−04
0.730926111
0.036291397

ENSG00000144559
TAMM41
5.00E−04
0.851527782
0.02836682

ENSG00000144580
RQCD1
2.00E−08
0.506022372
−0.045037202

ENSG00000144895
EIF2A
9.00E−04
0.746023779
−0.024414611

ENSG00000145041
VPRBP
4.00E−04
0.348933992
−0.094987498

ENSG00000145375
SPATA5
1.00E−04
0.784103808
−0.049246739

ENSG00000145604
SKP2
1.00E−04
0.979279396
0.003747348

ENSG00000145675
PIK3R1
4.02E−04
0.168588299
−0.102576778

ENSG00000145741
BTF3
5.00E−04
0.339388798
−0.072822964

ENSG00000145833
DDX46
2.00E−04
0.23392151
0.072701228

ENSG00000146457
WTAP
3.00E−04
0.883760976
0.015398065

ENSG00000146918
NCAPG2
1.50E−07
0.276197103
0.072778556

ENSG00000147130
ZMYM3
2.00E−04
0.059490308
−0.195960662

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000147677
EIF3H
4.01E−04
0.507259945
−0.031197371

ENSG00000148175
STOM
5.00E−04
0.202025121
−0.203176311

ENSG00000148229
POLE3
6.06E−04
0.60752674
−0.042630647

ENSG00000148334
PTGES2
1.04E−04
0.626929001
−0.068481398

ENSG00000148337
CIZ1
3.00E−04
0.65773939
−0.053627564

ENSG00000148396
SEC16A
1.00E−04
0.806810949
0.025438251

ENSG00000148400
NOTCH1
1.00E−04
0.276344103
−0.101708517

ENSG00000148773
MKI67
1.00E−10
0.123777629
0.063404366

ENSG00000148840
PPRC1
5.00E−04
0.85534363
−0.028695475

ENSG00000148843
PDCD11
5.00E−04
0.56753983
−0.05144919

ENSG00000149262
INTS4
4.00E−04
0.697964901
0.097540919

ENSG00000149273
RPS3
2.35E−05
0.448604972
−0.041417003

ENSG00000149308
NPAT
2.00E−04
0.81995279
0.029267153

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000149554
CHEK1
3.00E−08
0.029907425
0.142987957

ENSG00000149806
FAU
3.02E−04
0.009610398
0.1703503

ENSG00000149925
ALDOA
3.02E−04
0.183371478
−0.061277735

ENSG00000150990
DHX37
2.00E−04
0.614661587
−0.044689634

ENSG00000151131
C12orf45
8.00E−04
0.485034329
−0.088403349

ENSG00000151366
NDUFC2
2.00E−09
0.361312276
−0.043896664

ENSG00000151502
VPS26B
2.00E−04
0.277634848
0.100319458

ENSG00000151503
NCAPD3
3.00E−04
0.100416068
0.106975594

ENSG00000151694
ADAM17
7.30E−07
0.446223538
−0.1096626

ENSG00000151702
FLI1
1.00E−04
0.221034285
−0.138078723

ENSG00000151835
SACS
2.00E−04
0.575717819
0.054319675

ENSG00000152082
MZT2B
1.30E−08
0.784207016
−0.02186646

ENSG00000152147
GEMIN6
8.00E−04
0.112633984
0.186427654

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−0.152181062

ENSG00000152818
UTRN
1.00E−04
0.61246869
−0.063349119

ENSG00000153187
HNRNPU
3.00E−04
0.973831029
−0.000601876

ENSG00000153283
CD96
2.00E−04
0.267330877
−0.089143298

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000153922
CHD1
3.00E−09
0.997926928
−0.000811209

ENSG00000154370
TRIM11
3.01E−04
0.010190424
−0.431525912

ENSG00000155097
ATP6V1C1
4.00E−04
0.714750549
−0.035031119

ENSG00000155561
NUP205
1.00E−10
0.810978988
−0.015620768

ENSG00000155827
RNF20
1.00E−08
0.674024322
0.06246891

ENSG00000156273
BACH1
6.00E−04
0.916576258
−0.031050024

ENSG00000156858
PRR14
1.10E−07
0.581714014
−0.069166264

ENSG00000156875
HIAT1
1.00E−04
0.380713082
−0.10910263

ENSG00000156970
BUB1B
4.00E−10
0.947953681
0.006781777

ENSG00000156983
BRPF1
4.00E−04
0.933570558
−0.010817335

ENSG00000157540
DYRK1A
2.00E−09
0.276566574
−0.107710063

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000158290
CUL4B
1.00E−04
0.931575328
−0.009597839

ENSG00000158373
HIST1H2BD
2.00E−08
0.665459706
−0.010325486

ENSG00000158406
HIST1H4H
5.50E−09
0.616647851
0.034929668

ENSG00000158526
TSR2
1.00E−04
0.033164157
0.270897208

ENSG00000158623
COPG2
2.00E−04
0.583240481
−0.080548482

ENSG00000158864
NDUFS2
1.40E−07
0.692802138
0.037508569

ENSG00000158985
CDC42SE2
8.00E−08
0.027991366
−0.145160094

ENSG00000159131
GART
7.00E−04
0.231639477
−0.068059954

ENSG00000159140
SON
1.20E−12
0.122942939
0.067823184

ENSG00000159314
ARHGAP27
2.00E−04
0.839973686
−0.028088528

ENSG00000159720
ATP6V0D1
5.00E−04
0.616798782
0.050867945

ENSG00000160294
MCM3AP
2.00E−04
0.271306147
−0.134887854

ENSG00000160710
ADAR
2.00E−04
0.080829161
−0.088103689

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000160949
TONSL
1.00E−04
0.196335035
−0.17410121

ENSG00000161618
ALDH16A1
2.02E−04
0.73604894
−0.075930576

ENSG00000161980
POLR3K
3.00E−04
0.780264569
0.030710578

ENSG00000162434
JAK1
3.00E−04
0.381361282
−0.087910305

ENSG00000162607
USP1
5.00E−11
0.111472525
−0.094654587

ENSG00000162642
C1orf52
7.06E−04
0.242610098
0.178613459

ENSG00000162664
ZNF326
9.00E−04
0.113292053
0.1523951

ENSG00000163104
SMARCAD1
1.00E−07
0.928265836
−0.008266525

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000163607
GTPBP8
1.00E−04
0.426296869
−0.158064045

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000163808
KIF15
1.00E−04
0.593535319
0.070077932

ENSG00000163902
RPN1
3.00E−04
0.036709758
0.092942803

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000163939
PBRM1
2.00E−04
0.686874801
−0.037496

ENSG00000163946
FAM208A
1.00E−08
0.438939056
−0.067851035

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000164168
TMEM184C
2.50E−08
0.015050183
−0.397412646

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000164209
SLC25A46
2.00E−04
0.530752611
0.054652482

ENSG00000164754
RAD21
1.00E−08
0.756335554
−0.013371036

ENSG00000164978
NUDT2
1.01E−04
0.680662594
−0.053435289

ENSG00000164985
PSIP1
1.00E−04
0.469682012
0.047128687

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000165271
NOL6
2.00E−08
0.335093224
−0.094631942

ENSG00000165304
MELK
2.00E−04
0.351342781
0.077213211

ENSG00000165417
GTF2A1
7.00E−11
0.844760071
−0.015019218

ENSG00000165480
SKA3
2.00E−04
0.96112422
0.004310634

ENSG00000165494
PCF11
2.00E−09
0.168402482
−0.149826279

ENSG00000165502
RPL36AL
5.00E−08
0.586754886
−0.050125431

ENSG00000165527
ARF6
1.00E−10
0.156807609
−0.122434848

ENSG00000165678
GHITM
2.00E−09
0.40434721
−0.044927385

ENSG00000165782
TMEM55B
1.00E−04
0.742872155
0.097568043

ENSG00000165916
PSMC3
2.00E−04
0.327136153
0.067066757

ENSG00000166037
CEP57
1.00E−04
0.563570438
−0.056277887

ENSG00000166226
CCT2
2.00E−04
0.424973179
0.028289737

ENSG00000166747
AP1G1
1.00E−04
0.033859721
−0.180376252

ENSG00000166888
STAT6
1.00E−04
0.047894287
−0.21884119

ENSG00000166963
MAP1A
1.00E−09
0.569547165
0.03924313

ENSG00000166986
MARS
9.00E−08
0.040009981
−0.120193487

ENSG00000167258
CDK12
5.00E−04
0.030045657
−0.185190158

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000167468
GPX4
7.00E−04
0.056273288
0.118694036

ENSG00000167470
MIDN
3.00E−04
0.037975203
−0.404562969

ENSG00000167491
GATAD2A
3.00E−04
0.460886475
−0.052425426

ENSG00000167522
ANKRD11
1.00E−08
0.255387498
0.10026816

ENSG00000167548
MLL2
7.70E−09
0.196266437
−0.106714093

ENSG00000167658
EEF2
8.00E−09
0.147519118
−0.034288496

ENSG00000167670
CHAF1A
1.00E−08
0.388610811
−0.064999638

ENSG00000167747
C19orf48
1.80E−07
0.222151707
−0.136113219

ENSG00000167775
CD320
6.01E−04
0.822695325
0.022736769

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000168159
RNF187
5.00E−04
0.806336099
0.019371782

ENSG00000168264
IRF2BP2
7.60E−07
0.400567441
−0.098542726

ENSG00000168298
HIST1H1E
8.00E−12
0.575494886
0.00693283

ENSG00000168374
ARF4
2.00E−04
0.706405122
−0.070945614

ENSG00000168476
REEP4
8.00E−04
0.228797357
−0.127937767

ENSG00000168575
SLC20A2
4.02E−04
0.354909308
−0.119617959

ENSG00000168906
MAT2A
3.00E−04
0.308184492
−0.065364304

ENSG00000168918
INPP5D
3.00E−04
0.934564983
0.00569134

ENSG00000169018
FEM1B
3.00E−04
0.01910054
−0.397020738

ENSG00000169221
TBC1D10B
8.00E−04
0.845261963
0.037666933

ENSG00000169251
NMD3
3.03E−04
0.950093056
−0.00374493

ENSG00000169375
SIN3A
3.00E−04
0.134711475
−0.125528448

ENSG00000169710
FASN
1.10E−11
0.30709726
−0.046236104

ENSG00000169813
HNRNPF
2.00E−04
0.261636371
−0.045390453

ENSG00000169905
TOR1AIP2
7.00E−04
0.025144824
−0.223803399

ENSG00000169994
MYO7B
3.30E−14
0.067830781
−0.06063889

ENSG00000170004
CHD3
1.00E−08
0.982259628
0.001839786

ENSG00000170242
USP47
2.00E−09
0.545269342
−0.072546866

ENSG00000170430
MGMT
4.00E−04
0.64248843
0.054326376

ENSG00000171202
TMEM126A
8.07E−04
0.731670543
0.060950022

ENSG00000171298
GAA
1.10E−08
0.092998845
−0.248293341

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000171608
PIK3CD
2.00E−08
0.621359547
−0.054808961

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−0.150308959

ENSG00000171861
RNMTL1
8.04E−04
0.07761122
0.249083661

ENSG00000172046
USP19
5.00E−04
0.245610178
−0.156637412

ENSG00000172053
QARS
5.00E−04
0.867300993
0.013028643

ENSG00000172292
CERS6
1.00E−09
0.029552171
−0.205124483

ENSG00000172534
HCFC1
2.87E−12
6.58E−09
−0.313512877

ENSG00000172590
MRPL52
2.10E−06
0.325139446
−0.06780364

ENSG00000172716
SLFN11
2.00E−04
0.664664806
0.04271628

ENSG00000172725
CORO1B
6.00E−04
0.292853887
−0.118190498

ENSG00000172775
FAM192A
1.00E−04
0.366617379
−0.209977577

ENSG00000172795
DCP2
4.00E−04
0.294839777
0.094471533

ENSG00000172893
DHCR7
8.00E−08
0.073439676
−0.22022124

ENSG00000172939
OXSR1
2.01E−04
0.260117099
−0.092965672

ENSG00000172995
ARPP21
7.01E−04
0.648766475
−0.073812799

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000173141
MRP63
1.00E−11
0.385791511
0.081117583

ENSG00000173163
COMMD1
7.00E−04
0.313197556
0.20935172

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000173585
CCR9
4.00E−04
0.004934791
−0.343972085

