MODULATING IMMUNE RESPONSE VIA TARGETING OF OLFACTORY RECEPTOR ACTIVITY

SUMMARY OF INVENTION

There is presently provided novel regulators of immune response and methods of modulating the novel regulators to modulate an immune response. The present invention identifies olfactory receptors in macrophages, monocytes and dendritic cells that can be targeted to modulate immune responses, including innate immune responses. In particular embodiments of the present invention, the olfactory receptors identified are present on macrophages (e.g. vascular macrophages) and their expression, activity, or binding can be targeted to modulate cardiovascular disease, atherosclerosis, infection, or cancer.

Thus, in one aspect, there is provided a method of modulating an immune response, the method comprising modulating expression or activity of one or more olfactory receptors. In another aspect, there is provided a method of modulating an adverse cardiovascular event or cardiovascular disease, the method comprising modulating expression or activity of one or more olfactory receptors. In an additional aspect, there is provided a method of modulating atherosclerosis, the method comprising modulating expression or activity of one or more olfactory receptors. In another aspect, there is provided a method of modulating a viral, bacterial or fungal infection, neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, the method comprising modulating expression or activity of one or more olfactory receptors. In certain embodiments, the method comprises decreasing, reducing, inhibiting, suppressing, limiting or controlling expression or activity of one or more olfactory receptors. In other embodiments, the method comprises enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptors.

In an additional aspect, there is provided a method of modulating an immune response, the method comprising modulating expression or activity of one or more olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In specific embodiments, the one or more olfactory receptors includes Olfr2. In certain embodiments, the method comprises decreasing, reducing, inhibiting, suppressing, limiting or controlling expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In certain embodiments, the method comprises decreasing, reducing, inhibiting, suppressing, limiting or controlling expression or activity of one or more olfactory receptor listed in any of FIGS. 2A and 2B. In other embodiments, the method comprises enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In other embodiments, the method comprises enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptor listed in any of FIGS. 2A and 2B.

In another aspect, there is provided a method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation in a subject, comprising modulating expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In yet another aspect, there is provided a method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation in a subject, comprising modulating expression or activity of one or more olfactory receptor listed in any of FIGS. 2A and 2B. In yet another aspect, there is provided a method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, comprising modulating expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In yet another aspect, there is provided a method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, comprising modulating expression or activity of one or more olfactory receptor listed in any of FIGS. 2A and 2B.

In certain embodiments, the methods comprise decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, comprising modulating expression or activity of one or more olfactory receptors. In different embodiments, the methods comprise decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, comprising modulating expression or activity of one or more olfactory receptors.

In some embodiments, the method comprises one or more of reducing, inhibiting, suppressing, limiting, controlling, enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptors. In certain embodiments, the reducing, inhibiting, suppressing, limiting, controlling, enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptors comprises reducing, inhibiting, suppressing, limiting, controlling, enhancing, stimulating, or inducing signaling through olfactory receptors and/or the respective downstream signaling effects of reducing, inhibiting, suppressing, limiting, controlling, enhancing, stimulating, inducing or increasing expression or activity of olfactory receptors. Certain alternative embodiments comprise decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, or an adverse symptom of the autoimmune response, disorder or disease. In certain embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8 and Table 9. In certain embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of FIGS. 2A and 2B. In some embodiments, such adverse symptoms of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an adverse symptom of the autoimmune response, disorder or disease include but are not limited to swelling, pain, rash, headache, fever, nausea, diarrhea, bloat, lethargy, skeletal joint stiffness or tissue or cell damage. In different embodiments, the adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or the adverse symptom of the autoimmune response, disorder or disease is chronic or acute. In certain embodiments, the subject is in need of treatment for or is at risk of an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an autoimmune response, disorder or disease. The immune disorder, inflammatory response, inflammation, autoimmune response disorder or autoimmune disease of the present methods include but are not limited rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

In another aspect, there is provided a method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse cardiovascular event or cardiovascular disease, comprising modulating expression or activity of one or more olfactory receptors. In some embodiments, the adverse cardiovascular event or cardiovascular disease includes but is not limited to coronary artery disease, peripheral artery disease, cerebrovascular disease, renal artery disease, stroke, myocardial infarction (heart attack), ischemic heart failure, transient ischemic attack or brain trauma, atherosclerotic plaque formation or elevated blood cholesterol. In another aspect, there is provided a method decreasing, reducing, inhibiting, suppressing, limiting or controlling atherosclerosis, comprising modulating expression or activity of one or more olfactory receptors. In some embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In some embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of FIGS. 2A and 2B.

In another aspect, there is provided a method of reducing or inhibiting in a subject a neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, the method comprising modulating expression or activity of one or more olfactory receptors. In some embodiments, modulating expression or activity of one or more olfactory receptors comprises administering an agonist of one or more olfactory receptors. In another aspect, there is provided a method of reducing or inhibiting in a subject a neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, the method comprising increasing expression or activity of one or more olfactory receptors. In some embodiments, increasing expression or activity of one or more olfactory receptors comprises administering an agonist of one or more olfactory receptors. In yet another aspect, there is provided a method of reducing or inhibiting in a subject viral, bacterial or fungal infection, the method comprising modulating expression or activity of one or more olfactory receptors. In different embodiments, these methods comprise one or more of reducing, inhibiting, suppressing, limiting, controlling enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptors. In some embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In some embodiments, the one or more olfactory receptors are selected from the olfactory receptors listed in any of FIGS. 2A and 2B. In some embodiments, the agonist is one or more of the agonists listed in Table 8.

In certain embodiments, the methods comprise decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, or viral, bacterial or fungal infection. The neoplasia, neoplastic disorder, tumor, cancer or malignancy of the methods provided herein include but are not limited to a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma; or a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.

In certain embodiments of the present invention, the methods comprise modulating an innate immune response in the subject. In some embodiments, the methods comprise modulating the activity of a macrophage. In alternative embodiments, the macrophage is a vascular macrophage.

In another aspect, there is provided a method for modulating expression or activity of one or more olfactory receptors comprising modulating the binding of the olfactory receptor to a ligand. In some embodiments, the modulating of the binding of the olfactory receptor to a ligand comprises inhibiting binding of the ligand to the olfactory receptor. In certain alternative embodiments, the modulating of the binding of the olfactory receptor to a ligand comprises agonizing binding of the ligand to the olfactory receptor.

In particular embodiments, the methods of the present invention comprise administering to the subject a therapeutically effective amount of an agent that modulates expression or activity of one or more olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. Alternatively, the methods of the present invention comprise administering to the subject a therapeutically effective amount of an agent that modulates expression or activity of one or more olfactory receptors listed in any of FIGS. 2A and 2B. In different embodiments, the agent is an antagonist or agonist of expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9. In certain alternative embodiments, the antagonist or agonist is one or more of the agonists listed in Table 8 or the antagonists listed in Table 9. In different embodiments, the agent is an antagonist or agonist of expression or activity of one or more olfactory receptor listed in any of FIGS. 2A and 2B. In certain embodiments, the agent is a protein, a peptide, an antibody, an siRNA, a small molecule or a ligand mimetic.

In some embodiment of the present methods, the subject is a mammal, including but not limited to a human.

In another aspect, there is provided a method of modulating an immune response in a subject, comprising modulating expression or activity of one or more olfactory receptors (OLFR).

In some embodiments, the OLFR is expressed by a cell in vivo. In some embodiments, the cell is an animal cell, with the proviso that the cell is not an olfactory cell. In some embodiments, the cell is a macrophage. In some embodiments, the macrophage is a vascular macrophage.

In some embodiments, the modulation comprises one or more of inhibiting, decreasing, reducing, suppressing, limiting or controlling the immune response by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.

In some embodiments, the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.

In some embodiments, the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.

In some embodiments, the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, or an adverse symptom of the autoimmune response, disorder or disease in the subject.

In some embodiments, the adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an adverse symptom of the autoimmune response, disorder or disease is swelling, pain, rash, headache, fever, nausea, diarrhea, bloat, lethargy, skeletal joint stiffness or tissue or cell damage. In some embodiments, the adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or the adverse symptom of the autoimmune response, disorder or disease is chronic or acute.

In some embodiments, immune disorder, inflammatory response, inflammation, autoimmune response disorder or autoimmune disease comprises rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

In some embodiments, the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse cardiovascular event or cardiovascular disease by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR. In some embodiments, the adverse cardiovascular event or cardiovascular disease comprises coronary artery disease, peripheral artery disease, cerebrovascular disease, renal artery disease, stroke, myocardial infarction (heart attack), ischemic heart failure, transient ischemic attack or brain trauma, atherosclerosis, atherosclerotic plaque formation or elevated blood cholesterol.

In some embodiments, the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling atherosclerosis, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.

In some embodiments, the method comprises one or more of reducing or inhibiting in a subject viral, bacterial or fungal infection, by a method comprising administering to the subject an effective amount of an agent that increases the expression of or activates the OLFR.

In some embodiments, the modulation comprises one or more of comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, or viral, bacterial or fungal infection by a method comprising administering to the subject an effective amount of an agent that increases the expression of or activates the OLFR. In some embodiments, the neoplasia, neoplastic disorder, tumor, cancer or malignancy treated is a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma; or a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.

In some embodiments, the OLFR is an OLFR listed in any one of Tables 1-9, and FIGS. 2A and 2B. In some embodiments, the OLFR is an OLFR listed in Table 7. In some embodiments, the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.

In some embodiments, the agent is selected from the group of: a ligand or small molecule that binds to the OLFR or blocks the binding of the OLFR to the ligand or an agent that inhibits the expression of the OLFR by the cell. In some embodiments, the agent is selected from the group of an antibody, fragment or mimetic that binds to OLFR or an OLFR ligand, an anti-OLFR gene silencing agent, octanal, heptanal, or a prodrug or solvate thereof.

In some embodiments, the agent modulates the OLFR by modulating the trafficking of the OLFR to a plasma membrane of a cell. In some embodiments, the agent is a protein selected from the group of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), or guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). In some embodiments, the agent is a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

In some embodiments, the immune response is stimulated by a method comprising administering an agent that increases expression or secretion of an inflammatory cytokine. In some embodiments, the inflammatory cytokine is selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2).