ENSG00000173598
NUDT4
4.01E−04
0.997345883
−0.001074841

ENSG00000173674
EIF1AX
8.00E−04
0.780846703
0.072635112

ENSG00000173692
PSMD1
2.00E−09
0.749735343
0.022709414

ENSG00000173821
RNF213
1.00E−10
0.78788961
0.011822428

ENSG00000174010
KLHL15
8.01E−04
0.770357983
−0.039693382

ENSG00000174173
TRMT10C
2.00E−04
0.047069196
0.19484858

ENSG00000174197
MGA
2.30E−08
0.926221975
0.009158715

ENSG00000174231
PRPF8
1.00E−10
0.595739886
0.019539188

ENSG00000174238
PITPNA
3.00E−04
0.470422902
−0.066848619

ENSG00000174579
MSL2
5.00E−04
0.027763257
−0.205275001

ENSG00000174851
YIF1A
4.00E−04
0.662843111
0.058226495

ENSG00000175216
CKAP5
1.50E−08
0.03814885
0.117491174

ENSG00000175221
MED16
3.82E−06
0.907545434
−0.022207491

ENSG00000175467
SART1
1.00E−04
0.126941788
−0.10443742

ENSG00000175931
UBE2O
3.00E−04
0.447757287
0.068133312

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000176890
TYMS
4.00E−04
0.016419414
0.072462812

ENSG00000177084
POLE
1.00E−11
0.256661974
0.078668239

ENSG00000177156
TALDO1
8.00E−04
0.975031972
−0.001808282

ENSG00000177370
TIMM22
9.00E−04
0.455177571
0.122153476

ENSG00000177731
FLII
2.00E−04
0.139734019
0.11682969

ENSG00000177733
HNRNPA0
2.00E−04
0.789027425
0.010338975

ENSG00000177885
GRB2
1.00E−08
0.474905024
−0.037372741

ENSG00000178202
KDELC2
5.00E−04
0.480571508
0.092686527

ENSG00000178252
WDR6
1.00E−04
0.9305271
0.005862339

ENSG00000178921
PFAS
5.00E−04
0.196160647
0.110574411

ENSG00000179085
DPM3
4.00E−04
0.434227322
0.195823923

ENSG00000179091
CYC1
6.02E−04
0.55486733
0.052028776

ENSG00000179262
RAD23A
5.10E−07
0.674786887
0.038029829

ENSG00000179409
GEMIN4
7.20E−07
0.143223537
−0.152149612

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

ENSG00000180573
HIST1H2AC
7.04E−04
0.896293947
−0.002455334

ENSG00000181090
EHMT1
9.00E−04
0.697892305
0.047799788

ENSG00000181192
DHTKD1
5.06E−04
0.791904623
−0.080578455

ENSG00000181222
POLR2A
1.00E−12
0.038830003
−0.102840994

ENSG00000181555
SETD2
3.00E−04
0.918631253
0.007282024

ENSG00000181789
COPG1
3.00E−04
0.241621066
0.077715176

ENSG00000182473
EXOC7
6.00E−04
0.343587671
−0.074730044

ENSG00000182481
KPNA2
3.00E−04
0.644150482
−0.032122311

ENSG00000182551
ADI1
9.00E−04
0.372377154
0.072506123

ENSG00000182827
ACBD3
3.00E−08
0.404828614
0.130448872

ENSG00000183495
EP400
6.00E−04
0.637303595
0.055214724

ENSG00000183918
SH2D1A
7.01E−04
0.283846866
0.067991179

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000184357
HIST1H1B
3.00E−14
0.101743718
0.056835835

ENSG00000184432
COPB2
1.00E−04
0.99225242
0.000643147

ENSG00000184445
KNTC1
3.00E−04
0.290700324
0.117936173

ENSG00000184634
MED12
2.00E−09
0.441484568
0.08225596

ENSG00000184661
CDCA2
6.00E−04
0.129977922
−0.116602274

ENSG00000184719
RNLS
9.00E−04
0.124096231
−0.160207128

ENSG00000184825
HIST1H2AH
1.50E−08
0.236178337
0.035788181

ENSG00000184990
SIVA1
5.01E−04
0.001360314
0.174493974

ENSG00000185000
DGAT1
3.01E−04
0.711930638
−0.055676496

ENSG00000185104
FAF1
1.00E−04
0.186505473
−0.111825327

ENSG00000185163
DDX51
4.22E−06
0.69311416
−0.05606435

ENSG00000185236
RAB11B
9.00E−04
0.250648111
−0.08681802

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000185344
ATP6V0A2
2.03E−04
0.449082903
0.078626222

ENSG00000186106
ANKRD46
1.00E−08
0.938464567
0.008636835

ENSG00000186298
PPP1CC
9.02E−04
0.246006029
−0.058739406

ENSG00000186395
KRT10
1.00E−04
0.616095519
0.04261803

ENSG00000186480
INSIG1
3.08E−06
0.573173068
−0.037858571

ENSG00000186517
ARHGAP30
1.00E−04
0.332792401
0.068602551

ENSG00000186566
GPATCH8
9.00E−04
0.836769737
−0.022374401

ENSG00000186575
NF2
5.00E−04
0.511808
0.06843328

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000187257
RSBN1L
2.10E−07
0.682200483
0.045962809

ENSG00000187531
SIRT7
4.01E−04
0.591150723
−0.160016903

ENSG00000187764
SEMA4D
4.00E−04
0.413891066
−0.073148377

ENSG00000187837
HIST1H1C
3.00E−09
0.000257571
0.053651622

ENSG00000188229
TUBB4B
6.00E−08
0.176644347
0.091849122

ENSG00000188486
H2AFX
2.64E−06
0.075491176
0.09777223

ENSG00000188987
HIST1H4D
1.00E−13
0.875362395
0.003774928

ENSG00000196155
PLEKHG4
1.00E−04
0.015595222
−0.295432913

ENSG00000196230
TUBB
2.40E−07
0.534866787
0.035871882

ENSG00000196235
SUPT5H
2.00E−04
0.195564051
−0.152021425

ENSG00000196305
IARS
3.00E−04
0.401865475
0.075934866

ENSG00000196367
TRRAP
3.00E−10
0.181318964
−0.088383498

ENSG00000196396
PTPN1
2.00E−04
0.634603291
0.040420571

ENSG00000196498
NCOR2
6.00E−04
0.072769487
−0.155938346

ENSG00000196504
PRPF40A
1.00E−09
0.142009995
0.08561315

ENSG00000196535
MYO18A
6.00E−04
0.972106963
−0.002927619

ENSG00000196683
TOMM7
3.00E−08
0.90908379
−0.015495382

ENSG00000196700
ZNF512B
2.09E−04
0.699101376
0.063580592

ENSG00000196787
HIST1H2AG
5.50E−08
0.747550904
−0.019583582

ENSG00000196924
FLNA
1.00E−12
0.169192017
−0.078099713

ENSG00000197061
HIST1H4C
1.00E−09
0.897532466
0.002378482

ENSG00000197081
IGF2R
4.10E−09
0.531193218
0.066454289

ENSG00000197102
DYNC1H1
5.00E−10
0.149889643
0.128641432

ENSG00000197153
HIST1H3J
7.00E−11
0.888297027
−0.007272098

ENSG00000197157
SND1
1.01E−04
0.257912014
0.060457678

ENSG00000197312
DDI2
6.01E−04
0.856181146
−0.025215686

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000197409
HIST1H3D
3.00E−12
0.512483364
−0.019287888

ENSG00000197601
FAR1
3.30E−08
0.659187685
−0.041267074

ENSG00000197694
SPTAN1
2.00E−10
0.081327953
−0.18679623

ENSG00000197697
HIST1H2BE
9.00E−08
0.493425798
0.028198489

ENSG00000197746
PSAP
2.00E−10
0.088797396
0.046479701

ENSG00000197903
HIST1H2BK
2.00E−04
0.781823807
−0.022923109

ENSG00000197930
ERO1L
6.50E−07
0.973303548
−0.003430597

ENSG00000198015
MRPL42
2.00E−04
0.883226659
−0.031389992

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000198231
DDX42
6.00E−11
0.824728919
−0.015904689

ENSG00000198276
UCKL1
3.30E−07
0.304042297
−0.145350623

ENSG00000198327
HIST1H4F
3.00E−09
0.208678387
−0.022044471

ENSG00000198339
HIST1H4I
2.00E−08
0.495872312
0.011398728

ENSG00000198374
HIST1H2AL
2.05E−06
0.072591854
0.039969658

ENSG00000198380
GFPT1
2.00E−04
0.636068909
0.045606566

ENSG00000198520
C1orf228
7.80E−07
0.473771444
−0.055437679

ENSG00000198563
DDX39B
8.00E−04
0.271266603
−0.112598519

ENSG00000198604
BAZ1A
5.00E−10
0.704916782
−0.030835374

ENSG00000198646
NCOA6
4.01E−04
0.116549501
−0.173636683

ENSG00000198648
STK39
5.01E−04
0.740902509
0.034721562

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000198730
CTR9
1.00E−09
0.11470634
−0.142355213

ENSG00000198786
MT-ND5
2.00E−08
0.038698438
−0.086785336

ENSG00000198824
CHAMP1
4.00E−04
0.249023725
−0.097569413

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000198917
C9orf114
8.03E−04
0.004093641
0.394051515

ENSG00000198952
SMG5
3.00E−04
0.489633279
0.073022366

ENSG00000203813
HIST1H3H
1.00E−04
0.178969463
−0.025149763

ENSG00000204138
PHACTR4
6.00E−08
0.121133788
−0.222449915

ENSG00000204178
TMEM57
3.00E−04
0.010544799
−0.345157048

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000204256
BRD2
1.00E−08
0.232280315
−0.080114261

ENSG00000204371
EHMT2
1.00E−08
0.297240081
0.090410757

ENSG00000204394
VARS
5.00E−04
0.304208452
−0.069883333

ENSG00000204469
PRRC2A
2.00E−09
0.549464658
0.030387491

ENSG00000204713
TRIM27
8.00E−04
0.790207031
−0.026814299

ENSG00000205268
PDE7A
3.00E−04
0.558620633
−0.048541326

ENSG00000205336
GPR56
8.01E−04
0.228558377
−0.136323001

ENSG00000205629
LCMT1
1.00E−04
0.552673909
−0.089560402

ENSG00000205744
DENND1C
8.04E−04
0.849269508
−0.026567467

ENSG00000213064
SFT2D2
8.00E−04
0.081132453
−0.203416362

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000215301
DDX3X
2.00E−04
0.924710307
−0.00796857

ENSG00000216490
IFI30
4.13E−04
0.518872644
−0.117960608

ENSG00000221829
FANCG
1.00E−04
0.38011695
0.102243151

ENSG00000227057
WDR46
1.00E−10
0.24341875
0.098260531

ENSG00000231925
TAPBP
2.00E−04
0.970644204
−0.003684474

ENSG00000233224
HIST1H2AM
1.00E−11
0.547023548
−0.003832791

ENSG00000234127
TRIM26
9.02E−04
0.038240212
−0.218304118

ENSG00000241978
AKAP2
1.00E−08
0.863267602
0.030178646

ENSG00000253729
PRKDC
1.00E−12
0.427584653
0.050339925

ENSG00000254870
ATP6V1G2-DDX39B
7.01E−04
0.57599435
0.036177813

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000261661
RP11-31I10.4
1.27E−13
NaN
NaN

ENSG00000267740
AC024592.12
4.00E−04
0.536893222
−0.044671372

TABLE 5

Genes that are both TE down and rDiff positive

Gene ID
Gene Name
Translational Efficiency (p-value)
log2(Translational Efficiency)
rDiff (p-value)

ENSG00000137845.9
ADAM10
0.012053048
−0.208903322
8.99999E−10

ENSG00000133657.10
ATP13A3
0.021301072
−0.237052311
9.99999E−11

ENSG00000058668.10
ATP2B4
0.000680955
−0.302809666
9.9999E−10

ENSG00000127152.13
BCL11B
5.40428E−10
−0.517770746
9.999E−09

ENSG00000135932.6
CAB39
0.019948395
−0.200243436
9.999E−09

ENSG00000118816.5
CCNI
0.001528498
−0.189161037
6.89931E−07

ENSG00000173585.11
CCR9
0.004934791
−0.343972085
0.00040005

ENSG00000110651.6
CD81
0.010480682
−0.130640591
0.00010002

ENSG00000158985.9
CDC42SE2
0.027991366
−0.145160094
7.9992E−08

ENSG00000105810.5
CDK6
4.75568E−05
−0.145254993
3.9996E−08

ENSG00000172292.10
CERS6
0.029552171
−0.205124483
9.9999E−10

ENSG00000171310.6
CHST11
0.004536717
−0.14604981
1.19988E−07

ENSG00000131504.11
DIAPH1
0.005406879
−0.213577391
0.0002

ENSG00000120690.9
ELF1
0.003793641
−0.220693753
0.0001

ENSG00000143924.14
EML4
0.028666301
−0.26184158
0.00070056

ENSG00000112851.10
ERBB2IP
0.005962767
−0.26900197
0.00030017

ENSG00000134954.9
ETS1
1.26966E−05
−0.232324455
5.69999E−09

ENSG00000153310.13
FAM49B
0.007506383
−0.139159484
0.0002

ENSG00000169018.5
FEM1B
0.01910054
−0.397020738
0.00030007

ENSG00000033170.12
FUT8
0.006226232
−0.355628717
0.00060004

ENSG00000115419.8
GLS
0.000197719
−0.269875671
0.00040019

ENSG00000078369.10
GNB1
0.011642786
−0.133797709
0.00050004

ENSG00000172534.9
HCFC1
6.57909E−09
−0.313512877
2.87E−12

ENSG00000114735.5
HEMK1
0.020519619
−0.432698852
0.00010083

ENSG00000163349.15
HIPK1
0.020020123
−0.282659771
0.00020003

ENSG00000138668.14
HNRNPD
0.003261874
−0.098862205
2.39976E−07

ENSG00000114030.8
KPNA1
0.001820335
−0.311253874
3.89961E−07

ENSG00000108424.5
KPNB1
8.66259E−05
−0.171777065
2E−11

ENSG00000138795.5
LEF1
1.59715E−06
−0.210659864
9.9999E−10

ENSG00000152601.13
MBNL1
0.00777836
−0.152181062
2E−11

ENSG00000123066.3
MED13L
4.78765E−05
−0.415941737
2.19998E−08

ENSG00000174579.3
MSL2
0.027763257
−0.205275001
0.0005

ENSG00000149480.2
MTA2
2.63948E−05
−0.22354576
5.99994E−09

ENSG00000136997.10
MYC
0.000130485
−0.222358961
2.9997E−08

ENSG00000196155.8
PLEKHG4
0.015595222
−0.295432913
0.00010019

ENSG00000105063.14
PPP6R1
0.029786388
−0.157573098
9.99999E−11

ENSG00000171522.5
PTGER4
0.002288634
−0.274827847
2.39976E−07

ENSG00000184007.11
PTP4A2
0.00039459
−0.142942918
1.49985E−07

ENSG00000122257.14
RBBP6
0.000891329
−0.280964053
1.25E−09

ENSG00000102054.12
RBBP7
0.003411029
−0.129303881
1.6E−12

ENSG00000064490.7
RFXANK
0.015800837
−0.324746409
0.00030015

ENSG00000130255.8
RPL36
0.000331082
−0.237194765
1.39986E−06

ENSG00000137818.7
RPLP1
0.002330818
−0.514464579
0.00030353

ENSG00000100796.13
SMEK1
0.021404696
−0.176469607
1E−11

ENSG00000115306.10
SPTBN1
0.008372115
−0.348514727
3E−14

ENSG00000167978.11
SRRM2
0.027585188
−0.081656945
0.0001

ENSG00000101972.14
STAG2
0.001047325
−0.187270211
0.0007

ENSG00000106290.10
TAF6
0.014175182
−0.210235711
0.00050041

ENSG00000140262.13
TCF12
0.025334533
−0.184064816
2E−10

ENSG00000105329.4
TGFB1
0.015301045
−0.221315351
0.0002

ENSG00000140332.11
TLE3
0.001343794
−0.227829431
1.9998E−08

ENSG00000164168.3
TMEM184C
0.015050183
−0.397412646
2.49998E−08

ENSG00000106609.11
TMEM248
0.005316307
−0.23621242
2.89971E−07

ENSG00000204178.5
TMEM57
0.010544799
−0.345157048
0.00030006

ENSG00000169905.7
TOR1AIP2
0.025144824
−0.223803399
0.00070005

ENSG00000088325.11
TPX2
0.000751758
−0.147886462
4E−13

ENSG00000154370.8
TRIM11
0.010190424
−0.431525912
0.00030064

ENSG00000136878.7
USP20
0.019165529
−0.206602358
1.9998E−08

ENSG00000062650.12
WAPAL
0.019004475
−0.211592796
0.00080001

ENSG00000109685.13
WHSC1
0.0222009
−0.153361985
1E−11

ENSG00000082898.12
XPO1
0.026533538
−0.106116515
1E−11

ENSG00000048405.5
ZNF800
0.020652909
−0.271097499
2.9997E−08

TABLE 6

Motifs and G-quadruplexes in rDiff positive

Gene ID
Gene Name
rDiff (p-value)
Translational Efficiency (p-value)
log2(Translational Efficiency)

Table 6A. rDiff genes with 12-mer motif

ENSG00000088325
TPX2
4.00E−13
0.000751758
−0.147886462

ENSG00000055163
CYFIP2
6.00E−13
0.757974081
−0.02427969

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000181222
POLR2A
1.00E−12
0.038830003
−0.102840994

ENSG00000136068
FLNB
2.90E−12
0.062111584
−0.409977879

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−0.012039575

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−0.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−0.092503983

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−0.152181062

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000086758
HUWE1
2.40E−11
0.464534104
−0.039863394

ENSG00000080345
RIF1
3.00E−11
0.722609171
0.022548991

ENSG00000078674
PCM1
5.00E−11
0.600752059
−0.058335335

ENSG00000131148
EMC8
5.00E−11
0.89007858
−0.019540666

ENSG00000198231
DDX42
6.00E−11
0.824728919
−0.015904689

ENSG00000165417
GTF2A1
7.00E−11
0.844760071
−0.015019218

ENSG00000104738
MCM4
1.00E−10
0.915393017
0.003107424

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000110713
NUP98
1.00E−10
0.656641011
−0.027832725

ENSG00000148773
MKI67
1.00E−10
0.123777629
0.063404366

ENSG00000055483
USP36
2.00E−10
0.857880476
0.014047197

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000197694
SPTAN1
2.00E−10
0.081327953
−0.18679623

ENSG00000087460
GNAS
3.00E−10
0.461136397
−0.032870857

ENSG00000104517
UBR5
3.00E−10
0.744729033
0.031234126

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−0.150308959

ENSG00000124789
NUP153
3.20E−10
0.677271772
−0.045251116

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−0.208903322

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−0.205302853

ENSG00000084093
REST
1.00E−09
0.221405653
−0.118069779

ENSG00000101596
SMCHD1
1.00E−09
0.434566245
−0.059009881

ENSG00000125755
SYMPK
1.00E−09
0.552114085
−0.054422769

ENSG00000138795
LEF1
1.00E−09
1.60E−06
−0.210659864

ENSG00000172292
CERS6
1.00E−09
0.029552171
−0.205124483

ENSG00000198730
CTR9
1.00E−09
0.11470634
−0.142355213

ENSG00000013810
TACC3
2.00E−09
0.886452126
−0.009226853

ENSG00000101224
CDC25B
2.00E−09
0.25893922
0.059946483

ENSG00000137076
TLN1
2.00E−09
0.114582751
−0.09941367

ENSG00000143442
POGZ
2.00E−09
0.037681202
−0.207363006

ENSG00000157540
DYRK1A
2.00E−09
0.276566574
−0.107710063

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000165494
PCF11
2.00E−09
0.168402482
−0.149826279

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000132646
PCNA
4.00E−09
0.449582299
0.020688405

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000197081
IGF2R
4.10E−09
0.531193218
0.066454289

ENSG00000134954
ETS1
5.70E−09
1.27E−05
−0.232324455

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000114126
TFDP2
7.00E−09
0.567162468
−0.026000796

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000054654
SYNE2
9.00E−09
0.143319349
−0.17547751

ENSG00000101191
DIDO1
9.00E−09
0.846657226
−0.024545447

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000099381
SETD1A
1.00E−08
0.334979113
0.098318494

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000125686
MED1
1.00E−08
0.18711587
−0.124662129

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000135905
DOCK10
1.00E−08
0.717332641
0.040604232

ENSG00000135932
CAB39
1.00E−08
0.019948395
−0.200243436

ENSG00000139218
SCAF11
1.00E−08
0.50709776
−0.04074801

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000167522
ANKRD11
1.00E−08
0.255387498
0.10026816

ENSG00000167670
CHAF1A
1.00E−08
0.388610811
−0.064999638

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000125651
GTF2F1
1.10E−08
0.031215966
−0.168644284

ENSG00000171298
GAA
1.10E−08
0.092998845
−0.248293341

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000110321
EIF4G2
2.00E−08
0.4789335
−0.030452093

ENSG00000128191
DGCR8
2.00E−08
0.071123809
−0.242947421

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000144580
RQCD1
2.00E−08
0.506022372
−0.045037202

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000113522
RAD50
4.00E−08
0.22034331
0.108849135

ENSG00000115806
GORASP2
4.00E−08
0.107877983
−0.140430182

ENSG00000104886
PLEKHJ1
6.00E−08
0.445334658
0.068851577

ENSG00000110367
DDX6
6.00E−08
0.469603134
−0.047598358

ENSG00000084733
RAB10
7.00E−08
0.078220422
−0.136343032

ENSG00000140829
DHX38
8.00E−08
0.404193545
−0.083781852

ENSG00000158985
CDC42SE2
8.00E−08
0.027991366
−0.145160094

ENSG00000070756
PABPC1
1.00E−07
0.067231582
−0.133311245

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000103495
MAZ
1.30E−07
0.642227894
0.032737594

ENSG00000080815
PSEN1
1.50E−07
0.468385762
−0.105188191

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000002822
MAD1L1
1.70E−07
0.758278428
−0.03032717

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000138668
HNRNPD
2.40E−07
0.003261874
−0.098862205

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000136104
RNASEH2B
4.20E−07
0.392137768
0.057232924

ENSG00000135679
MDM2
4.90E−07
0.948348125
0.012834459

ENSG00000179262
RAD23A
5.10E−07
0.674786887
0.038029829

ENSG00000071626
DAZAP1
5.20E−07
0.060128417
−0.110195121

ENSG00000197930
ERO1L
6.50E−07
0.973303548
−0.003430597

ENSG00000118816
CCNI
6.90E−07
0.001528498
−0.189161037

ENSG00000179409
GEMIN4
7.20E−07
0.143223537
−0.152149612

ENSG00000074603
DPP8
1.09E−06
0.371935225
−0.109929668

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000064419
TNPO3
1.00E−04
0.030219393
−0.182349237

ENSG00000068796
KIF2A
1.00E−04
0.056041279
0.123499472

ENSG00000077097
TOP2B
1.00E−04
0.84957972
0.01045839

ENSG00000100401
RANGAP1
1.00E−04
0.59275986
−0.053239149

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000107854
TNKS2
1.00E−04
0.358901659
0.113182695

ENSG00000110651
CD81
1.00E−04
0.010480682
−0.130640591

ENSG00000111642
CHD4
1.00E−04
0.289163376
0.048737019

ENSG00000124181
PLCG1
1.00E−04
0.95873485
−0.001417988

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000138496
PARP9
1.00E−04
0.385276066
0.103537296

ENSG00000139350
NEDD1
1.00E−04
0.725169134
0.037847451

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000141556
TBCD
1.00E−04
0.591494459
−0.026526545

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000151702
FLI1
1.00E−04
0.221034285
−0.138078723

ENSG00000156875
HIAT1
1.00E−04
0.380713082
−0.10910263

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000166747
AP1G1
1.00E−04
0.033859721
−0.180376252

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000205629
LCMT1
1.00E−04
0.552673909
−0.089560402

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000148334
PTGES2
1.04E−04
0.626929001
−0.068481398

ENSG00000055130
CUL1
2.00E−04
0.24134893
−0.116033963

ENSG00000077232
DNAJC10
2.00E−04
0.043053807
−0.322931196

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000103222
ABCC1
2.00E−04
0.969797812
0.002188323

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000110619
CARS
2.00E−04
0.186855283
0.157414334

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000140525
FANCI
2.00E−04
0.688024573
0.029180218

ENSG00000144554
FANCD2
2.00E−04
0.730926111
0.036291397

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000151502
VPS26B
2.00E−04
0.277634848
0.100319458

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000177731
FLII
2.00E−04
0.139734019
0.11682969

ENSG00000196396
PTPN1
2.00E−04
0.634603291
0.040420571

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000072778
ACADVL
2.01E−04
0.634381953
0.052306846

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000185344
ATP6V0A2
2.03E−04
0.449082903
0.078626222

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000011295
TTC19
3.00E−04
0.726452954
0.048391976

ENSG00000036257
CUL3
3.00E−04
0.568119382
0.048886832

ENSG00000064115
TM7SF3
3.00E−04
0.921247137
0.007233323

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000167470
MIDN
3.00E−04
0.037975203
−0.404562969

ENSG00000167491
GATAD2A
3.00E−04
0.460886475
−0.052425426

ENSG00000169018
FEM1B
3.00E−04
0.01910054
−0.397020738

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000174238
PITPNA
3.00E−04
0.470422902
−0.066848619

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMG5
3.00E−04
0.489633279
0.073022366