In another aspect, there is provided a method of suppressing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR), thereby suppressing an immune response in the subject.

In some embodiments, the OLFR is an OLFR listed in any one of Tables 1-9. In some embodiments, the OLFR is an OLFR listed in Table 7. In some embodiments, the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.

In some embodiments, the agent is a gene silencing agent. In some embodiments, the gene silencing agent is selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. In some embodiments, the RNAi molecule is selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA).

In some embodiments, the agent decreases the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. In some embodiments, the ligand is an OLFR ligand listed in Table 8.

In some embodiments, the agent is an OLFR antagonist. In some embodiments, the OLFR antagonist is citral, undecanal, oxyphenylon, phenirat, methyl cinnamaldehyde, hydrocinamaldehyde, bourgeonal, ethylhexanoic acid, α-ionone, octanoic acid, a solvate or prodrug thereof. In some embodiments, the OLFR antagonist is an antagonist listed in Table 9.

In some embodiments, the agent decreases the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.

In some embodiments, the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.

In another aspect, there is provided a method of suppressing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby suppressing an immune response in the subject.

In another aspect, there is provided a method of treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR). In another aspect, there is provided a method of treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.

In another aspect, there is provided a method of treating a cardiovascular disease in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR). In another aspect, there is provided a method of a cardiovascular disease in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.

In another aspect, there is provided a method of increasing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby increasing an immune response in the subject.

In another aspect, there is provided a method of treating an infection in a subject in need thereof, the method comprising administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR). In another aspect, there is provided a method of treating an infection in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. In some embodiments, the infection is selected from the group consisting of a viral infection, bacterial infection, or fungal infection.

In another aspect, there is provided a method of treating cancer in a subject in need thereof, the method comprising administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR). In another aspect, there is provided a method of cancer in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.

In another aspect, there is provided a method of modulating the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that modulates the expression or activity of an olfactory receptor (OLFR). In some embodiments, the agent increases the expression of or activates the OLFR. In other embodiments, the agent decreases the expression or activity of the OLFR.

In another aspect, there is provided a method of increasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that increases the expression of or activates an olfactory receptor (OLFR).

In another aspect, there is provided a method of decreasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that decreases the expression of or inhibits an olfactory receptor (OLFR).

In another aspect, there is provided a method of modulating the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that modulates the trafficking of an olfactory receptor (OLFR) to a plasma membrane of the cell. In some embodiments, the agent increases or promotes the trafficking of the OLFR to the plasma membrane of the cell. In some embodiments, the agent decreases or inhibits the trafficking of the OLFR to the plasma membrane of a cell.

In another aspect, there is provided a method of increasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of the cell.

In another aspect, there is provided a method of decreasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that decreases or inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.

In some embodiments, the methods comprise the use of one or more agents. In some embodiments, the agent is a gene silencing agent. In some embodiments, the gene silencing agent is selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. In some embodiments, the RNAi molecule is selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA).

In some embodiments, the agent decreases the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. In some embodiments, the ligand is an OLFR ligand listed in Table 8.

In some embodiments, the agent decreases the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.

In some embodiments, the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.

In some embodiments, the agent is an OLFR agonist. In some embodiments, the OLFR agonist is an agonist listed in Table 8. In some embodiments, the OLFR agonist is selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, decyl aldehyde. In some embodiments, the agent is octanal, heptanal, or a prodrug or solvate thereof.

In some embodiments, the agent is a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). In some embodiments, the agent comprises a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

In some embodiments, the OLFR is an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B. In some embodiments, the OLFR is an OLFR listed in Table 7. In some embodiments, the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.

In some embodiments, the one or more proteins involved in an immune response is any of the proteins shown in FIGS. 16 and 17. In some embodiments, the one or more proteins involved in an immune response is a protein selected from CCL5 (C-C Motif Chemokine Ligand 5), Tnfrsf12a (Osteoprotegerin), Axin 1, Nadk, Ahr (Aryl hydrocarbon receptor), QDPR (quinoid dihydropteridine reductase), HGF (Hepatocyte Growth Factor), ADAM23, or Snap29.

In some embodiments, the administration is local or systemic. In some embodiments, the administration comprises by a method comprising intravenously.

In some embodiments, the subject is a mammal. In some embodiments, the subject has or is predisposed to a disease or disorder involving an immune dysregulation. In some embodiments, the subject is a human patient.

In another aspect, there is provided a kit comprising an agent that modulates the activity of an OLFR and instructions for use.

In some embodiments, the agent modulates the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. In some embodiments, the ligand is an OLFR ligand listed in Table 8.

In some embodiments, the agent modulates the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.

In some embodiments, the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.

In some embodiments, wherein the OLFR is an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B. In some embodiments, the OLFR is an OLFR listed in Table 7. In some embodiments, the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.

All features of exemplary embodiments which are described in this disclosure and are not mutually exclusive can be combined with one another. Elements of one embodiment can be utilized in the other embodiments without further mention. Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments in conjunction with the accompanying Figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-C show a non-limiting example of Olfr2 inhibition with Citral and the resulting decrease in inflammatory gene expression and atherosclerosis progression in vivo. FIG. 1A shows the results of a gene expression analysis of CCL2, CCL4, TNF and iNOS after treatment with the Olfr2 inhibitor citral alone or in combination with octanal and LPS. FIG. 1B shows the results of an atherosclerosis lesion evaluation (% and number of pixels with lesions) after the treatment with OLFR2 inhibitor citral. FIG. 1C shows pictures of pinned aortas of mice treated with citral or saline (untreated).

FIG. 2A depicts a heat map of Olfr genes (total 1123) expressed in mouse vascular macrophages and several other tissue macrophages, DCs and blood monocytes.

FIG. 2B displays a heat map of expressed Olfrs with known human orthologues.

FIG. 3A shows the relative expression of Olfr2 quantified by real time PCR analysis of Olfr2 expression normalized to expression of Gapdh and untreated control.

FIG. 3B shows Olfr2 protein expression in BMDM lysate.

FIGS. 3C-D show flow cytometric analysis of extracellular Olfr2 expression. Median Fluorescence Intensity (MFI) of live F4/80⁺ BMDMs is reported.

FIG. 3E shows Airyscan high resolution imaging of previously treated BMDMs stained for Olfr2 (AF488). Hoechst was used for the nuclear staining Scale bar=200 mm.

FIG. 3F shows Olfr2 expression was determined by real-time PCR.

FIGS. 3G-H show flow cytometric analysis of Olfr2 by aortic macrophages. Olfr2 Median Fluorescence Intensity (MFI) of vascular macrophages (CD45⁺, Live, TCRβ⁻, CD19⁻, F4/80⁺) is reported. (n=5-6/group).

FIG. 3I shows microphotographs depicting Olfr2, CD68 and Hoechst immunoreactivity in whole mount aorta from Apoe^−/−mouse fed WD for 2 weeks. Right: Zoom in of Olfr2⁺ CD68⁺ macrophages. Data are presented as mean±SEM. *p<0.05, ** p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test.

FIGS. 4A-B show Rtp1 (FIG. 4A) and Rtp2 (FIG. 4B) expression in aorta as measured by qPCR.

FIGS. 5A-B show Olfr2 expression in T cells and B cells from whole digested aorta.

FIG. 6A show Olfr2 expression on blood mononuclear cells.

FIG. 6B shows Olfr2 function on blood mononuclear cells.

FIGS. 7A-G show that Olfr2 ligation induces an inflammatory response by vascular macrophages. FIG. 7A) Ca²⁺ signals of Ctrl and Oct are displayed as a dot plot. FIG. 7B) Time point analyzed Fluo-4 Median Fluorescence Intensity (MFI). SD is calculated among the cells for each time point. (n=20-50). FIG. 7C) Oct induces pro-inflammatory gene expression in aorta. FIG. 7D) Cit (100 μM) reduced octanal induced expression of Ccl2, Ccl4, Tnf, and Nos2 in aortas. (n=5-6/group). FIG. 7E) CCL2, CCL4, and TNF protein quantification by cytokine bead arrays and flow cytometry in supernatants of stimulated aortas. FIG. 7F) Intracellular TNF expression in F4/80⁺ vascular macrophages, displayed as MFI. FIG. 7G) BMDMs were treated with LPS (50 ng/mL) for 18 h and subsequently stimulated with Oct and Cit alone or both combined.

FIGS. 8A-B show calcium (Ca2+) signal detection displayed as a dot plot. FIG. 8A: Dump channel+ cells (TCRb+, and CD19+), loaded with 2 μM Fluo-4 before and after addition of Olfr2 agonist octanal (Oct 10 μM), and antagonist Citral (Cit 100 μM) alone or combined (Oct+Cit). Oct, and Cit injected at 60 seconds. Whole aortas were digested, stained with Fluo4 (2 μM) at 37° C. for 30 min, then washed and incubated with cell surface markers at RT for 20 min CD45+, live, dump channel+(TCRb+, and CD19+) cells were analyzed by flow cytometry. FIG. 8B: The time average Median Fluorescence Intensity (MFI) of Fluo-4 is reported. SD is calculated among the cells for each time point (n 20-50). The analysis is made out one of three experiments.

FIGS. 9A-B shows the results of evaluating octanal dose response. Octanal (Oct) dose response analysis on representative pro inflammatory genes (Ccl4 and Nos2). Explanted aortas of Apoe−/− mice kept in WD, were treated for 12h with three Octanal concentrations (3 μM, 10 μM and 30 μM) with (FIG. 9A) and without (FIG. 9B) LPS (500 ng/mL). After incubation whole aortas were transferred into Qiazol (500 μl; Qiagen) and digested with gentleMACS™ Dissociator (Miltenyi). RNA extraction was performed using a Qiazol/RNAeasy micro kit hybrid protocol (Qiagen). Total RNA was quantified using a nanodrop spectrophotometer (Peqlab) and 500 ng were reverse transcribed into cDNA using Omniscript reverse transcriptase (Qiagen). Real time PCR reactions were performed according to the RT²SYBR green gene expression assay protocol (Qiagen). RT2 SYBR Green qPCR master mix and premade RT²qPCR Primer Assays for mouse Ccl2, Ccl4, and Gapdh were used. Relative expression was normalized to Gapdh expression and the untreated control. Data are presented as means±SEM. n=3 per group *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test.