ENSG00000205268
PDE7A
3.00E−04
0.558620633
−0.048541326

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000120738
EGR1
3.01E−04
0.317981925
−0.167567968

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000130402
ACTN4
3.01E−04
0.05655675
−0.168897398

ENSG00000073060
SCARB1
4.00E−04
0.444106259
−0.124760329

ENSG00000100242
SUN2
4.00E−04
0.443353969
0.107423956

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000119638
NEK9
4.00E−04
0.69912267
−0.04034303

ENSG00000140943
MBTPS1
4.00E−04
0.905572549
0.017038735

ENSG00000156983
BRPF1
4.00E−04
0.933570558
−0.010817335

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000072364
AFF4
4.01E−04
0.18444246
−0.147821651

ENSG00000198646
NCOA6
4.01E−04
0.116549501
−0.173636683

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000112200
ZNF451
5.00E−04
0.487557618
0.072986258

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000130816
DNMT1
5.00E−04
0.595705453
−0.027738247

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000100422
CERK
5.01E−04
0.767879843
−0.038668

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000033170
FUT8
6.00E−04
0.006226232
−0.355628717

ENSG00000063245
EPN1
6.00E−04
0.095672127
−0.260058118

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000115526
CHST10
6.00E−04
0.038600005
−0.351592853

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000184661
CDCA2
6.00E−04
0.129977922
−0.116602274

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000115020
PIKFYVE
7.00E−04
0.874274951
−0.045055571

ENSG00000120910
PPP3CC
7.00E−04
0.20233537
−0.200494687

ENSG00000133639
BTG1
7.00E−04
0.111632247
−0.307842825

ENSG00000143514
TP53BP2
7.00E−04
0.283581835
−0.117348193

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000169905
TOR1AIP2
7.00E−04
0.025144824
−0.223803399

ENSG00000102125
TAZ
7.01E−04
0.35021839
0.152681248

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000123983
ACSL3
7.01E−04
0.236015207
0.104976406

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000083312
TNPO1
8.00E−04
0.96323084
0.002633087

ENSG00000104472
CHRAC1
8.00E−04
0.353904047
0.105337178

ENSG00000105676
ARMC6
8.00E−04
0.830466125
−0.018392253

ENSG00000136824
SMC2
8.00E−04
0.373245909
0.054833376

ENSG00000168476
REEP4
8.00E−04
0.228797357
−0.127937767

ENSG00000173674
EIF1AX
8.00E−04
0.780846703
0.072635112

ENSG00000104852
SNRNP70
9.00E−04
0.594216034
−0.038334929

ENSG00000105486
LIG1
9.00E−04
0.865181674
−0.011170383

ENSG00000135521
LTV1
9.00E−04
0.577086029
0.047229663

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

ENSG00000185236
RAB11B
9.00E−04
0.250648111
−0.08681802

ENSG00000133961
NUMB
9.01E−04
0.646567716
0.059486807

Table 6B. rDiff genes with 9-mer motif

ENSG00000088325
TPX2
4.00E−13
0.000751758
−0.147886462

ENSG00000055163
CYFIP2
6.00E−13
0.757974081
−0.02427969

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000181222
POLR2A
1.00E−12
0.038830003
−0.102840994

ENSG00000136068
FLNB
2.90E−12
0.062111584
−0.409977879

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−0.012039575

ENSG00000055044
NOP58
1.00E−11
0.905915474
−0.006508419

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−0.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−0.092503983

ENSG00000108424
KPNB1
2.00E−11
8.66E−05
−0.171777065

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−0.152181062

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000086758
HUWE1
2.40E−11
0.464534104
−0.039863394

ENSG00000080345
RIF1
3.00E−11
0.722609171
0.022548991

ENSG00000139687
RB1
4.00E−11
0.227456544
0.062123731

ENSG00000078674
PCM1
5.00E−11
0.600752059
−0.058335335

ENSG00000131148
EMC8
5.00E−11
0.89007858
−0.019540666

ENSG00000162607
USP1
5.00E−11
0.111472525
−0.094654587

ENSG00000198231
DDX42
6.00E−11
0.824728919
−0.015904689

ENSG00000165417
GTF2A1
7.00E−11
0.844760071
−0.015019218

ENSG00000087087
SRRT
1.00E−10
0.966692349
0.001824104

ENSG00000104738
MCM4
1.00E−10
0.915393017
0.003107424

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000110713
NUP98
1.00E−10
0.656641011
−0.027832725

ENSG00000148773
MKI67
1.00E−10
0.123777629
0.063404366

ENSG00000174231
PRPF8
1.00E−10
0.595739886
0.019539188

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000140262
TCF12
2.00E−10
0.025334533
−0.184064816

ENSG00000197694
SPTAN1
2.00E−10
0.081327953
−0.18679623

ENSG00000087460
GNAS
3.00E−10
0.461136397
−0.032870857

ENSG00000104517
UBR5
3.00E−10
0.744729033
0.031234126

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−0.150308959

ENSG00000124789
NUP153
3.20E−10
0.677271772
−0.045251116

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−0.208903322

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−0.205302853

ENSG00000084093
REST
1.00E−09
0.221405653
−0.118069779

ENSG00000100554
ATP6V1D
1.00E−09
0.428461734
−0.082721884

ENSG00000101596
SMCHD1
1.00E−09
0.434566245
−0.059009881

ENSG00000125755
SYMPK
1.00E−09
0.552114085
−0.054422769

ENSG00000138795
LEF1
1.00E−09
1.60E−06
−0.210659864

ENSG00000172292
CERS6
1.00E−09
0.029552171
−0.205124483

ENSG00000198730
CTR9
1.00E−09
0.11470634
−0.142355213

ENSG00000013810
TACC3
2.00E−09
0.886452126
−0.009226853

ENSG00000066279
ASPM
2.00E−09
0.013635649
0.181712013

ENSG00000118193
KIF14
2.00E−09
0.302902759
0.10403347

ENSG00000137076
TLN1
2.00E−09
0.114582751
−0.09941367

ENSG00000143442
POGZ
2.00E−09
0.037681202
−0.207363006

ENSG00000151366
NDUFC2
2.00E−09
0.361312276
−0.043896664

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000165494
PCF11
2.00E−09
0.168402482
−0.149826279

ENSG00000204469
PRRC2A
2.00E−09
0.549464658
0.030387491

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000132646
PCNA
4.00E−09
0.449582299
0.020688405

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000197081
IGF2R
4.10E−09
0.531193218
0.066454289

ENSG00000134954
ETS1
5.70E−09
1.27E−05
−0.232324455

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000114126
TFDP2
7.00E−09
0.567162468
−0.026000796

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000054654
SYNE2
9.00E−09
0.143319349
−0.17547751

ENSG00000101191
DIDO1
9.00E−09
0.846657226
−0.024545447

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000099381
SETD1A
1.00E−08
0.334979113
0.098318494

ENSG00000099991
CABIN1
1.00E−08
0.104911155
−0.208959207

ENSG00000109332
UBE2D3
1.00E−08
0.601564183
0.04567695

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000125686
MED1
1.00E−08
0.18711587
−0.124662129

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000134313
KIDINS220
1.00E−08
0.857549373
0.021963698

ENSG00000135905
DOCK10
1.00E−08
0.717332641
0.040604232

ENSG00000135932
CAB39
1.00E−08
0.019948395
−0.200243436

ENSG00000139218
SCAF11
1.00E−08
0.50709776
−0.04074801

ENSG00000155827
RNF20
1.00E−08
0.674024322
0.06246891

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000167522
ANKRD11
1.00E−08
0.255387498
0.10026816

ENSG00000167670
CHAF1A
1.00E−08
0.388610811
−0.064999638

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000125651
GTF2F1
1.10E−08
0.031215966
−0.168644284

ENSG00000171298
GAA
1.10E−08
0.092998845
−0.248293341

ENSG00000175216
CKAP5
1.50E−08
0.03814885
0.117491174

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000084774
CAD
2.00E−08
0.242515439
0.087577807

ENSG00000110321
EIF4G2
2.00E−08
0.4789335
−0.030452093

ENSG00000128191
DGCR8
2.00E−08
0.071123809
−0.242947421

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000144580
RQCD1
2.00E−08
0.506022372
−0.045037202

ENSG00000171608
PIK3CD
2.00E−08
0.621359547
−0.054808961

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000164168
TMEM184C
2.50E−08
0.015050183
−0.397412646

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000108439
PNPO
3.00E−08
0.034630355
0.181670952

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000117906
RCN2
3.00E−08
0.060079639
0.177995705

ENSG00000130175
PRKCSH
3.00E−08
0.492538567
−0.034477239

ENSG00000136997
MYC
3.00E−08
0.000130485
−0.222358961

ENSG00000113522
RAD50
4.00E−08
0.22034331
0.108849135

ENSG00000115806
GORASP2
4.00E−08
0.107877983
−0.140430182

ENSG00000105677
TMEM147
5.00E−08
0.824197085
−0.020622451

ENSG00000135316
SYNCRIP
5.00E−08
0.141605449
−0.082838833

ENSG00000104886
PLEKHJ1
6.00E−08
0.445334658
0.068851577

ENSG00000110367
DDX6
6.00E−08
0.469603134
−0.047598358

ENSG00000188229
TUBB4B
6.00E−0S
0.176644347
0.091849122

ENSG00000084733
RAB10
7.00E−08
0.078220422
−0.136343032

ENSG00000140829
DHX38
S.00E−08
0.404193545
−0.083781852

ENSG00000158985
CDC42SE2
8.00E−08
0.027991366
−0.145160094

ENSG00000166986
MARS
9.00E−08
0.040009981
−0.120193487

ENSG00000070756
PA8PC1
1.00E−07
0.067231582
−0.13331124S

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000103495
MAZ
1.30E−07
0.642227894
0.032737594

ENSG00000080815
PSEN1
1.50E−07
0.468385762
−0.105188191

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000002822
MAD1L1
1.70E−07
0.758278428
−0.03032717

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000120800
UTP20
1.80E−07
0.730921404
0.032446721

ENSG00000167747
C19orf48
1.80E−07
0.222151707
−0.136113219

ENSG00000132155
RAF1
1.90E−07
0.727868161
0.035824977

ENSG00000138668
HNRNPD
2.40E−07
0.003261874
−0.098862205

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000196230
TUBB
2.40E−07
0.534866787
0.035871882

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000198276
UCKL1
3.30E−07
0.304042297
−0.145350623

ENSG00000136104
RNASEH2B
4.20E−07
0.392137768
0.057232924

ENSG00000135679
MDM2
4.90E−07
0.948348125
0.012834459

ENSG00000179262
RAD23A
5.10E−07
0.674786887
0.038029829

ENSG00000071626
DAZAP1
5.20E−07
0.060128417
−0.110195121

ENSG00000115053
NCL
5.50E−07
0.060545427
0.042909924

ENSG00000197930
ERO1L
6.50E−07
0.973303548
−0.003430597

ENSG00000118816
CCNI
6.90E−07
0.001528498
−0.189161037

ENSG00300179409
GEMIN4
7.20E−07
0.143223537
−0.152149612

ENSG00000151694
ADAM17
7.30E−07
0.446223538
−0.1096626

ENSG00000074603
DPP8
1.09E−06
0.371935225
−0.109929668

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000132612
VPS4A
3.05E−06
0.187740524
−0.117542241

ENSG00000186480
INSIG1
3.08E−06
0.573173068
−0.037858571

ENSG00000149273
RPS3
2.35E−05
0.448604972
−0.041417003

ENSG00000038219
BOD1L1
1.00E−04
0.003376816
0.278967432

ENSG00000051523
CYBA
1.00E−04
0.816434248
0.0204381

ENSG00000068796
KIF2A
1.00E−04
0.056041279
0.123499472

ENSG00000072310
SREBF1
1.00E−04
0.744899078
−0.026352209

ENSG00000077097
TOP2B
1.00E−04
0.84957972
0.01045839

ENSG00000100401
RANGAP1
1.00E−04
0.59275986
−0.053239149

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000107854
TNKS2
1.00E−04
0.358901659
0.113182695

ENSG00000110651
CD81
1.00E−04
0.010480682
−0.130640591

ENSG00000111642
CHD4
1.00E−04
0.289163376
0.048737019

ENSG00000119041
GTF3C3
1.00E−04
0.862861391
0.021723507

ENSG00000124181
PLCG1
1.00E−04
0.95873485
−0.001417988

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000136758
YME1L1
1.00E−04
0.090002669
−0.100978955

ENSG00000139350
NEDD1
1.00E−04
0.725169134
0.037847451

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000141556
TBCD
1.00E−04
0.591494459
−0.026526545

ENSG00000142002
DPP9
1.00E−04
0.734190324
−0.049637386

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000156875
HIAT1
1.00E−04
0.380713082
−0.10910263

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000172775
FAM192A
1.00E−04
0.366617379
−0.209977577

ENSG00000178252
WDR6
1.00E−04
0.9305271
0.005862339

ENSG00000184432
COPB2
1.00E−04
0.99225242
0.000643147

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000205629
LCMT1
1.00E−04
0.552673909
−0.089560402

ENSG00000221829
FANCG
1.00E−04
0.38011695
0.102243151

ENSG00000038210
PI4K2B
1.01E−04
0.689067203
0.060060784

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000106459
NRF1
1.01E−04
0.323046456
−0.119510858

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000148334
PTGES2
1.04E−04
0.626929001
−0.068481398

ENSG00000055130
CUL1
2.00E−04
0.24134893
−0.116033963

ENSG00000077232
DNAJC10
2.00E−04
0.043053807
−0.322931196

ENSG00000088247
KHSRP
2.00E−04
0.673716802
−0.021332247

ENSG00000089053
ANAPC5
2.00E−04
0.71210468
−0.020762022

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000103222
ABCC1
2.00E−04
0.969797812
0.002188323

ENSG00000105221
AKT2
2.00E−04
0.381664023
−0.141483695

ENSG00000105329
TGFB1
2.00E−04
0.015301045
−0.221315351

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000111906
HDDC2
2.00E−04
0.810276479
−0.022306759

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000144554
FANCD2
2.00E−04
0.730926111
0.036291397

ENSG00000145833
DDX46
2.00E−04
0.23392151
0.072701228

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000151502
VPS26B
2.00E−04
0.277634848
0.100319458

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000144431
FLII
2.00E−04
0.139734019
0.11682969

ENSG00000196396
PTPN1
2.00E−04
0.634603291
0.040420571

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000111726
CMAS
2.01E−04
0.649986681
0.073406219

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000119403
PHF19
2.01E−04
0.072821269
0.168059289

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000100994
PTGB
2.02E−04
0.741200463
0.05467102

ENSG00000105401
CDC37
2.02E−04
0.182664767
0.098508161

ENSG00000185344
ATP6V0A2
2.03E−04
0.449082903
0.078626222

ENSG00000118007
STAG1
2.04E−04
0.802913741
−0.02813744

ENSG00000196700
ZNF512B
2.09E−04
0.699101376
0.063580592

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000011295
TTC19
3.00E−04
0.726452954
0.048391976

ENSG00000036257
CUL3
3.00E−04
0.568119382
0.048886832

ENSG00000064115
TM7SF3
3.00E−04
0.921247137
0.007233323

ENSG00000064490
RFXANK
3.00E−04
0.015800837
−0.324746409

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000124193
SRSF6
3.00E−04
0.119574817
0.116472581

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000137106
GRHPR
3.00E−04
0.415762699
−0.09172823

ENSG00000138081
FBXO11
3.00E−04
0.421443356
−0.098168828

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000167470
MIDN
3.00E−04
0.037975203
−0.404562969

ENSG00000167491
GATAD2A
3.00E−04
0.460886475
−0.052425426

ENSG00000169018
FEM1B
3.00E−04
0.01910054
−0.397020738

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000174238
PITPNA
3.00E−04
0.470422902
−0.066848619

ENSG00000175931
UBE2O
3.00E−04
0.447757287
0.068133312

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMG5
3.00E−04
0.489633279
0.073022366

ENSG00000205268
PDE7A
3.00E−04
0.558620633
−0.048541326

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000120738
EGR1
3.01E−04
0.317981925
−0.167567968

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000130402
ACTN4
3.01E−04
0.05655675
−0.168897398

ENSG00000131467
PSME3
3.01E−04
0.03715923
−0.116973165

ENSG00000154370
TRIM11
3.01E−04
0.010190424
−0.431525912

ENSG00000073060
SCARB1
4.00E−04
0.44106259
−0.124760329

ENSG00000093009
CDC45
4.00E−04
0.918341518
0.007977992

ENSG00000100242
SUN2
4.00E−04
0.443353969
0.107423956

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000104365
IKBKB
4.00E−04
0.474002406
0.087889302

ENSG00000105939
ZC3HAV1
4.00E−04
0.868091195
0.01093142

ENSG00000114867
EIF4G1
4.00E−04
0.49755475
0.028286796

ENSG00000115419
GLS
4.00E−04
0.000197719
−0.269875671

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000119638
NEK9
4.00E−04
0.69912267
−0.04034303

ENSG00000140943
MBTPS1
4.00E−04
0.905572549
0.017038735

ENSG00000156983
BRPF1
4.00E−04
0.933570558
−0.010817335

ENSG00000172795
DCP2
4.00E−04
0.294839777
0.094471533

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000072364
AFF4
4.01E−04
0.18444246
−0.147821651

ENSG00000135763
URB2
4.01E−04
0.668047421
0.04463194

ENSG00000198646
NCOA6
4.01E−04
0.116549501
−0.173636683

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000216490
IFI30
4.13E−04
0.518872644
−0.117960608

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000112200
ZNF451
5.00E−04
0.487557618
0.072986258

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000130816
DNMT1
5.00E−04
0.595705453
−0.027738247

ENSG00000132842
AP3B1
5.00E−04
0.894277559
0.020029663

ENSG00000138698
RAP1GDS1
5.00E−04
0.715002624
−0.035260421

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000174579
MSL2
5.00E−04
0.027763257
−0.205275001

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000186575
NF2
5.00E−04
0.511808
0.06843328

ENSG00000100422
CERK
5.01E−04
0.767879843
−0.038668

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000033170
FUT8
6.00E−04
0.006226232
−0.355628717

ENSG00000060491
OGFR
6.00E−04
0.881572577
−0.018437371

ENSG00000063245
EPN1
6.00E−04
0.095672127
−0.260058118

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000090372
STRN4
6.00E−04
0.942223216
0.00735298

ENSG00000115526
CHST10
6.00E−04
0.038600005
−0.351592853

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000109062
SLC9A3R1
6.01E−04
0.122301958
−0.064055136

ENSG00000167775
CD320
6.01E−04
0.822695325
0.022736769

ENSG00000197312
DDI2
6.01E−04
0.856181146
−0.025215686

ENSG00000011376
LARS2
6.02E−04
0.269847002
−0.142543886

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000115020
PIKFYVE
7.00E−04
0.874274951
−0.045055571

ENSG00000116133
DHCR24
7.00E−04
0.242618057
−0.119340931

ENSG00000120910
PPP3CC
7.00E−04
0.20233537
−0.200494687

ENSG00000133639
BTG1
7.00E−04
0.111632247
−0.307842825

ENSG00000143514
TP53BP2
7.00E−04
0.283581835
−0.117348193

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000169905
TOR1AIP2
7.00E−04
0.025144824
−0.223803399

ENSG00000021762
OSBPL5
7.01E−04
0.905417327
−0.030769757

ENSG00000102125
TAZ
7.01E−04
0.35021839
0.152681248

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000123983
ACSL3
7.01E−04
0.236015207
0.104976406

ENSG00000123213
NLN
7.02E−04
0.499519365
0.090955024

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000082212
ME2
8.00E−04
0.795777072
−0.028699073

ENSG00000083312
TNPO1
8.00E−04
0.96323084
0.002633087

ENSG00000104472
CHRAC1
8.00E−04
0.353904047
0.105337178

ENSG00000105676
ARMC6
8.00E−04
0.830466125
−0.018392253

ENSG00000138231
DBR1
8.00E−04
0.870540124
0.016538189

ENSG00000168476
REEP4
8.00E−04
0.228797357
−0.127937767

ENSG00000169221
TBC1D10B
8.00E−04
0.845261963
0.037666933

ENSG00000173674
EIF1AX
8.00E−04
0.780846703
0.072635112

ENSG00000177156
TALDO1
8.00E−04
0.975031972
−0.001808282

ENSG00000204713
TR1M27
8.00E−04
0.790207031
−0.026814299

ENSG00000139946
PELI2
8.01E−04
0.84869402
−0.030488571

ENSG00000174010
KLHL15
8.01E−04
0.770357983
−0.039693382

ENSG00000171861
RNMTL1
8.04E−04
0.07761122
0.249083661

ENSG00000171202
TMEM126A
8.07E−04
0.731670543
0.060950022

ENSG00000081791
KIAA0141
9.00E−04
0.905406058
−0.017374448

ENSG00000104852
SNRNP70
9.00E−04
0.594216034
−0.038334929

ENSG00000105486
LIG1
9.00E−04
0.865181674
−0.011170383

ENSG00000115761
NOL10
9.00E−04
0.442727268
0.090675848

ENSG00000136709
WDR33
9.00E−04
0.304508163
−0.081701638

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

ENSG00000184719
RNLS
9.00E−04
0.124096231
−0.160207128

ENSG00000185236
RAB11B
9.00E−04
0.250648111
−0.08681802

ENSG00000133961
NUMB
9.01E−04
0.646567716
0.059486807

Table 6C. rDiff genes with G-Quadruplex structure

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−.012039575

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−.092503983

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−.152181062

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000198231
DDX42
6.00E−11
0.824728919
−.015904689

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000104517
UBR5
3.00E−10
0.744729033
0.031234126

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−0.150308959

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−0.208903322

ENSG00000058668
ATP2B4
1.00E−09
0.000680955
−0.302809666

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−0.205302853

ENSG00000125755
SYMPK
1.00E−09
0.552114085
−0.054422769

ENSG00000172292
CERS6
1.00E−09
0.029552171
−0.205124483

ENSG00000013810
TACC3
2.00E−09
0.886452126
−0.009226853

ENSG00000066279
ASPM
2.00E−09
0.013635649
0.181712013

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000106628
POLD2
1.00E−08
0.658612976
−0.035385479

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000064613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000093094
OSGEP
2.00E−08
0.977762307
−0.002519015

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000171608
PIK3CD
2.00E−08
0.621359547
−0.054808961

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000116698
SMG7
6.00E−08
0.886915303
−0.013938554

ENSG00000102606
ARHGEF7
6.00E−08
0.279523802
−0.128921833

ENSG00000125885
MCM8
1.20E−07
0.740692289
−0.028115948

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000051523
CYBA
1.00E−04
0.816434248
0.0204381

ENSG00000086504
MRPL28
1.00E−04
0.056394
−0.151444666

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000122882
ECD
1.00E−04
0.79331662
0.025252457

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000143401
ANP32E
1.00E−04
0.915890957
0.004516508

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000163808
KIF15
1.00E−04
0.593535319
0.070077932

ENSG00000166888
STAT6
1.00E−04
0.047894287
−0.21884119

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000105329
TGFB1
2.00E−04
0.015301045
−0.221315351

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000129317
PUS7L
2.00E−04
0.653028133
−0.054700064

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.586689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000177731
FLII
2.00E−04
0.139734019
0.11682969

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000111726
CMAS
2.01E−04
0.649986681
0.073406219

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000064490
RFXANK
3.00E−04
0.015800837
−0.324746409

ENSG00000100029
PES1
3.00E−04
0.805834098
−0.019606907

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.064932902

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMG5
3.00E−04
0.489633279
0.073022366

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000114867
EIF4G1
4.00E−04
0.49755475
0.028286796

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GMB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000114416
FXR1
6.00E−04
0.827823905
0.018508158

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000184661
CDCA2
6.00E−04
0.129977922
−0.116602274

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000100911
PSME2
6.11E−04
0.954296798
−0.00949908

ENSG00000101972
STAG2
7.00E−04
0.001047325
−0.187270211

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000171202
TMEM126A
8.07E−04
0.731670543
0.060950022

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

Table 7A-C. Motifs and G-quadruplexes in rDiff positive genes.