FIGS. 10A-J shows that octanal concentration increases in blood plasma of western diet fed mice and exacerbates atherosclerosis. FIGS. 10A-C: Murine blood plasma was analyzed for octanal by derivatization and stable isotope dilution LC/MS/MS. [²H₁₆]octanal was spiked to plasma before derivatization reaction as internal standard. Male WT C57BL/6J (B) and Apoe^−/− (C) mice were fed chow diet (CD) or western diet (WD) and plasma was analyzed for octanal concentrations (n=9/10/group). FIGS. 10D-G) En face atherosclerosis quantification in vehicle-, octanal- or citral-treated mice. Apoe^−/− mice (n=9-11/group) were fed WD for 8 weeks and injected every three days intraperitoneally with vehicle (PBS+0.1% DMSO), octanal (Oct, 10 mg/kg), or citral (Cit, 10 mg/kg) for the last 4 weeks for a total of 12 injections. D) Representative pictures of pinned aortic arches of vehicle and Oct-treated mice. Scale bar=0.5 cm. E) En face atherosclerotic lesion size evaluation in aortic arches as percentage of total area analyzed. F) Representative pictures of pinned aortic arches of mice vehicle- or Cit-treated mice. Scale bar=0.5 cm. G) Aortic arch lesion size quantification of citral treated mice displayed as percentage of total area analyzed. FIGS. 10H-J) Lldr^−/− male mice (n=8-10/group) were lethally irradiated and reconstituted with Rtp1/Rtp2^+/+, Rtp1/Rtp2^+/−, Rtp1/Rtp2^−/−bone marrow cells and fed high cholesterol diet for 12 weeks. Olfr2 expression of BMDMs from BM transferred mice by (H) western blot or (I) flow cytometry. J) Aortic arch lesion size quantification as percent of analyzed arch area. Data are presented as mean±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, non-parametric Kruskal-Wallis test with Dunn's test for multiple comparisons and unpaired t-test.

FIGS. 11A-B shows body weight and hematological parameters, in octanal (FIG. 11A) and citral (FIG. 11B) treated mice. Neutrophils (NE), Lymphocytes (LY), Monocytes (MO), Eosinophils (EO) and Basophils (BA) % among total withe blood cells is reported.

FIG. 12 shows body weight and hematological parameters, in Lldr−/− male mice (n 8/10 per group) transplanted with Rtp1/Rtp2+/+, Rtp1/Rtp2+/−, Rtp1/Rtp2−/− derived Bone Marrow cells and treated 12 wks with high cholesterol diet. Neutrophils (NE), Lymphocytes (LY), Monocytes (MO), Eosinophils (EO) and Basophils (BA) % among total with blood cells is reported.

FIG. 13 shows that human macrophages express the Olfr2 orthologue OR6A2 and ligation activates a pro-inflammatory response. FIG. 13A) Olfactory receptor and accessory gene expression in human atherosclerotic plaques and PBMCs shown as a heat map (red=high, blue=low, by row). Data was extracted from the BIKE database (GSE21545). Olfactory receptors highly expressed in plaques including OR6A2 (green) are highlighted. FIGS. 13B-E) Monocytes from healthy human donors were differentiated into macrophages (hMDMs). hMDMs were untreated or incubated with octanal (Oct, 10 μM) and LPS, (500 ng/mL) alone or combined (LPS+Oct) for 12 h. Bi) Quantitative real time PCR analysis of OR6A2 expression normalized to Gapdh expression and untreated control. Bii and iii) Flow cytometric analysis of OR6A2 expression on living hMDMs reported as MFI. FIG. 13C) High resolution imaging of hMDMs stained for OR6A2 (AF488) and hoechst dye (nuclei). FIG. 13D) Real time PCR quantification for human IL6, TNF, and NOS2 gene expression normalized to Gapdh and untreated control. FIG. 13E) IL6 and TNF protein quantification by cytokine bead arrays and flow cytometry in supernatants of untreated and stimulated hMDMs (n=4/group). FIG. 13F) hMDMs were treated with LPS (50 ng/mL) for 18 h and left untreated or further incubated with Oct and Cit alone or combined. IL-1β protein in supernatants was quantified by a human cytokine bead array and flow cytometry. FIG. 13G) hMDMs were transfected with a OR6A2 small interfering RNAs (SiORA6A2) or scramble control siRNAs (SiCtrl). After 48 h, hMDMs were treated with LPS (500 ng/mL) alone or with LPS+Oct (10 μM) for 12 h. OR6A2, TNF, IL6 and NOS2 gene expression analysis was analyzed by real time PCR and normalized to Gapdh and LPS siCtrl treated controls. All experiments were replicated at least three times. Data are presented as mean±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test and unpaired t-test.

FIG. 14 shows an analysis of pro inflammatory genes CCL2, CCL4, and Tnf in aortas of Apoe^−/− mice. Explanted aortas of Apoe^−/− mice kept in WD (2 wks), were treated for 12h with LPS (500 ng/mL) and different odorants (10 μM) or left untreated. Relative expression of Ccl2, Ccl4, and Tnf was quantified by real time PCR analysis and normalized to Gapdh expression and untreated control applying the 2-ΔΔCT method. N=3 per group.

FIG. 15 shows a statistical analysis of the relative expression of pro inflammatory genes Ccl2, Ccl4 and Tnf in FIG. 14. Average relative expression for Ccl2, Ccl4, and Tnf was quantified by real time PCR analysis and normalized to Gapdh expression and untreated control applying the 2-ΔΔCT method. N=3 per group. p calculated by unpaired T Test. A p value<0.05 was considered significative.

FIG. 16 shows significantly modulated proteins in plasma from octanal treated mice. EDTA plasma samples were collected from octanal treated and vehicle treated mice at the end of the 8 weeks and were sent for analysis of 92 proteins. Analysis of 92 proteins comprising the Olink Mouse exploratory panel (https://www.olink.com/products/mouse-exploratory/) was performed using PEA (Proximity Extension Assay) technology. The PEA technique allows simultaneous assessment of proteins using oligonucleotide-labeled antibody probe pairs that bind to each protein within the sample. The PEA technique also permits accurate assessment of protein levels with repeated measurements by requiring both dual recognition of correctly matched antibody pairs and DNA-barcoding from sequence-specific oligonucleotides to generate a signal (PLoS ONE. 2014; 9(4)). The assay measures fold change in log 2 units. For this analysis, the raw data are converted into a t-statistic which can be compared across assays. Data are presented as means±SEM. P value<0.05 calculated by unpaired t-test.

FIG. 17 shows significantly modulated proteins in plasma from citral treated mice. EDTA plasma samples were collected from citral treated and vehicle treated mice at the end of the 8 weeks and were sent for analysis of 92 proteins. Analysis of 92 proteins comprising the Olink Mouse exploratory panel (https://www.olink.com/products/mouse-exploratory/) was performed using PEA (Proximity Extension Assay) technology, discussed above. Data are presented as means±SEM. P value<0.05. p calculated by unpaired t-test.

FIG. 18 shows “germ free” (no microbiome) (GF) and conventional C57BL/6J (Ctrl) mice plasma analysed for octanal concentrations (n=5/group).

DETAILED DESCRIPTION

In the present invention, a number of olfactory receptors (Olfrs), as well as the essential Olfr accessory transport proteins RTP1 (Receptor Transporter Protein 1) and RTP2 (Receptor Transporter Protein 2), are shown to be expressed in vascular macrophages isolated from ApoE−/− murine aortas. Furthermore, stimulation of the olfactory receptor Olfr2 by a small molecule odorant (octanal) induces expression of inflammatory mediators, CCL2 (C-C motif chemokine ligand 2), iNOS (inducible Nitric Oxide Synthase) and TNF (tumor necrosis factor alpha); exposure to both octanal and LPS (lipopolysaccharide) exacerbate the inflammatory response, indicating that the inflammation may be caused by microbiota-derived odorants.

Olfactory receptors (Olfrs) are class A, G protein coupled receptors (GPCRs) that are bound by volatile chemical ligands, or odorants. Olfrs were first described in olfactory epithelial cells in the nasal cavity of rats^1,2. Olfrs have an average length of 320±25 amino acid residues and share characteristic conserved motifs³. Olfr genes constitute the largest family GPCRs with ˜1100 genes in mice and ˜400 in humans^4,5. Many Olfrs require the transporters Rtp1 and 2 and other molecules such as receptor expression enhancing protein 3 (Reep3) for expression⁶. Olfrs couple through a specialized G protein (Gαolf, Gnal)⁷to adenylate cyclase 3 (Acy3)^8-111. Activation of Gα(olf) and Acy3 induces an increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) followed by the activation of cAMP-gated channels, influx of extracellular Na⁺ and Ca²⁺, and membrane depolarization.

Applicants have discovered that the Olfr2 ligand octanal significantly enhances LPS-induced inflammatory cytokines, which is blocked by the Olfr2 antagonist citral. Octanal naturally occurred in citrus oils and is used as a flavor food additive. It is in a class of odorants (aldheydes) that may have effects on atherosclerosis. Treating Apoe−/− mice with citral reduced their atherosclerotic lesions by ˜50%. Olfr2 is highly expressed in vascular macrophage. qRT-PCR showed that Olfr2 expression is increased fourfold by LPS and further increased by adding its ligand octanal, but octanal alone had no effect on Olfr2 expression. This increased expression of Olfr2 was confirmed at the protein level. Without being bound by theory, Applicants believe that it may be caused by increased expression of the transporters Rpt 1 and 2, which are both induced by LPS. LPS treatment of mice also increased Olfr2 expression on Ly6C+ blood monocytes and, to a lesser extent, on Ly6C-patrolling monocytes, but not on any other immune cells in the aorta or in blood (data not shown).