TABLE 7A

rDiff genes with 12-mer motif

Gene ID
Gene Name
Diff (p-value)
Translational Efficiency (p-value)
log2(Translational Efficiency)

ENSG00000088325
TPX2
4.00E−13
0.000751758
−0.147886462

ENSG00000055163
CYFIP2
6.00E−13
0.757974081
−0.02427969

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000181222
POLR2A
1.00E−12
0.038830003
−0.102840994

ENSG00000136068
FLNB
2.90E−12
0.062111584
−0.409977879

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−0.012039575

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−0.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−0.092503983

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−0.152181062

ENSG00000163655
GM PS
2.00E−11
0.775716157
0.020676052

ENSG00000086758
HUWE1
2.40E−11
0.464534104
−0.039863394

ENSG00000080345
RIF1
3.00E−11
0.722609171
0.022548991

ENSG00000078674
PCM1
5.00E−11
0.600752059
−0.058335335

ENSG00000131148
EMC8
5.00E−11
0.89007858
−0.019540666

ENSG00000198231
DDX42
6.00E−11
0.824728919
−0.015904689

ENSG00000165417
GTF2A1
7.00E−11
0.844760071
−0.015019218

ENSG00000104738
MCM4
1.00E−10
0.915393017
0.003107424

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000109111
NUP98
1.00E−10
0.656641011
−0.027832725

ENSG00000148773
MK167
1.00E−10
0.123777629
0.063404366

ENSG00000055483
USP36
2.00E−10
0.857880476
0.014047197

ENSG00000114126
TFDP2
7.00E−09
0.567162468
−0.026000796

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000054654
SYNE2
9.00E−09
0.143319349
−0.17547751

ENSG00000101191
DIDO1
9.00E−09
0.846657226
−0.024545447

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000099381
SETD1A
1.00E−08
0.334979113
0.098318494

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000125686
MED1
1.00E−08
0.18711587
−0.124662129

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000135905
DOCK10
1.00E−08
0.717332641
0.040604232

ENSG00000135932
CAB39
1.00E−08
0.019948395
−0.200243436

ENSG00000139218
SCAF11
1.00E−08
0.50709776
−0.04074801

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000167522
ANKRD11
1.00E−08
0.255387498
0.10026816

ENSG00000167670
CHAF1A
1.00E−08
0.388610811
−0.064999638

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000125651
GTF2F1
1.10E−08
0.031215966
−0.168644284

ENSG00000171298
GAA
1.10E−08
0.092998845
−0.248293341

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000110321
EIF4G2
2.00E−08
0.4789335
−0.030452093

ENSG00000128191
DGCR8
2.00E−08
0.071123809
−0.242947421

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000144580
RQCD1
2.00E−08
0.506022372
−0.045037202

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000113522
RAD50
4.00E−08
0.22034331
0.108849135

ENSG00000115806
GORASP2
4.00E−08
0.107877983
−0.140430182

ENSG00000104886
PLEKHJ1
6.00E−08
0.445334658
0.068851577

ENSG00000110367
DDX6
6.00E−08
0.469603134
−0.047598358

ENSG00000084733
RAB10
7.00E−08
0.078220422
−0.136343032

ENSG00000140829
DHX38
8.00E−08
0.404193545
−0.083781852

ENSG00000158985
CDC42SE2
8.00E−08
0.027991366
−0.145160094

ENSG00000070756
PABPC1
1.00E−07
0.067231582
−0.133311245

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000103495
MAZ
1.30E−07
0.642227894
0.032737594

ENSG00000080815
PSEN1
1.50E−07
0.468385762
−0.105188191

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000002822
MAD1L1
1.70E−07
0.758278428
−0.03032717

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000138668
HNRNPD
2.40E−07
0.003261874
−0.098862205

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000136104
RNASEH2B
4.20E−07
0.392137768
0.057232924

ENSG00000135679
MDM2
4.90E−07
0.948348125
0.012834459

ENSG00000179262
RAD23A
5.10E−07
0.674786887
0.038029829

ENSG00000071626
DAZAP1
5.20E−07
0.060128417
−0.110195121

ENSG00000197930
ERO1L
6.50E−07
0.973303548
−0.003430597

ENSG00000118816
CCNI
6.90E−07
0.001528498
−0.189161037

ENSG00000179409
GEMIN4
7.20E−07
0.143223537
−0.152149612

ENSG00000074603
DPP8
1.09E−06
0.371935225
−0.109929668

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000064419
TNPO3
1.00E−04
0.030219393
−0.182349237

ENSG00000068796
KIF2A
1.00E−04
0.056041279
0.123499472

ENSG00000077097
TOP2B
1.00E−04
0.84957972
0.01045839

ENSG00000100401
RANGAP1
1.00E−04
0.59275986
−0.053239149

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000107854
TNKS2
1.00E−04
0.358901659
0.113182695

ENSG00000110651
CD81
1.00E−04
0.010480682
−0.130640591

ENSG00000111642
CHD4
1.00E−04
0.289163376
0.048737019

ENSG00000124181
PLCG1
1.00E−04
0.95873485
−0.001417988

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000138496
PARP9
1.00E−04
0.385276066
0.103537296

ENSG00000139350
NEDD1
1.00E−04
0.725169134
0.037847451

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000141556
TBCD
1.00E−04
0.591494459
−0.026526545

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000151702
FLI1
1.00E−04
0.221034285
−0.138078723

ENSG00000156875
HIAT1
1.00E−04
0.380713082
−0.10910263

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000166747
AP1G1
1.00E−04
0.033859721
−0.180376252

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000205629
LCMT1
1.00E−04
0.552673909
−0.089560402

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000148334
PTGES2
1.04E−04
0.626929001
−0.068481398

ENSG00000055130
CUL1
2.00E−04
0.24134893
−0.116033963

ENSG00000077232
DNAJC10
2.00E−04
0.043053807
−0.322931196

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000103222
ABCC1
2.00E−04
0.969797812
0.002188323

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000110619
CARS
2.00E−04
0.186855283
0.157414334

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000140525
FANCI
2.00E−04
0.688024573
0.029180218

ENSG00000144554
FANCD2
2.00E−04
0.730926111
0.036291397

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000151502
VPS26B
2.00E−04
0.277634848
0.100319458

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000177731
FLIT
2.00E−04
0.139734019
0.11682969

ENSG00000196396
PTPN1
2.00E−04
0.634603291
0.040420571

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000072778
ACADVL
2.01E−04
0.634381953
0.052306846

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000185344
ATP6V0A2
2.03E−04
0.449082903
0.078626222

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000011295
TTC19
3.00E−04
0.726452954
0.048391976

ENSG00000036257
CUL3
3.00E−04
0.568119382
0.048886832

ENSG00000064115
TM7SF3
3.00E−04
0.921247137
0.007233323

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000167470
MIDN
3.00E−04
0.037975203
−0.404562969

ENSG00000167491
GATAD2A
3.00E−04
0.460886475
−0.052425426

ENSG00000169018
FEM1B
3.00E−04
0.01910054
−0.397020738

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000174238
PITPNA
3.00E−04
0.470422902
−0.066848619

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMGS
3.00E−04
0.489633279
0.073022366

ENSG00000205268
PDE7A
3.00E−04
0.558620633
−0.048541326

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000120738
EGR1
3.01E−04
0.317981925
−0.167567968

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000130402
ACTN4
3.01E−04
0.05655675
−0.168897398

ENSG00000073060
SCARB1
4.00E−04
0.444106259
−0.124760329

ENSG00000100242
SUN2
4.00E−04
0.443353969
0.107423956

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000119638
NEK9
4.00E−04
0.69912267
−0.04034303

ENSG00000140943
MBTPS1
4.00E−04
0.905572549
0.017038735

ENSG00000156983
BRPF1
4.00E−04
0.933570558
−0.010817335

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000072364
AFF4
4.01E−04
0.18444246
−0.147821651

ENSG00000198646
NCOA6
4.01E−04
0.116549501
−0.173636683

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000112200
ZNF451
5.00E−04
0.487557618
0.072986258

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000130816
DNMT1
5.00E−04
0.595705453
−0.027738247

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000100422
CERK
5.01E−04
0.767879843
−0.038668

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000033170
FUT8
6.00E−04
0.006226232
−0.355628717

ENSG00000063245
EPN1
6.00E−04
0.095672127
−0.260058118

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000115526
CHST10
6.00E−04
0.038600005
−0.351592853

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000184661
CDCA2
6.00E−04
0.129977922
−0.116602274

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000115020
PIKFYVE
7.00E−04
0.874274951
−0.045055571

ENSG00000120910
PPP3CC
7.00E−04
0.20233537
−0.200494687

ENSG00000133639
BTG1
7.00E−04
0.111632247
−0.307842825

ENSG00000143514
TP53BP2
7.00E−04
0.283581835
−0.117348193

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000169905
TOR1AIP2
7.00E−04
0.025144824
−0.223803399

ENSG00000102125
TAZ
7.01E−04
0.35021839
0.152681248

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000123983
ACSL3
7.01E−04
0.236015207
0.104976406

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000083312
TNPO1
8.00E−04
0.96323084
0.002633087

ENSG00000104472
CHRAC1
8.00E−04
0.353904047
0.105337178

ENSG00000105676
ARMC6
8.00E−04
0.830466125
−0.018392253

ENSG00000136824
SMC2
8.00E−04
0.373245909
0.054833376

ENSG00000168476
REEP4
8.00E−04
0.228797357
−0.127937767

ENSG00000173674
EIF1AX
8.00E−04
0.780846703
0.072635112

ENSG00000104852
SNRNP70
9.00E−04
0.594216034
−0.038334929

ENSG00000105486
LIG1
9.00E−04
0.865181674
−0.011170383

ENSG00000135521
LTV1
9.00E−04
0.577086029
0.047229663

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

ENSG00000185236
RAB11B
9.00E−04
0.250648111
−0.08681802

ENSG00000133961 NUMB 9.01E-04 0.646567716 0.059486807

TABLE 7B

rDiff genes with 9-mer motif

Gene ID
Gene Name
rDiff (p-value)
Translational Efficiency (p-value)
log2(Translational efficiency)

ENSG00000088325
TPX2
4.00E−13
0.000751758
−.147886462

ENSG00000055163
CYFIP2
6.00E−13
0.757974081
−0.02427969

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000181222
POLR2A
1.00E−12
0.038830003
−.102840994

ENSG00000136068
FLNB
2.90E−12
0.062111584
−.409977879

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−.012039575

ENSG00000055044
NOP58
1.00E−11
0.905915474
−.006508419

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−.092503983

ENSG00000108424
KPNB1
2.00E−11
8.66E−05
−.171777065

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−0.152181062

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000086758
HUWE1
2.40E−11
0.464534104
−0.039863394

ENSG00000080345
RIF1
3.00E−11
0.722609171
0.022548991

ENSG00000139687
RB1
4.00E−11
0.227456544
0.062123731

ENSG00000078674
PCM1
5.00E−11
0.600752059
−0.058335335

ENSG00000131148
EMC8
5.00E−11
0.89007858
−0.019540666

ENSG00000162607
USP1
5.00E−11
0.111472525
−0.094654587

ENSG00000198231
DDX42
6.00E−11
0.824728919
−0.015904689

ENSG00000165417
GTF2A1
7.00E−11
0.844760071
−0.015019218

ENSG00000087087
SRRT
1.00E−10
0.966692349
0.001824104

ENSG00000104738
MCM4
1.00E−10
0.915393017
0.003107424

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−0.157573098

ENSG00000110713
NUP98
1.00E−10
0.656641011
−0.027832725

ENSG00000148773
MK167
1.00E−10
0.123777629
0.063404366

ENSG00000174231
PRPF8
1.00E−10
0.595739886
0.019539188

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000140262
TCF12
2.00E−10
0.025334533
−0.184064816

ENSG00000197694
SPTAN1
2.00E−10
0.081327953
−0.18679623

ENSG00000087460
GNAS
3.00E−10
0.461136397
−0.032870857

ENSG00000104517
UBRS
3.00E−10
0.744729033
0.031234126

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−0.150308959

ENSG00000124789
NUP153
3.20E−10
0.677271772
−0.045251116

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−0.208903322

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−0.205302853

ENSG00000084093
REST
1.00E−09
0.221405653
−0.118069779

ENSG00000100554
ATP6V1D
1.00E−09
0.428461734
−0.082721884

ENSG00000101596
SMCHD1
1.00E−09
0.434566245
−0.059009881

ENSG00000125755
SYMPK
1.00E−09
0.552114085
−0.054422769

ENSG00000138795
LEF1
1.00E−09
1.60E−06
−0.210659864

ENSG00000172292
CERS6
1.00E−09
0.029552171
−0.205124483

ENSG00000198730
CTR9
1.00E−09
0.11470634
−0.142355213

ENSG00000013810
TACC3
2.00E−09
0.886452126
−0.009226853

ENSG00000066279
ASPM
2.00E−09
0.013635649
0.181712013

ENSG00000118193
KIF14
2.00E−09
0.302902759
0.10403347

ENSG00000137076
TLN1
2.00E−09
0.114582751
−0.09941367

ENSG00000143442
POGZ
2.00E−09
0.037681202
−0.207363006

ENSG00000151366
NDUFC2
2.00E−09
0.361312276
−0.043896664

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000165494
PCF11
2.00E−09
0.168402482
−0.149826279

ENSG00000204469
PRRC2A
2.00E−09
0.549464658
0.030387491

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000132646
PCNA
4.00E−09
0.449582299
0.020688405

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000197081
IGF2R
4.10E−09
0.531193218
0.066454289

ENSG00000134954
ETS1
5.70E−09
1.27E−05
−0.232324455

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000114126
TFDP2
7.00E−09
0.567162468
−0.026000796

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000054654
SYNE2
9.00E−09
0.143319349
−0.17547751

ENSG00000101191
DIDO1
9.00E−09
0.846657226
−0.024545447

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000099381
SETD1A
1.00E−08
0.334979113
0.098318494