To begin to address the possible function of Olfr2 in vascular macrophages, inflammatory cytokines, chemokines and the M1-defining enzyme iNOS were surveyed by qRT-PCR. The known induction by LPS of CCL2 (=MCP-1) and CCL4 was significantly enhanced by octanal, and even octanal alone (without LPS) resulted in a measurable increase of both chemokines. iNOS expression induced by LPS was greatly enhanced by octanal. Octanal had the greatest effect on TNF, where ligation of Olfr2 was required to reveal an LPS-induced increase. The enhanced production of CCL2, CCL4 and TNF was confirmed at the protein level by cytometric bead array. Octanal also boosted the expression of TNF in both Ly6C+ and Ly6C− blood monocytes.

Some microbiota-derived molecules are known to promote atherosclerosis, e.g., TMAO. TMAO is produced by intestinal bacteria from choline. It has various effects, including enhanced platelet activation. Other microbiota-derived odorants have been identified. By way of example, and not by way of limitation, some of the identified microbiota-derived odorants include TMA and its liver derivative TMAO, p-cresol and its liver derivatives p-cresol-sulfate and p-cresol-glucuronide, indole and its liver derivatives indoxyl-sulfate and indoxyl-glucuronide, tryptamine, serotonin (also endogenous), SCFA (acetic, propionic, butyric, valeric, isovaleric, succinic, lactic acid), Phenylacetic acid and its liver derivatives phenylacetyl-glutamine and phenylacetyl-glycine, Indole-acetic acid, Indole-propionic acid, Phenyl-acetic acid, Phenyl-propionic acid, Benzoic acid and its liver derivative hippuric acid (also 2-hydroxy benzoic, 3-hydroxy benzoic and 4-hydroxybenzoic and their liver derivatives).

Thus, in certain embodiments, the olfactory receptors identified herein are modulated for treatment of an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an autoimmune response, disorder or disease including but not limited to rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

In certain embodiments, the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an autoimmune response, disorder or disease is a symptom, side-effect or result of is of cancer or a pathogen infection.

In other embodiments, the olfactory receptors identified herein are modulated for treatment of a neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy.

In some embodiment, the present invention comprises modulating one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIGS. 2A and 2B. In certain embodiments, the present invention comprises decreasing, reducing, inhibiting, suppressing, limiting or controlling expression or activity of one or more olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIGS. 2A and 2B. In other embodiments, the present invention comprises enhancing, stimulating, inducing or increasing expression or activity of one or more olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIGS. 2A and 2B. In certain embodiments, the present invention comprises a combination of decreasing, reducing, inhibiting, suppressing, limiting or controlling expression or activity of one or olfactory receptors listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIGS. 2A and 2B, and enhancing, stimulating, inducing or increasing expression or activity of one or more different olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIGS. 2A and 2B.

Non-limiting examples of an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an autoimmune response, disorder or disease include rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

Non-limiting examples of neoplasia, neoplastic disorders, tumors, cancers or malignancies treated by the present methods include, a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma as well as a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.

Disclosed herein are methods of modulating an immune response in a subject in need thereof. In some embodiments, the method of modulating an immune response in a subject, comprises modulating expression or activity of one or more olfactory receptors (OLFR). The OLFR may be expressed by a cell in vivo. The cell may be an animal cell, with the proviso that the cell is not an olfactory cell. The cell may be a macrophage. The macrophage may be a vascular macrophage.

The modulation may comprise one or more of inhibiting, decreasing, reducing, suppressing, limiting or controlling the immune response by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the (OLFR). The modulation may comprise one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the (OLFR). The modulation may comprise one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the (OLFR). The modulation may comprise one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, or an adverse symptom of the autoimmune response, disorder or disease in the subject.

The methods or uses disclosed herein may comprise modulating an adverse symptom. The adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an adverse symptom of the autoimmune response, disorder or disease may be swelling, pain, rash, headache, fever, nausea, diarrhea, bloat, lethargy, skeletal joint stiffness or tissue or cell damage. The adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or the adverse symptom of the autoimmune response, disorder or disease may be chronic or acute.

The immune disorder, inflammatory response, inflammation, autoimmune response disorder or autoimmune disease may comprise rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

The modulation may comprise one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse cardiovascular event or cardiovascular disease by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR. The adverse cardiovascular event or cardiovascular disease may comprise coronary artery disease, peripheral artery disease, cerebrovascular disease, renal artery disease, stroke, myocardial infarction (heart attack), ischemic heart failure, transient ischemic attack or brain trauma, atherosclerosis, atherosclerotic plaque formation or elevated blood cholesterol.

The modulation may comprise one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling atherosclerosis, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.

The method may comprise one or more of reducing or inhibiting in a subject viral, bacterial or fungal infection or a neoplasia, neoplastic disorder, tumor, cancer or malignancy, by a method comprising administering to the subject an effective amount of an agent that increases the expression of or activates the OLFR.

The modulation may comprise one or more of comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, or viral, bacterial or fungal infection by a method comprising administering to the subject an effective amount of an agent that modulates the expression of or activity of the OLFR.

The OLFR may be enhanced or stimulated in the subject by administration of an effective amount of an agent that stimulates or enhances the activity of the OLFR. The OLFR may be enhanced or stimulated in the subject by administration of an OLFR. The OLFR may be enhanced or stimulated in the subject by administration of a nucleotide that encodes an OLFR. The OLFR may be enhanced or stimulated in the subject by administration of an OLFR ligand. The OLFR may be enhanced or stimulated in the subject by administration of a receptor transporting protein 1 (RTP1) or a nucleotide encoding RTP1. The OLFR may be enhanced or stimulated in the subject by administration of a RTP2 or a nucleotide encoding RTP2. The OLFR may be enhanced or stimulated in the subject by administration of a receptor expression enhancing protein 1 (REEP1) or a nucleotide encoding REEP1. The OLFR may be enhanced or stimulated in the subject by administration of an aminoacylase 3 (Acy3) or a nucleotide encoding Acy3. The OLFR may be enhanced or stimulated in the subject by administration of a guanine nucleotide-binding protein G(olf) subunit alpha (Gnal) or a nucleotide encoding Gnal.

The methods disclosed herein may be used to treat a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Further disclosed herein is the use of an agent that modulates the activity or expression of an OLFR in the preparation of a medicament for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Further disclosed herein is the use of an agent that increases the activity or expression of an OLFR in the preparation of a medicament for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Further disclosed herein is the use of an OLFR ligand in the preparation of a medicament for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Disclosed herein is the use of octanal in the preparation of a medicament for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Disclosed herein is the use of an OLFR ligand for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy. Further disclosed herein is the use of octanal for the treatment of a neoplasia, neoplastic disorder, tumor, cancer or malignancy.

The neoplasia, neoplastic disorder, tumor, cancer or malignancy treated may be a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma; or a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.

The methods and uses disclosed herein may comprise modulating the activity or expression of an OLFR. The OLFR may be an OLFR listed in any one of Tables 1-9 Tables 2A and 2B. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2.

The agent may be selected from the group of: a ligand or small molecule that binds to the OLFR or blocks the binding of the OLFR to the ligand or an agent that inhibits the expression of the OLFR by the cell. The agent may be a ligand or small molecule that binds to the OLFR. The agent may be a ligand or small molecule that blocks the binding of the OLFR to the ligand. The agent may inhibit the expression of the OLFR by the cell. The agent may be selected from the group of an antibody, fragment or mimetic that binds to OLFR or an OLFR ligand, an anti-OLFR gene silencing agent, or octanal or a prodrug or solvate thereof. The agent may be an antibody, fragment or mimetic that binds to OLFR. The agent may be an antibody, fragment or mimetic that binds to an OLFR ligand. The agent may be an anti-OLFR gene silencing agent. The agent may be octanal, heptanal, or a prodrug or solvate thereof.

The agent may activate the OLFR by increasing the trafficking of the OLFR to a plasma membrane of a cell. The agent may be a protein selected from the group of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), or guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

The agent may be a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

The immune response may be stimulated by a method comprising administering an agent that increases expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), interleukin 1-beta (IL-1B), interleukin 18 (IL-18), and nitric oxide synthase 2 (NOS2). The inflammatory cytokine may be TNF. The inflammatory cytokine may be CCL2. The inflammatory cytokine may be CCL4. The inflammatory cytokine may be CCL5. The inflammatory cytokine may be IL-6. The inflammatory cytokine may be IL-1B. The inflammatory cytokine may be IL-18. The inflammatory cytokine may be NOS2.

Increasing or Stimulating an Immune Response

Disclosed herein are methods of increasing or stimulating an immune response in a subject in need thereof. In some embodiments, the method comprises administering to the subject an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that increases the expression of or activity of an olfactory receptor (OLFR), thereby increasing or stimulating an immune response in the subject. In some embodiments, the method comprises administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby increasing an immune response in the subject. Further disclosed herein is the use of an olfactory receptor (OLFR) in the manufacture of a medicament for increasing or stimulating an immune response. Disclosed herein is the use of an agent that increases the expression of or activity of an olfactory receptor (OLFR) in the manufacture of a medicament for increasing or stimulating an immune response. Disclosed herein is the use of an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell in the manufacture of a medicament for increasing or stimulating an immune response. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a ligand that binds to the OLFR. The agent may be an OLFR agonist. The agonist may be selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal, 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, decyl aldehyde. the agonist may be selected from the list of agonists provided in Table 8. The agent may be octanal, heptanal, or a prodrug or solvate thereof. The agent may activate the OLFR by increasing the trafficking of the OLFR to a plasma membrane of a cell. The agent may be a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). The agent may comprise a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). Stimulating an immune response may comprise increasing expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2).