ENSG00000099991
CABIN1
1.00E−08
0.104911155
−0.208959207

ENSG00000109332
UBE2D3
1.00E−08
0.601564183
0.04567695

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000125686
MED1
1.00E−08
0.18711587
−0.124662129

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000134313
KIDINS220
1.00E−08
0.857549373
0.021963698

ENSG00000135905
DOCK10
1.00E−08
0.717332641
0.040604232

ENSG00000135932
CAB39
1.00E−08
0.019948395
−0.200243436

ENSG00000139218
SCAF11
1.00E−08
0.50709776
−0.04074801

ENSG00000155827
RNF20
1.00E−08
0.674024322
0.06246891

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000167522
ANKRD11
1.00E−08
0.255387498
0.10026816

ENSG00000167670
CHAF1A
1.00E−08
0.388610811
−0.064999638

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000125651
GTF2F1
1.10E−08
0.031215966
−0.168644284

ENSG00000171298
GAA
1.10E−08
0.092998845
−0.248293341

ENSG00000175216
CKAP5
1.50E−08
0.03814885
0.117491174

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000084774
CAD
2.00E−08
0.242515439
0.087577807

ENSG00000110321
EIF4G2
2.00E−08
0.4789335
−0.030452093

ENSG00000128191
DGCR8
2.00E−08
0.071123809
−0.242947421

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000144580
RQCD1
2.00E−08
0.506022372
−0.045037202

ENSG00000171608
PIK3CD
2.00E−08
0.621359547
−0.054808961

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000164168
TMEM184C
2.50E−08
0.015050183
−0.397412646

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000108439
PNPO
3.00E−08
0.034630355
0.181670952

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000117906
RCN2
3.00E−08
0.060079639
0.177995705

ENSG00000130175
PRKCSH
3.00E−08
0.492538567
−0.034477239

ENSG00000136997
MYC
3.00E−08
0.000130485
−0.222358961

ENSG00000113522
RAD50
4.00E−08
0.22034331
0.108849135

ENSG00000115806
GORASP2
4.00E−08
0.107877983
−0.140430182

ENSG00000105677
TMEM147
5.00E−08
0.824197085
−0.020622451

ENSG00000135316
SYNCRIP
5.00E−08
0.141605449
−0.082838833

ENSG00000104886
PLEKHJ1
6.00E−08
0.445334658
0.068851577

ENSG00000110367
DDX6
6.00E−08
0.469603134
−0.047598358

ENSG00000188229
TUBB4B
6.00E−08
0.176644347
0.091849122

ENSG00000084733
RAB10
7.00E−08
0.078220422
−0.136343032

ENSG00000140829
DHX38
8.00E−08
0.404193545
−0.083781852

ENSG00000158985
CDC42SE2
8.00E−08
0.027991366
−0.145160094

ENSG00000166986
MARS
9.00E−08
0.040009981
−0.120193487

ENSG00000070756
PABPC1
1.00E−07
0.067231582
−0.133311245

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000103495
MAZ
1.30E−07
0.642227894
0.032737594

ENSG00000080815
PSEN1
1.50E−07
0.468385762
−0.105188191

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000002822
MAD1L1
1.70E−07
0.758278428
−0.03032717

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000120800
UTP20
1.80E−07
0.730921404
0.032446721

ENSG00000167747
C19orf48
1.80E−07
0.222151707
−0.136113219

ENSG00000132155
RAF1
1.90E−07
0.727868161
0.035824977

ENSG00000138668
HNRNPD
2.40E−07
0.003261874
−0.098862205

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000196230
TUBB
2.40E−07
0.534866787
0.035871882

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000198276
UCKL1
3.30E−07
0.304042297
−0.145350623

ENSG00000136104
RNASEH2B
4.20E−07
0.392137768
0.057232924

ENSG00000135679
MDM2
4.90E−07
0.948348125
0.012834459

ENSG00000179262
RAD23A
5.10E−07
0.674786887
0.038029829

ENSG00000071626
DAZAP1
5.20E−07
0.060128417
−0.110195121

ENSG00000115053
NCL
5.50E−07
0.060545427
0.042909924

ENSG00000197930
ERO1L
6.50E−07
0.973303548
−0.003430597

ENSG00000118816
CCNI
6.90E−07
0.001528498
−0.189161037

ENSG00000179409
GEMIN4
7.20E−07
0.143223537
−0.152149612

ENSG00000151694
ADAM17
7.30E−07
0.446223538
−0.1096626

ENSG00000074603
DPP8
1.09E−06
0.371935225
−0.109929668

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000132612
VPS4A
3.05E−06
0.187740524
−0.117542241

ENSG00000186480
INSIG1
3.08E−06
0.573173068
−0.037858571

ENSG00000149273
RPS3
2.35E−05
0.448604972
−0.041417003

ENSG00000038219
BOD1L1
1.00E−04
0.003376816
0.278967432

ENSG00000051523
CYBA
1.00E−04
0.816434248
0.0204381

ENSG00000068796
KIF2A
1.00E−04
0.056041279
0.123499472

ENSG00000072310
SREBF1
1.00E−04
0.744899078
−0.026352209

ENSG00000077097
TOP2B
1.00E−04
0.84957972
0.01045839

ENSG00000100401
RANGAP1
1.00E−04
0.59275986
−0.053239149

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000107854
TNKS2
1.00E−04
0.358901659
0.113182695

ENSG00000110651
CD81
1.00E−04
0.010480682
−0.130640591

ENSG00000111642
CHD4
1.00E−04
0.289163376
0.048737019

ENSG00000119041
GTF3C3
1.00E−04
0.862861391
0.021723507

ENSG00000124181
PLCG1
1.00E−04
0.95873485
−0.001417988

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000136758
YME1L1
1.00E−04
0.090002669
−0.100978955

ENSG00000139350
NEDD1
1.00E−04
0.725169134
0.037847451

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000141556
TBCD
1.00E−04
0.591494459
−0.026526545

ENSG00000142002
DPP9
1.00E−04
0.734190324
−0.049637386

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000156875
HIAT1
1.00E−04
0.380713082
−0.10910263

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000172775
FAM192A
1.00E−04
0.366617379
−0.209977577

ENSG00000178252
WDR6
1.00E−04
0.9305271
0.005862339

ENSG00000184432
COPB2
1.00E−04
0.99225242
0.000643147

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000205629
LCMT1
1.00E−04
0.552673909
−0.089560402

ENSG00000221829
FANCG
1.00E−04
0.38011695
0.102243151

ENSG00000038210
P14K2B
1.01E−04
0.689067203
0.060060784

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000106459
NRF1
1.01E−04
0.323046456
−0.119510858

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000148334
PTGES2
1.04E−04
0.626929001
−0.068481398

ENSG00000055130
CUL1
2.00E−04
0.24134893
−0.116033963

ENSG00000077232
DNAJC10
2.00E−04
0.043053807
−0.322931196

ENSG00000088247
KHSRP
2.00E−04
0.673716802
−0.021332247

ENSG00000089053
ANAPCS
2.00E−04
0.71210468
−0.020762022

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000103222
ABCC1
2.00E−04
0.969797812
0.002188323

ENSG00000105221
AKT2
2.00E−04
0.381664023
−0.141483695

ENSG00000105329
TGFB1
2.00E−04
0.015301045
−0.221315351

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000111906
HDDC2
2.00E−04
0.810276479
−0.022306759

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000144554
FANCD2
2.00E−04
0.730926111
0.036291397

ENSG00000145833
DDX46
2.00E−04
0.23392151
0.072701228

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000151502
VPS26B
2.00E−04
0.277634848
0.100319458

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000177731
FLI I
2.00E−04
0.139734019
0.11682969

ENSG00000196396
PTPN1
2.00E−04
0.634603291
0.040420571

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000111726
CMAS
2.01E−04
0.649986681
0.073406219

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000119403
PHF19
2.01E−04
0.072821269
0.168059289

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000100994
PYGB
2.02E−04
0.741200463
0.05467102

ENSG00000105401
CDC37
2.02E−04
0.182664767
0.098508161

ENSG00000185344
ATP6VOA2
2.03E−04
0.449082903
0.078626222

ENSG00000118007
STAG1
2.04E−04
0.802913841
−0.02813744

ENSG00000196700
ZNF512B
2.09E−04
0.699101376
0.063580592

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000011295
TTC19
3.00E−04
0.726452954
0.048391976

ENSG00000036257
CUL3
3.00E−04
0.568119382
0.048886832

ENSG00000064115
TM7SF3
3.00E−04
0.921247137
0.007233323

ENSG00000064490
RFXANK
3.00E−04
0.015800837
−0.324746409

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000124193
SRSF6
3.00E−04
0.119574817
0.116472581

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000137106
GRHPR
3.00E−04
0.415762699
−0.09172823

ENSG00000138081
FBXO11
3.00E−04
0.421443356
−0.098168828

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000167470
MIDN
3.00E−04
0.037975203
−0.404562969

ENSG00000167491
GATAD2A
3.00E−04
0.460886475
−0.052425426

ENSG00000169018
FEM1B
3.00E−04
0.01910054
−0.397020738

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000174238
PITPNA
3.00E−04
0.470422902
−0.066848619

ENSG00000175931
UBE2O
3.00E−04
0.447757287
0.068133312

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMGS
3.00E−04
0.489633279
0.073022366

ENSG00000205268
PDE7A
3.00E−04
0.558620633
−0.048541326

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000120738
EGR1
3.01E−04
0.317981925
−0.167567968

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000130402
ACTN4
3.01E−04
0.05655675
−0.168897398

ENSG00000131467
PSME3
3.01E−04
0.03715923
−0.116973165

ENSG00000154370
TRIM11
3.01E−04
0.010190424
−0.431525912

ENSG00000073060
SCARB1
4.00E−04
0.444106259
−0.124760329

ENSG00000093009
CDC45
4.00E−04
0.918341518
0.007977992

ENSG00000100242
SUN2
4.00E−04
0.443353969
0.107423956

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000104365
IKBKB
4.00E−04
0.474002406
0.087889302

ENSG00000105939
ZC3HAV1
4.00E−04
0.868091195
0.01093142

ENSG00000114867
EIF4G1
4.00E−04
0.49755475
0.028286796

ENSG00000115419
GLS
4.00E−04
0.000197719
−0.269875671

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000119638
NEK9
4.00E−04
0.69912267
−0.04034303

ENSG00000140943
MBTPS1
4.00E−04
0.905572549
0.017038735

ENSG00000156983
BRPF1
4.00E−04
0.933570558
−0.010817335

ENSG00000172795
DCP2
4.00E−04
0.294839777
0.094471533

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000072364
AFF4
4.01E−04
0.18444246
−0.147821651

ENSG00000135763
URB2
4.01E−04
0.668047421
0.04463194

ENSG00000198646
NCOA6
4.01E−04
0.116549501
−0.173636683

ENSG00000186716
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000216490
IFI30
4.13E−04
0.518872644
−0.117960608

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000112200
ZNF451
5.00E−04
0.487557618
0.072986258

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

ENSG00000130816
DNMT1
5.00E−04
0.595705453
−0.027738247

ENSG00000132842
AP3B1
5.00E−04
0.894277559
0.020029663

ENSG00000138698
RAP1GDS1
5.00E−04
0.715002624
−0.035260421

ENSG00000167323
STIM1
5.00E−04
0.977475163
0.002228555

ENSG00000174579
MSL2
5.00E−04
0.027763257
−0.205275001

ENSG00000185262
UBALD2
5.00E−04
0.504061449
0.054009121

ENSG00000186575
NF2
5.00E−04
0.511808
0.06843328

ENSG00000100422
CERK
5.01E−04
0.767879843
−0.038668

ENSG00000102908
NFAT5
5.01E−04
0.225277986
−0.178477519

ENSG00000005955
GGNBP2
6.00E−04
0.626526855
−0.042670122

ENSG00000033170
FUT8
6.00E−04
0.006226232
−0.355628717

ENSG00000060491
OGFR
6.00E−04
0.881572577
−0.018437371

ENSG00000063245
EPN1
6.00E−04
0.095672127
−0.260058118

ENSG00000067225
PKM
6.00E−04
0.089243304
0.079429696

ENSG00000090372
STRN4
6.00E−04
0.942223216
0.00735298

ENSG00000115526
CHST10
6.00E−04
0.038600005
−0.351592853

ENSG00000132466
ANKRD17
6.00E−04
0.746590296
0.023300227

ENSG00000197323
TRIM33
6.00E−04
0.267737397
−0.112414388

ENSG00000198728
LDB1
6.00E−04
0.333004346
−0.147406224

ENSG00000033800
PIAS1
6.01E−04
0.942720076
0.005741934

ENSG00000075975
MKRN2
6.01E−04
0.98382419
0.004421651

ENSG00000109062
SLC9A3R1
6.01E−04
0.122301958
−0.064055136

ENSG00000167775
CD320
6.01E−04
0.822695325
0.022736769

ENSG00000197312
DDI2
6.01E−04
0.856181146
−0.025215686

ENSG00000011376
LARS2
6.02E−04
0.269847002
−0.142543886

ENSG00000104695
PPP2CB
7.00E−04
0.032333256
−0.321922476

ENSG00000115020
PIKFYVE
7.00E−04
0.874274951
−0.045055571

ENSG00000116133
DHCR24
7.00E−04
0.242618057
−0.119340931

ENSG00000120910
PPP3CC
7.00E−04
0.20233537
−0.200494687

ENSG00000133639
BTG1
7.00E−04
0.111632247
−0.307842825

ENSG00000143514
TP53BP2
7.00E−04
0.283581835
−0.117348193

ENSG00000165209
STRBP
7.00E−04
0.030348179
−0.279083308

ENSG00000169905
TOR1AIP2
7.00E−04
0.025144824
−0.223803399

ENSG00000021762
OSBPLS
7.01E−04
0.905417327
−0.030769757

ENSG00000102125
TAZ
7.01E−04
0.35021839
0.152681248

ENSG00000111737
RAB35
7.01E−04
0.267070813
−0.097986528

ENSG00000123983
ACSL3
7.01E−04
0.236015207
0.104976406

ENSG00000123213
NLN
7.02E−04
0.499519365
0.090955024

ENSG00000060237
WNK1
8.00E−04
0.614924113
−0.029766546

ENSG00000082212
ME2
8.00E−04
0.795777072
−0.028699073

ENSG00000083312
TNPO1
8.00E−04
0.96323084
0.002633087

ENSG00000104472
CHRAC1
8.00E−04
0.353904047
0.105337178

ENSG00000105676
ARMC6
8.00E−04
0.830466125
−0.018392253

ENSG00000138231
DBR1
8.00E−04
0.870540124
0.016538189

ENSG00000168476
REEP4
8.00E−04
0.228797357
−0.127937767

ENSG00000169221
TBC1DOB
8.00E−04
0.845261963
0.037666933

ENSG00000173674
EIF1AX
8.00E−04
0.780846703
0.072635112

ENSG00000177156
TALDO1
8.00E−04
0.975031972
−0.001808282

ENSG00000204713
TRIM27
8.00E−04
0.790207031
−0.026814299

ENSG00000139946
PELI2
8.01E−04
0.84869402
−0.030488571

ENSG00000174010
KLHL15
8.01E−04
0.770357983
−0.039693382

ENSG00000171861
RNMTL1
8.04E−04
0.07761122
0.249083661

ENSG00000171202
TMEM126A
8.07E−04
0.731670543
0.060950022

ENSG00000081791
KIAA0141
9.00E−04
0.905406058
−0.017374448

ENSG00000104852
SNRNP70
9.00E−04
0.594216034
−0.038334929

ENSG00000105486
LIG1
9.00E−04
0.865181674
−0.011170383

ENSG00000115761
NOL10
9.00E−04
0.442727268
0.090675848

ENSG00000136709
WDR33
9.00E−04
0.304508163
−0.081701638

ENSG00000180104
EXOC3
9.00E−04
0.538380165
−0.070376673

ENSG00000184719
RNLS
9.00E−04
0.124096231
−0.160207128

ENSG00000185236
RAB11B
9.00E−04
0.250648111
−0.08681802

ENSG00000133961
NUMB
9.01E−04
0.646567716
0.059486807

TABLE 7C

rDiff genes with G-Quadruplex structure

Gene ID
Gene Name
rDiff (p-value)
Translational Efficiency (p-value)
log2(Translational Efficiency)

ENSG00000009954
BAZ1B
1.00E−12
0.813245824
0.011597992

ENSG00000139613
SMARCC2
1.00E−12
0.334491125
0.087836839

ENSG00000127616
SMARCA4
3.00E−12
0.813848874
−.012039575

ENSG00000100796
SMEK1
1.00E−11
0.021404696
−.176469607

ENSG00000130726
TRIM28
1.00E−11
0.034098412
−.092503983

ENSG00000130724
CHMP2A
2.00E−11
0.770037849
0.028723436

ENSG00000152601
MBNL1
2.00E−11
0.00777836
−.152181062

ENSG00000163655
GMPS
2.00E−11
0.775716157
0.020676052

ENSG00000198231
DDX42
6.00E−11
0.824728919
−.015904689

ENSG00000105063
PPP6R1
1.00E−10
0.029786388
−.157573098

ENSG00000109111
SUPT6H
2.00E−10
0.994134615
0.001145357

ENSG00000104517
UBR5
3.00E−10
0.744729033
0.031234126

ENSG00000171681
ATF7IP
3.00E−10
0.209720012
−.150308959

ENSG00000137845
ADAM10
9.00E−10
0.012053048
−.208903322

ENSG00000058668
ATP2B4
1.00E−09
0.000680955
−.302809666

ENSG00000082641
NFE2L1
1.00E−09
0.267959196
−.205302853

ENSG00000125755
SYM PK
1.00E−09
0.552114085
−.054422769

ENSG00000172292
CERS6
1.00E−09
0.029552171
−.205124483

ENSG00000013810
TACC3
2.00E−09
0.886452126
−.009226853

ENSG00000066279
ASPM
2.00E−09
0.013635649
0.181712013

ENSG00000164190
NIPBL
2.00E−09
0.303068767
−0.09710725

ENSG00000117713
ARID1A
2.10E−09
0.944760522
0.009363654

ENSG00000153827
TRIP12
2.80E−09
0.04819259
−0.171340571

ENSG00000164134
NAA15
4.00E−09
0.476257503
−0.043457933

ENSG00000149480
MTA2
6.00E−09
2.64E−05
−0.22354576

ENSG00000120733
KDM3B
8.00E−09
0.056284307
−0.188410685

ENSG00000184009
ACTG1
9.00E−09
0.153012011
0.060571337

ENSG00000068024
HDAC4
1.00E−08
0.08742941
−0.17058278

ENSG00000106628
POLD2
1.00E−08
0.658612976
−0.035385479

ENSG00000118482
PHF3
1.00E−08
0.873633816
0.012763981

ENSG00000127152
BCL11B
1.00E−08
5.40E−10
−0.517770746

ENSG00000163466
ARPC2
1.00E−08
0.883580647
0.005900615

ENSG00000173020
ADRBK1
1.00E−08
0.708537254
−0.02554542

ENSG00000108021
FAM208B
1.70E−08
0.236407718
−0.130316925

ENSG00000065613
SLK
2.00E−08
0.412051605
−0.115711529

ENSG00000092094
OSGEP
2.00E−08
0.977762307
−0.002519015

ENSG00000136878
USP20
2.00E−08
0.019165529
−0.206602358

ENSG00000140332
TLE3
2.00E−08
0.001343794
−0.227829431

ENSG00000171608
PIK3CD
2.00E−08
0.621359547
−0.054808961

ENSG00000123066
MED13L
2.20E−08
4.79E−05
−0.415941737

ENSG00000048405
ZNF800
3.00E−08
0.020652909
−0.271097499

ENSG00000116698
SMG7
3.00E−08
0.886915303
−0.013938554

ENSG00000102606
ARHGEF7
6.00E−08
0.279523802
−0.128921833

ENSG00000125885
MCM8
1.20E−07
0.740692289
−0.028115948

ENSG00000171310
CHST11
1.20E−07
0.004536717
−0.14604981

ENSG00000184007
PTP4A2
1.50E−07
0.00039459
−0.142942918

ENSG00000071564
TCF3
1.70E−07
0.851040343
−0.020991025

ENSG00000171522
PTGER4
2.40E−07
0.002288634
−0.274827847

ENSG00000106609
TMEM248
2.90E−07
0.005316307
−0.23621242

ENSG00000079805
DNM2
1.53E−06
0.594275253
−0.034637408

ENSG00000051523
CYBA
1.00E−04
0.816434248
0.0204381

ENSG00000086504
MRPL28
1.00E−04
0.056394
−0.151444666

ENSG00000104613
INTS10
1.00E−04
0.796914737
0.022823898

ENSG00000122882
ECD
1.00E−04
0.79331662
0.025252457

ENSG00000136653
RASSF5
1.00E−04
0.545754108
−0.05276974

ENSG00000141027
NCOR1
1.00E−04
0.129071822
−0.136116164

ENSG00000143401
ANP32E
1.00E−04
0.915890957
0.004516508

ENSG00000143870
PDIA6
1.00E−04
0.042049362
0.102641235

ENSG00000157593
SLC35B2
1.00E−04
0.149940449
−0.2407324

ENSG00000160796
NBEAL2
1.00E−04
0.231202003
0.128523719

ENSG00000163808
KIF15
1.00E−04
0.593535319
0.070077932

ENSG00000166888
STAT6
1.00E−04
0.047894287
−0.21884119

ENSG00000167978
SRRM2
1.00E−04
0.027585188
−0.081656945

ENSG00000198911
SREBF2
1.00E−04
0.382129128
−0.081310955

ENSG00000204227
RING1
1.00E−04
0.123205251
−0.184910275

ENSG00000104825
NFKBIB
1.01E−04
0.438223723
0.114649527

ENSG00000125484
GTF3C4
1.01E−04
0.265749952
−0.128337377

ENSG00000089234
BRAP
2.00E−04
0.93786126
−0.010542696

ENSG00000105329
TGFB1
2.00E−04
0.015301045
−0.221315351

ENSG00000108175
ZMIZ1
2.00E−04
0.05690215
−0.222817452

ENSG00000129317
PUS7L
2.00E−04
0.653028133
−0.054700064

ENSG00000131504
DIAPH1
2.00E−04
0.005406879
−0.213577391

ENSG00000135090
TAOK3
2.00E−04
0.163787333
−0.139600964

ENSG00000147650
LRP12
2.00E−04
0.590549253
0.057987792

ENSG00000153310
FAM49B
2.00E−04
0.007506383
−0.139159484

ENSG00000160877
NACC1
2.00E−04
0.286689117
−0.119046325

ENSG00000163349
HIPK1
2.00E−04
0.020020123
−0.282659771

ENSG00000163904
SENP2
2.00E−04
0.045589218
−0.287466993

ENSG00000177731
FLII
2.00E−04
0.139734019
0.11682969

ENSG00000257103
LSM14A
2.00E−04
0.836442459
−0.017136198

ENSG00000111726
CMAS
2.01E−04
0.649986681
0.073406219

ENSG00000113580
NR3C1
2.01E−04
0.497681416
0.120970261

ENSG00000130311
DDA1
2.01E−04
0.855575658
−0.028673083

ENSG00000005007
UPF1
3.00E−04
0.109682217
−0.088407059

ENSG00000064490
RFXANK
3.00E−04
0.015800837
−0.324746409

ENSG00000100029
PES1
3.00E−04
0.805834098
−0.019606907

ENSG00000107164
FUBP3
3.00E−04
0.891753365
−0.016568849

ENSG00000112308
C6orf62
3.00E−04
0.221892591
−0.102283924

ENSG00000134371
CDC73
3.00E−04
0.078009542
−0.179882162

ENSG00000142453
CARM1
3.00E−04
0.397417148
−0.08333644

ENSG00000173442
EHBP1L1
3.00E−04
0.648913241
0.061932902

ENSG00000176619
LMNB2
3.00E−04
0.831805089
0.019798531

ENSG00000198952
SMG5
3.00E−04
0.489633279
0.073022366

ENSG00000214078
CPNE1
3.00E−04
0.910315945
−0.012942408

ENSG00000129355
CDKN2D
3.01E−04
0.933543847
−0.011782808

ENSG00000100697
DICER1
4.00E−04
0.937569952
0.007626111

ENSG00000114867
EIFG1
4.00E−04
0.49755475
0.028286796

ENSG00000115694
STK25
4.00E−04
0.063817944
−0.233874856

ENSG00000198087
CD2AP
4.00E−04
0.957505459
−0.006300497

ENSG00000167323
BCR
4.02E−04
0.28449305
−0.206113331

ENSG00000058063
ATP11B
5.00E−04
0.340893448
0.106997948

ENSG00000078369
GNB1
5.00E−04
0.011642786
−0.133797709

ENSG00000078618
NRD1
5.00E−04
0.441231318
−0.057082496

ENSG00000106290
TAF6
5.00E−04
0.014175182
−0.210235711

ENSG00000115548
KDM3A
5.00E−04
0.40321263
0.088419558

	Number	Date	Country
Parent	PCT/US14/68875	Dec 2014	US
Child	14693832		US

METHODS FOR IDENTIFYING ANTI-CANCER COMPOUNDS

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

CROSS-REFERENCE TO RELATED APPLICATIONS

GOVERNMENT SUPPORT

Provisional Applications (1)

Continuation in Parts (1)