In some embodiments, the immune response is increased or stimulated by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, or 100% as compared to the immune response in a subject who is not treated with the agent. The immune response may be increased or stimulated by at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more as compared to the immune response in a subject who is not treated with the agent. The immune response may be increased or stimulated by at least 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100-fold or more as compared to the immune response in a subject who is not treated with the agent. The immune response may be measured by detecting the level of one or more inflammatory cytokines. Alternatively, or additionally, the immune response is measured by detecting the expression of one or more inflammatory cytokines. In some embodiments, the immune response is measured by detecting one or more circulating cytokines and/or chemokines. In some embodiments, the immune response is measured by detecting one or more cells selected from activated CD8 T cells, Th1 cells, Th2 cells, Th17 cells, TFH cells, TIP-DCs, and M1 polarized macrophages. In some embodiments, the immune response is measured by detecting one or more markers of T cell activation. In some embodiments, the immune response is measured by detecting the levels of antibody titers to one or more tumor antigens. In some embodiments, an increase in the expression level of or more inflammatory cytokines is indicative of an increase in the immune response. In some embodiments, an increase in the quantity of circulating cytokines and/or chemokines is indicative of an increase in the immune response. In some embodiments, an increase in the quantity of one or more cells is indicative of an increase in the immune response. In some embodiments, an increase in quantity of one or more markers of T cell activation that is detected is indicative of an increase in the immune response. In some embodiments, an increase in the level of antibody titers detected is indicative of an increase in the immune response. Alternatively, or additionally, the immune response is measured by a method such as ELISA, cytometric bead array, Olink proteomic, and flow cytometry.

Suppressing an Immune Response

Disclosed herein are methods of suppressing an immune response in a subject in need thereof. In some embodiments, the method comprises administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR), thereby suppressing an immune response in the subject. In some embodiments, the method comprises administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby suppressing an immune response in the subject. Further disclosed herein are uses of an agent that decreases the expression or activity of an OLFR in the manufacture of a medicament for suppressing an immune response. Further disclosed herein is the use of an agent that inhibits the trafficking of an OLFR to a plasma membrane of a cell in the manufacture of a medicament for suppressing an immune response. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a gene silencing agent. The gene silencing agent may be selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. The RNAi molecule may be selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). The agent may decrease the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. The agent may be an OLFR antagonist. The OLFR antagonist may be citral, a solvate or prodrug thereof. The OLFR antagonist may be methylcinnamaldehyde, hydrocinnamaldehyde, bourgeonal, undecanal, methyl isoeugenol a solvate or prodrug thereof. The antagonist may be selected from the list of antagonists provided in Table 8, or a solvate or prodrug thereof. The agent may decrease the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell. The agent may be an antibody, fragment or mimetic thereof that binds to an OLFR.

In some embodiments, the immune response is suppressed or decreased by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, or 100% as compared to the immune response in a subject who is not treated with the agent. The immune response may be suppressed or decreased by at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more as compared to the immune response in a subject who is not treated with the agent. The immune response may be suppressed or decreased by at least 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100-fold or more as compared to the immune response in a subject who is not treated with the agent. The immune response may be measured by detecting the level of one or more inflammatory cytokines. Alternatively, or additionally, the immune response is measured by detecting the expression of one or more inflammatory cytokines. In some embodiments, the immune response is measured by detecting one or more circulating cytokines and/or chemokines. In some embodiments, the immune response is measured by detecting one or more cells selected from activated CD8 T cells, Th1 cells, Th2 cells, Th17 cells, TFH cells, TIP-DCs, and M1 polarized macrophages. In some embodiments, the immune response is measured by detecting one or more markers of T cell activation. In some embodiments, the immune response is measured by detecting the levels of antibody titers to one or more tumor antigens. In some embodiments, a decrease in the expression level of or more inflammatory cytokines is indicative of a decrease or suppression in the immune response. In some embodiments, a decrease in the quantity of circulating cytokines and/or chemokines is indicative of a decrease or suppression in the immune response. In some embodiments, a decrease in the quantity of one or more cells is indicative of a decrease or suppression in the immune response. In some embodiments, a decrease in quantity of one or more markers of T cell activation that is detected is indicative of a decrease or suppression in the immune response. In some embodiments, a decrease in the level of antibody titers detected is indicative of a decrease or suppression in the immune response. Alternatively, or additionally, the immune response is measured by a method such as ELISA, cytometric bead array, Olink proteomic, and flow cytometry.

Autoimmune Disease

Further disclosed herein are methods of treating an autoimmune disease in a subject in need thereof. In some embodiments, the method comprises administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR). Alternatively, or additionally, the method of treating an autoimmune disease in a subject in need thereof, comprises administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. Further disclosed herein is the use of an agent that decreases the expression of or activity of an olfactory receptor (OLFR) in the manufacture of a medicament for treating an autoimmune disease. Also disclosed herein is the use of an agent that decreases the expression of or activity of an olfactory receptor (OLFR) for the treatment of an autoimmune disease. Further disclosed herein is the use of an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell in the manufacture of a medicament for treating an autoimmune disease. Also disclosed herein is the use of an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell for the treatment of an autoimmune disease. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a gene silencing agent. The gene silencing agent may be selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. The RNAi molecule may be selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). The agent may decrease the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. The agent may be an OLFR antagonist. The OLFR antagonist may be citral, a solvate or prodrug thereof. The OLFR antagonist may be methylcinnamaldehyde, hydrocinnamaldehyde, bourgeonal, undecanal, methyl isoeugenol a solvate or prodrug thereof. The antagonist may be selected from the list of antagonists provided in Table 9, or a solvate or prodrug thereof.

The agent may decrease the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell. The agent may be an antibody, fragment or mimetic thereof that binds to an OLFR.

In some embodiments, the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.

Cardiovascular Disease

Disclosed herein are methods of treating a cardiovascular disease in a subject in need thereof. In some embodiments, the method comprises administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. Further disclosed herein is the use of an agent that decreases the expression of or activity of an olfactory receptor (OLFR) in the manufacture of a medicament for treating a cardiovascular disease. Also disclosed herein is the use of an agent that decreases the expression of or activity of an olfactory receptor (OLFR) for the treatment of a cardiovascular disease. Further disclosed herein is the use of an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell in the manufacture of a medicament for treating a cardiovascular disease. Also disclosed herein is the use of an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell for the treatment of a cardiovascular disease. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a gene silencing agent. The gene silencing agent may be selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. The RNAi molecule may be selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). The agent may decrease the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. The agent may be an OLFR antagonist. The OLFR antagonist may be citral, a solvate or prodrug thereof. The OLFR antagonist may be methylcinnamaldehyde, hydrocinnamaldehyde, bourgeonal, undecanal, methyl isoeugenol a solvate or prodrug thereof. The antagonist may be selected from the list of antagonists provided in Table 9 or a solvate or prodrug thereof. The agent may decrease the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell. The agent may be an antibody, fragment or mimetic thereof that binds to an OLFR.

In some embodiments, the adverse cardiovascular event or cardiovascular disease is selected from the group consisting of coronary artery disease, peripheral artery disease, cerebrovascular disease, renal artery disease, stroke, myocardial infarction (heart attack), ischemic heart failure, transient ischemic attack or brain trauma, atherosclerosis, atherosclerotic plaque formation and elevated blood cholesterol.

Infections or Infectious Diseases

Disclosed herein are methods of treating an infection or infectious disease in a subject in need thereof. In some embodiments, the method comprises administering to the subject an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. Further disclosed herein is the use of an olfactory receptor (OLFR) in the manufacture of a medicament for the treatment of an infection. Further disclosed herein is the use of an agent that increases the expression of or activates an olfactory receptor (OLFR) in the manufacture of a medicament for the treatment of an infection. Disclosed herein is the use of an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell in the manufacture of a medicament for the treatment of an infection. Disclosed herein is the use of an olfactory receptor (OLFR) for the treatment of an infection or infectious disease. Disclosed herein is the use of an agent that increases the expression of or activates an olfactory receptor (OLFR) for the treatment of an infection or infectious disease. Disclosed herein is the use of an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell for the treatment of an infection or infectious disease. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a ligand that binds to the OLFR. The agent may be an OLFR agonist. The agonist may be selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal, 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, and decyl aldehyde. The agonist may be selected from the list of agonists provided in Table 8. The agent may be octanal, heptanal, or a prodrug or solvate thereof. The agent may activate the OLFR by increasing the trafficking of the OLFR to a plasma membrane of a cell. The agent may be a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). The agent may comprise a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). Stimulating an immune response may comprise increasing expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2). The infection may be a viral infection. The infection may be a bacterial infection. The infection may be a fungal infection.

In some embodiments, the infection is a viral infection. In some embodiments, the viral infection is caused by a virus selected from the group consisting of influenza virus, enterovirus (such as coxsackievirus and echovirus), cytomegalovirus, Zika virus, rabies virus, West Nile virus, rubella virus, polio virus, rotavirus, norovirus, herpes simplex virus, varicella-zoster virus, lymphocytic choriomeningitis virus, human immunodeficiency virus, Chikungunya virus, Crimean-Congo hemorrhagic fever virus, Japanese encephalitis virus, Rift Valley Fever virus, Ross River virus, and louping ill virus.

In some embodiments, the infection is a bacterial infection. In some embodiments, the bacterial infection is caused by a bacteria selected from the group consisting of streptococcus, staphylococcus, Escherichia coli, Campylobacter jejuni, Clostridium botulinum, Listeria monocytogenes, salmonella, and vibrio.

In some embodiments, the infection is a fungal infection. In some embodiments, the fungal infection is caused by a fungus selected from the group consisting aspergillus, candida, coccidioides, sphorotrichosis, Pneumocystis jirovecii, Blastomyces, Histoplasma, Cryptococcus neoformans, and Talaromyces. Examples of fungal infections include, but are not limited to aspergillosis, candidiasis, C. gattii infection, fungal nail infection, mucormycosis, pneumocystis pneumonia, blastomycosis, sporotrichosis, histoplasmosis, mycetoma, ringworm, talaromycosis, athlete's foot and yeast infection.

In some embodiments, the infection is selected from the group consisting of a respiratory infection, gastrointestinal infection, liver infection, nervous system infection, ear infection, throat infection, bladder infection, kidney infection, urinary tract infection, sexually transmitted diseases, and skin infection.

In some embodiments, the infection is a respiratory infection. Examples of respiratory infections include, but are not limited to, sore throat, bronchitis, sinusitis, tuberculosis, and pneumonia.

In some embodiments, the infection is a sexually transmitted disease. Examples of sexually transmitted diseases include, but are not limited to, chlamydia, gonorrhea, syphilis, and bacterial vaginosis.

In some embodiments, the infection is a skin infection. Examples of skin infections include, but are not limited to, cellulitis, folliculitis, impetigo, and boils.

Cancer

Disclosed herein are methods of treating cancer in a subject in need thereof. In some embodiments, the method comprises administering to the subject an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR). Alternatively, or additionally, the method comprises administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. Further disclosed herein is the use of an agent that increases the expression of or activates an olfactory receptor (OLFR) in the manufacture of a medicament for the treatment of cancer. Disclosed herein is the use of an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell in the manufacture of a medicament for the treatment of cancer. Disclosed herein is the use of an agent that increases the expression of or activates an olfactory receptor (OLFR) for the treatment of cancer. Disclosed herein is the use of an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell for the treatment of cancer. The OLFR may be an OLFR listed in Table 1. The OLFR may be an OLFR listed in Table 2. The OLFR may be an OLFR listed in Table 3. The OLFR may be an OLFR listed in Table 4. The OLFR may be an OLFR listed in Table 5. The OLFR may be an OLFR listed in Table 6. The OLFR may be an OLFR listed in Table 7. The OLFR may be an OLFR listed in Table 8. The OLFR may be an OLFR listed in Table 9. The OLFR may be an OLFR listed in FIG. 2A. The OLFR may be an OLFR listed in FIG. 2B. The OLFR may be selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The OLFR may be OR7C1. The OLFR may be OR7D4. The OLFR may be OR10A6. The OLFR may be OR11H6. The OLFR may be OR4E2. The OLFR may be OR10H1. The OLFR may be OR6A2. The agent may be a ligand that binds to the OLFR. The agent may be an OLFR agonist. The agonist may be selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal, 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, and decyl aldehyde. The agonist may be selected from the list of agonists provided in Table 8. The agent may be octanal, heptanal, or a prodrug or solvate thereof. The agent may activate the OLFR by increasing the trafficking of the OLFR to a plasma membrane of a cell. The agent may be a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). The agent may comprise a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). Stimulating an immune response may comprise increasing expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5 interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2). The administration may be local. The administration may be systemic. The administration may comprise an intravenous method. The subject may be a mammal. The subject may have or may be predisposed to a disease or disorder involving an immune dysregulation. The subject may be a human patient.

In some embodiments, the neoplasia, neoplastic disorder, tumor, cancer or malignancy treated is selected from the group consisting of a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma; or a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.

Agents

An “agent” as used herein refers to any molecule (e.g. antibody, Fab fragment, protein, peptide, nucleic acid, synthetic chemical, small chemical molecule, ligand mimetic) that can be administered to a subject. An agent that modulates expression or activity of an olfactory receptor provided in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIG. 2A, and FIG. 2B is a molecule or composition that when administered to a subject modulates expression or activity of an olfactory receptor provided in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIG. 2A, and FIG. 2B. In certain embodiments, the agent modulates, inhibits, blocks, decreases, increases, enhances, promotes or elicits expression or activity of an olfactory receptor provided in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIG. 2A, and FIG. 2B. In some embodiments, the agent modulates, enhances, stimulates, induces or increases expression or activity of an olfactory receptor provided in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIG. 2A, and FIG. 2B. In certain embodiments, the agent modulates, inhibits, blocks, decreases, increases, enhances, promotes or elicits an immune response. In some embodiments, the agent modulates, enhances, stimulates, induces or increases an immune response. In certain embodiments, modulation of an immune response includes modulating the innate immune response (e.g. endothelial cells, macrophages, monocytes, dendritic cells, cytokines).

The methods, uses, and kits disclosed herein may comprise one or more agents that modulate the activity of an olfactory receptor (OLFR). The agent may be selected from the group of: a ligand or small molecule that binds to the OLFR or blocks the binding of the OLFR to the ligand or an agent that inhibits the expression of the OLFR by the cell. The agent may be selected from the group of an antibody, fragment or mimetic that binds to OLFR or an OLFR ligand, an anti-OLFR gene silencing agent, or octanal or a prodrug or solvate thereof.

The methods, uses, and kits disclosed herein may comprise one or more agents that increase the expression of or activity of an OLFR. The agent may be a ligand that binds to an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B. The agent may be a ligand that binds to an OLFR listed in Table 7. The agent may be a ligand that binds to an OLFR selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The agent may be octanal, heptanal, or a prodrug or solvate thereof. In some embodiments, the expression of the OLFR is increased by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% or more. In some embodiments, the expression of the OLFR is increased by at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more. In some embodiments, the activity of the OLFR is increased by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% or more. In some embodiments, the activity of the OLFR is increased by at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more. In some embodiments, the activity of the OLFR is determined by measuring the level of expression of one or more inflammatory cytokines. In some embodiments, the activity of the OLFR is determined by measuring the level of secretion of one or more inflammatory cytokines. In some embodiments, the increase in the expression of OLFR is based on a comparison to the subject who has not been administered the agent. Alternatively, or additionally, the expression of the OLFR is measured over a time period and the increase in the level of expression of the OLFR is based on a comparison of samples from the subject over two or more time points. In some embodiments, the increase in the activity of OLFR is based on a comparison to the subject who has not been administered the agent. Alternatively, or additionally, the activity of the OLFR is measured over a time period and the increase in the activity of the OLFR is based on a comparison of samples from the subject over two or more time points.

The methods, uses, and kits disclosed herein may comprise one or more agents that increase or promote the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. The agent may be a protein selected from the group of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), or guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). The agent may comprise a nucleotide encoding a protein selected from the group of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), or guanine nucleotide-binding protein G(olf) subunit alpha (Gnal). In some embodiments, the level of trafficking of the OLFR to the plasma membrane is increased by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% or more. In some embodiments, the level of trafficking of the OLFR to the plasma membrane is increased by at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more. In some embodiments, the level of trafficking of the OLFR to the plasma membrane is determined by detecting the amount of OLFR on the surface of the cell. In some embodiments, the increase in the level of trafficking of the OLFR to the plasma membrane is based on a comparison to the subject who has not been administered the agent. Alternatively, or additionally, the level of trafficking of the OLFR to the plasma membrane is measured over a time period and the increase in the level of trafficking is based on a comparison of samples from the subject over two or more time points.

The methods, uses, and kits disclosed herein may comprise one or more agents that increase expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2).

The methods, uses, and kits disclosed herein may comprise one or more agents that decrease or inhibit the expression of or activity of an OLFR. The agent may be a gene silencing agent. The gene silencing agent may be selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme. The RNAi molecule may be selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). The gene silencing agent may target an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B. The gene silencing agent may target an OLFR listed in Table 7. The gene silencing agent may target an OLFR selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. In some embodiments, the expression of the OLFR is decreased by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% or more. In some embodiments, the expression of the OLFR is decreased by at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more. In some embodiments, the activity of the OLFR is decreased by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% or more. In some embodiments, the activity of the OLFR is decreased by at least about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10-fold or more. In some embodiments, the activity of the OLFR is determined by measuring the level of expression of one or more inflammatory cytokines. In some embodiments, the activity of the OLFR is determined by measuring the level of secretion of one or more inflammatory cytokines. In some embodiments, the decrease in the expression of OLFR is based on a comparison to the subject who has not been administered the agent. Alternatively, or additionally, the expression of the OLFR is measured over a time period and the decrease in the level of expression of the OLFR is based on a comparison of samples from the subject over two or more time points. In some embodiments, the decrease in the activity of OLFR is based on a comparison to the subject who has not been administered the agent. Alternatively, or additionally, the activity of the OLFR is measured over a time period and the decrease in the activity of the OLFR is based on a comparison of samples from the subject over two or more time points.

One of skill in the art can use methods such as RNA interference (RNAi), CRISPR, TALEN, ZFN or other methods that target specific sequences to reduce or eliminate expression and/or function of proteins, such as an OLFR, OLFR ligand, or a protein involved in trafficking of OLFR to the plasma membrane of a cell. CRISPR, TALEN, ZFN or other genome editing tools can also be used to modulate expression and/or function of genes.

As used herein, “RNAi” (RNA interference) refers to the method of reducing or eliminating gene expression in a cell by targeting specific mRNA sequences for degradation via introduction of short pieces of double stranded RNA (dsRNA) and small interfering RNA (such as siRNA, shRNA or miRNA etc.) (Agrawal, N. et al.; Microbiol Mol Biol Rev. 2003; 67:657-685, Arenz, C. et al.; Naturwissenschaften. 2003; 90:345-359, Hannon G J.; Nature. 2002; 418:244-251).

As used herein, the term “CRISPR” refers to a technique of sequence specific genetic manipulation relying on the clustered regularly interspaced short palindromic repeats pathway. CRISPR can be used to perform gene editing and/or gene regulation, as well as to simply target proteins to a specific genomic location. “Gene editing” refers to a type of genetic engineering in which the nucleotide sequence of a target polynucleotide is changed through introduction of deletions, insertions, single stranded or double stranded breaks, or base substitutions to the polynucleotide sequence. In some aspects, CRISPR-mediated gene editing utilizes the pathways of non-homologous end-joining (NHEJ) or homologous recombination to perform the edits. Gene regulation refers to increasing or decreasing the production of specific gene products such as protein or RNA.

The term “gRNA” or “guide RNA” as used herein refers to guide RNA sequences used to target specific polynucleotide sequences for gene editing employing the CRISPR technique. Techniques of designing gRNAs and donor therapeutic polynucleotides for target specificity are well known in the art. For example, Doench, J., et al. Nature biotechnology 2014; 32(12):1262-7, Mohr, S. et al. (2016) FEBS Journal 283: 3232-38, and Graham, D., et al. Genome Biol. 2015; 16: 260. gRNA comprises or alternatively consists essentially of, or yet further consists of a fusion polynucleotide comprising CRISPR RNA (crRNA) and trans-activating CRIPSPR RNA (tracrRNA); or a polynucleotide comprising CRISPR RNA (crRNA) and trans-activating CRIPSPR RNA (tracrRNA). In some aspects, a gRNA is synthetic (Kelley, M. et al. (2016) J of Biotechnology 233 (2016) 74-83).

The term “Cas9” refers to a CRISPR associated endonuclease referred to by this name Non-limiting exemplary Cas9s include Staphylococcus aureus Cas9, nuclease dead Cas9, and orthologs and biological equivalents each thereof. Orthologs include but are not limited to Streptococcus pyogenes Cas9 (“spCas9”), Cas9 from Streptococcus thermophiles, Legionella pneumophilia, Neisseria lactamica, Neisseria meningitides, Francisella novicida; and Cpf1 (which performs cutting functions analogous to Cas9) from various bacterial species including Acidaminococcus spp. and Francisella novicida U112.

As used herein, “TALEN” (transcription activator-like effector nucleases) refers to engineered nucleases that comprise a non-specific DNA-cleaving nuclease fused to a TALE DNA-binding domain, which can target DNA sequences and be used for genome editing. Boch (2011) Nature Biotech. 29: 135-6; and Boch et al. (2009) Science 326: 1509-12; Moscou et al. (2009) Science 326: 3501. TALEs are proteins secreted by Xanthomonas bacteria. The DNA binding domain contains a repeated, highly conserved 33-34 amino acid sequence, with the exception of the 12th and 13th amino acids. These two positions are highly variable, showing a strong correlation with specific nucleotide recognition. They can thus be engineered to bind to a desired DNA sequence. To produce a TALEN, a TALE protein is fused to a nuclease (N), which is a wild-type or mutated Fold endonuclease. Several mutations to Fold have been made for its use in TALENs; these, for example, improve cleavage specificity or activity. Cermak et al. (2011) Nucl. Acids Res. 39: e82; Miller et al. (2011) Nature Biotech. 29: 143-8; Hockemeyer et al. (2011) Nature Biotech. 29: 731-734; Wood et al. (2011) Science 333: 307; Doyon et al. (2010) Nature Methods 8: 74-79; Szczepek et al. (2007) Nature Biotech. 25: 786-793; and Guo et al. (2010) J. Mol. Bio. 200: 96. The Fold domain functions as a dimer, requiring two constructs with unique DNA binding domains for sites in the target genome with proper orientation and spacing. Both the number of amino acid residues between the TALE DNA binding domain and the Fold cleavage domain and the number of bases between the two individual TALEN binding sites appear to be important parameters for achieving high levels of activity. Miller et al. (2011) Nature Biotech. 29: 143-8. TALENs specific to sequences in immune cells can be constructed using any method known in the art, including various schemes using modular components. Zhang et al. (2011) Nature Biotech. 29: 149-53; Geibler et al. (2011) PLoS ONE 6: e19509.

As used herein, “ZFN” (Zinc Finger Nuclease) refers to engineered nucleases that comprise a non-specific DNA-cleaving nuclease fused to a zinc finger DNA binding domain, which can target DNA sequences and be used for genome editing. Like a TALEN, a ZFN comprises a Fold nuclease domain (or derivative thereof) fused to a DNA-binding domain. In the case of a ZFN, the DNA-binding domain comprises one or more zinc fingers. Carroll et al. (2011) Genetics Society of America 188: 773-782; and Kim et al. (1996) Proc. Natl. Acad. Sci. USA 93: 1156-1160. A zinc finger is a small protein structural motif stabilized by one or more zinc ions. A zinc finger can comprise, for example, Cys2His2, and can recognize an approximately 3-bp sequence. Various zinc fingers of known specificity can be combined to produce multi-finger polypeptides which recognize about 6, 9, 12, 15 or 18-bp sequences. Various selection and modular assembly techniques are available to generate zinc fingers (and combinations thereof) recognizing specific sequences, including phage display, yeast one-hybrid systems, bacterial one-hybrid and two-hybrid systems, and mammalian cells. Like a TALEN, a ZFN must dimerize to cleave DNA. Thus, a pair of ZFNs are required to target non-palindromic DNA sites. The two individual ZFNs must bind opposite strands of the DNA with their nucleases properly spaced apart. Bitinaite et al. (1998) Proc. Natl. Acad. Sci. USA 95: 10570-5. ZFNs specific to sequences in immune cells can be constructed using any method known in the art. See, e.g., Provasi (2011) Nature Med. 18: 807-815; Torikai (2013) Blood 122: 1341-1349; Cathomen et al. (2008) Mol. Ther. 16: 1200-7; Guo et al. (2010) J. Mol. Bioi. 400: 96; U.S. Patent Publication 201110158957; and U.S. Patent Publication 2012/0060230.

The agent may decrease the activity of the OLFR by inhibiting the binding of the OLFR with its ligand. The agent may be an OLFR antagonist. The OLFR antagonist may be citral, a solvate or prodrug thereof. The OLFR antagonist may be methylcinnamaldehyde, hydrocinnamaldehyde, bourgeonal, undecanal, methyl isoeugenol a solvate or prodrug thereof. The antagonist may be selected from the list of antagonists provided in Table 9 or a solvate or prodrug thereof.

The agent may decrease the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell. The methods, uses, and kits disclosed herein may comprise one or more agents that decrease or inhibit the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell. The agent may be a gene silencing agent that inhibits the expression of a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

The agent may be an antibody, fragment, derivative, or mimetic thereof. The antibody, fragment, derivative, or mimetic thereof may bind to an OLFR. The agent may be an antibody that binds to an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B. The agent may be an antibody that binds to an OLFR listed in Table 7. The agent may be an antibody that binds to an OLFR selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2. The antibody, fragment, derivative, or mimetic thereof may bind to a ligand of an OLFR. The antibody, fragment, derivative, or mimetic thereof may bind to a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).

The antibody may be polyclonal, monoclonal, multispecific (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity. Antibodies can be isolated from any suitable biological source, e.g., murine, rat, sheep and canine. The antibody may be a human antibody, humanized antibody, or chimeric antibody. The antibody may be a human monoclonal antibody. The antibody may be a recombinant human antibody.

As used herein, the terms “antibody,” “antibodies” and “immunoglobulin” includes whole antibodies and any antigen binding fragment or a single chain thereof. Thus the term “antibody” includes any protein or peptide containing molecule that comprises at least a portion of an immunoglobulin molecule. The terms “antibody,” “antibodies” and “immunoglobulin” also include immunoglobulins of any isotype, fragments of antibodies which retain specific binding to antigen, including, but not limited to, Fab, Fab′, F(ab)₂, Fv, scFv, dsFv, Fd fragments, dAb, VH, VL, VhH, and V-NAR domains; minibodies, diabodies, triabodies, tetrabodies and kappa bodies; multispecific antibody fragments formed from antibody fragments and one or more isolated. Examples of such include, but are not limited to a complementarity determining region (CDR) of a heavy or light chain or a ligand binding portion thereof, a heavy chain or light chain variable region, a heavy chain or light chain constant region, a framework (FR) region, or any portion thereof, at least one portion of a binding protein, chimeric antibodies, humanized antibodies, single-chain antibodies, and fusion proteins comprising an antigen-binding portion of an antibody and a non-antibody protein. The variable regions of the heavy and light chains of the immunoglobulin molecule contain a binding domain that interacts with an antigen. The constant regions of the antibodies (Abs) may mediate the binding of the immunoglobulin to host tissues. The term “anti-” when used before a protein name, anti-DNABII, anti-IHF, anti-HU, anti-OMP P5, for example, refers to a monoclonal or polyclonal antibody that binds and/or has an affinity to a particular protein. For example, “anti-IHF” refers to an antibody that binds to the IHF protein. The specific antibody may have affinity or bind to proteins other than the protein it was raised against. For example, anti-IHF, while specifically raised against the IHF protein, may also bind other proteins that are related either through sequence homology or through structure homology.

As used herein, “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous antibody population. Monoclonal antibodies are highly specific, as each monoclonal antibody is directed against a single determinant on the antigen. The antibodies may be detectably labeled, e.g., with a radioisotope, an enzyme which generates a detectable product, a fluorescent protein, and the like. The antibodies may be further conjugated to other moieties, such as members of specific binding pairs, e.g., biotin (member of biotin-avidin specific binding pair), and the like. The antibodies may also be bound to a solid support, including, but not limited to, polystyrene plates or beads, and the like.

Monoclonal antibodies may be generated using hybridoma techniques or recombinant DNA methods known in the art. A hybridoma is a cell that is produced in the laboratory from the fusion of an antibody-producing lymphocyte and a non-antibody producing cancer cell, usually a myeloma or lymphoma. A hybridoma proliferates and produces a continuous sample of a specific monoclonal antibody. Alternative techniques for generating or selecting antibodies include in vitro exposure of lymphocytes to antigens of interest, and screening of antibody display libraries in cells, phage, or similar systems.

The term “human antibody” as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies disclosed herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, the term “human antibody” as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. Thus, as used herein, the term “human antibody” refers to an antibody in which substantially every part of the protein (e.g., CDR, framework, C_L, C_Hdomains (e.g., C_H1, C_H2, C_H3), hinge, (VL, VH)) is substantially non-immunogenic in humans, with only minor sequence changes or variations. Similarly, antibodies designated primate (monkey, baboon, chimpanzee, etc.), rodent (mouse, rat, rabbit, guinea pig, hamster, and the like) and other mammals designate such species, sub-genus, genus, sub-family, family specific antibodies. Further, chimeric antibodies include any combination of the above. Such changes or variations optionally retain or reduce the immunogenicity in humans or other species relative to non-modified antibodies. Thus, a human antibody is distinct from a chimeric or humanized antibody. It is pointed out that a human antibody can be produced by a non-human animal or prokaryotic or eukaryotic cell that is capable of expressing functionally rearranged human immunoglobulin (e.g., heavy chain and/or light chain) genes. Further, when a human antibody is a single chain antibody, it can comprise a linker peptide that is not found in native human antibodies. For example, an Fv can comprise a linker peptide, such as two to about eight glycine or other amino acid residues, which connects the variable region of the heavy chain and the variable region of the light chain. Such linker peptides are considered to be of human origin.

As used herein, a human antibody is “derived from” a particular germline sequence if the antibody is obtained from a system using human immunoglobulin sequences, e.g., by immunizing a transgenic mouse carrying human immunoglobulin genes or by screening a human immunoglobulin gene library. A human antibody that is “derived from” a human germline immunoglobulin sequence can be identified as such by comparing the amino acid sequence of the human antibody to the amino acid sequence of human germline immunoglobulins. A selected human antibody typically is at least 90% identical in amino acids sequence to an amino acid sequence encoded by a human germline immunoglobulin gene and contains amino acid residues that identify the human antibody as being human when compared to the germline immunoglobulin amino acid sequences of other species (e.g., murine germline sequences). In certain cases, a human antibody may be at least 95%, or even at least 96%, 97%, 98%, or 99% identical in amino acid sequence to the amino acid sequence encoded by the germline immunoglobulin gene. Typically, a human antibody derived from a particular human germline sequence will display no more than 10 amino acid differences from the amino acid sequence encoded by the human germline immunoglobulin gene. In certain cases, the human antibody may display no more than 5, or even no more than 4, 3, 2, or 1 amino acid difference from the amino acid sequence encoded by the germline immunoglobulin gene.

A “human monoclonal antibody” refers to antibodies displaying a single binding specificity which have variable and constant regions derived from human germline immunoglobulin sequences. The term also intends recombinant human antibodies. Methods to making these antibodies are described herein.

The term “recombinant human antibody”, as used herein, includes all human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies isolated from an animal (e.g., a mouse) that is transgenic or transchromosomal for human immunoglobulin genes or a hybridoma prepared therefrom, antibodies isolated from a host cell transformed to express the antibody, e.g., from a transfectoma, antibodies isolated from a recombinant, combinatorial human antibody library, and antibodies prepared, expressed, created or isolated by any other means that involve splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies can be subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo. Methods to making these antibodies are described herein.

As used herein, chimeric antibodies are antibodies whose light and heavy chain genes have been constructed, typically by genetic engineering, from antibody variable and constant region genes belonging to different species.

As used herein, the term “humanized antibody” or “humanized immunoglobulin” refers to a human/non-human chimeric antibody that contains a minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a variable region of the recipient are replaced by residues from a variable region of a non-human species (donor antibody) such as mouse, rat, rabbit, or non-human primate having the desired specificity, affinity and capacity. Humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. The humanized antibody can optionally also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin, a non-human antibody containing one or more amino acids in a framework region, a constant region or a CDR, that have been substituted with a correspondingly positioned amino acid from a human antibody. In general, humanized antibodies are expected to produce a reduced immune response in a human host, as compared to a non-humanized version of the same antibody. The humanized antibodies may have conservative amino acid substitutions which have substantially no effect on antigen binding or other antibody functions. Conservative substitutions groupings include: glycine-alanine, valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, serine-threonine and asparagine-glutamine.

The terms “polyclonal antibody” or “polyclonal antibody composition” as used herein refer to a preparation of antibodies that are derived from different B-cell lines. They are a mixture of immunoglobulin molecules secreted against a specific antigen, each recognizing a different epitope.

As used herein, the term “antibody derivative”, comprises a full-length antibody or a fragment of an antibody, wherein one or more of the amino acids are chemically modified by alkylation, pegylation, acylation, ester formation or amide formation or the like, e.g., for linking the antibody to a second molecule. This includes, but is not limited to, pegylated antibodies, cysteine-pegylated antibodies, and variants thereof.

The methods, uses, and kits disclosed herein may comprise one or more agents that decrease or inhibit expression or secretion of an inflammatory cytokine. The inflammatory cytokine may be selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2).

Kits

Further disclosed herein are kits comprising any of the agents disclosed herein. In some embodiments, the kit comprises an agent that modulates the activity of an OLFR and instructions for use. Alternatively, or additionally, the kit comprises an agent that increases the activity of an OLFR and instructions for use. The kit may comprise an agent that increases the expression of an OLFR and instructions for use. The kit may comprise an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell and instructions for use. The kit may comprise an agent that decreases the activity of an OLFR and instructions for use. The kit may comprise an agent that decreases the expression of an OLFR and instructions for use. The kit may comprise an agent that decreases or inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell and instructions for use. The kit may comprise a ligand of an olfactory receptor (OLFR) and instructions for use. The kit may comprise an olfactory receptor (OLFR) agonist and instructions for use. The kit may comprise an olfactory receptor (OLFR) antagonist and instructions for use. The kit may comprise octanal and instructions for use. The kit may comprise citral and instructions for use. The kit may comprise a gene silencing agent that targets an olfactory receptor (OLFR) and instructions for use. The kit may comprise a gene silencing agent that targets a ligand of an olfactory receptor (OLFR) and instructions for use. The kit may comprise a gene silencing agent that targets one or more proteins selected from the group consisting of a receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal) and instructions for use.

The kits disclosed herein may further comprise one or more pharmaceutically acceptable carriers. “Pharmaceutically acceptable carriers” refers to any diluents, excipients, or carriers that may be used in the compositions disclosed herein. Pharmaceutically acceptable carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances, such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field. They may be selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices.

Administration

The methods, uses, and kits disclosed herein may comprise administering an agent or instructions to administer an agent to a subject in need thereof.

“Administration” can be effected in one dose, continuously or intermittently throughout the course of treatment. Methods of determining the most effective means and dosage of administration are known to those of skill in the art and will vary with the composition used for therapy, the purpose of the therapy, the target cell being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician. Suitable dosage formulations and methods of administering the agents are known in the art. Route of administration can also be determined and method of determining the most effective route of administration are known to those of skill in the art and will vary with the composition used for treatment, the purpose of the treatment, the health condition or disease stage of the subject being treated, and target cell or tissue. Non-limiting examples of route of administration include oral administration, nasal administration, injection, and topical application.

An agent of the present disclosure can be administered for therapy by any suitable route of administration. It will also be appreciated that the optimal route will vary with the condition and age of the recipient, and the disease being treated. The term “effective amount” refers to a quantity sufficient to achieve a desired effect. In the context of therapeutic or prophylactic applications, the effective amount will depend on the type and severity of the condition at issue and the characteristics of the individual subject, such as general health, age, sex, body weight, and tolerance to pharmaceutical compositions. In the context of an immunogenic composition, in some embodiments the effective amount is the amount sufficient to result in a protective response against a pathogen. In other embodiments, the effective amount of an immunogenic composition is the amount sufficient to result in antibody generation against the antigen. In some embodiments, the effective amount is the amount required to confer passive immunity on a subject in need thereof. With respect to immunogenic compositions, in some embodiments the effective amount will depend on the intended use, the degree of immunogenicity of a particular antigenic compound, and the health/responsiveness of the subject's immune system, in addition to the factors described above. The skilled artisan will be able to determine appropriate amounts depending on these and other factors.

As used herein, the terms “treat” or “treatment” may refer to any prevention or delay in onset, reduction in the frequency or severity of symptoms, amelioration of symptoms, improvement in patient comfort or function, decrease in severity of the condition or disease state, decrease in the occurrence of a given condition or disease or condition or disease symptoms in a patient etc. The effect of treatment can be compared to an individual or pool of individuals not receiving a given treatment, or to the same patient prior to, or after cessation of, treatment. As indicated above, the treatment may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.

In some embodiments, a method of treatment results in partial or complete destruction of the neoplastic, tumor, cancer or malignant cell mass; a reduction in volume, size or numbers of cells of the neoplastic, tumor, cancer or malignant cell mass; stimulating, inducing or increasing neoplastic, tumor, cancer or malignant cell necrosis, lysis or apoptosis; reducing neoplasia, tumor, cancer or malignancy cell mass; inhibiting or preventing progression or an increase in neoplasia, tumor, cancer or malignancy volume, mass, size or cell numbers; or prolonging lifespan. In some embodiments, a method of treatment results in reducing or decreasing severity, duration or frequency of an adverse symptom or complication associated with or caused by the neoplasia, tumor, cancer or malignancy. In some embodiments, a method of treatment results in reducing or decreasing pain, discomfort, nausea, weakness or lethargy. In some embodiments, a method of treatment results in increased energy, appetite, improved mobility or psychological well-being.

In certain embodiments, a method of treatment comprises administering a therapeutically effective amount of an agent to a subject, wherein the agent modulates expression or activity of one or more olfactory receptor listed in any of Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, FIG. 2A, and FIG. 2B. By “therapeutically effective amount” as used herein is meant a dose that produces effects for which it is administered (e.g. treating or preventing a disease or disorder). The exact dose and formulation will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Remington: The Science and Practice of Pharmacy, 20th Edition, Gennaro, Editor (2003), and Pickar, Dosage Calculations (1999)). For example, for the given parameter, a therapeutically effective amount will show an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Therapeutic efficacy can also be expressed as “-fold” increase or decrease. For example, a therapeutically effective amount can have at least a 1.2-fold, 1.5-fold, 2-fold, 5-fold, or more effect over a standard control. A therapeutically effective dose or amount may ameliorate one or more symptoms of a disease. A therapeutically effective dose or amount may prevent or delay the onset of a disease or one or more symptoms of a disease when the effect for which it is being administered is to treat a person who is at risk of developing the disease.

The present inventions further provide novel agents identified by the assays described herein and use of such agent in the methods of treatment described herein.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

All applications, publications, patents and other references, GenBank citations and ATCC citations cited herein are incorporated by reference in their entirety. In case of conflict, the specification, including definitions, will control.

All of the features disclosed herein may be combined in any combination. Each feature disclosed in the specification may be replaced by an alternative feature serving a same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, disclosed features (e.g., compound structures) are an example of a genus of equivalent or similar features.

As used herein, the singular forms “a”, “and,” and “the” include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to “a first, second, third, fourth, fifth, etc. predictor gene” or a “positive or negative predictor gene” includes a plurality of such first, second, third, fourth, fifth, etc., genes, or a plurality of positive and/or negative predictor genes.

As used herein, all numerical values or numerical ranges include integers within such ranges and fractions of the values or the integers within ranges unless the context clearly indicates otherwise. Thus, to illustrate, reference to a range of 90-100%, includes 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., as well as 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc., and so forth.

Reference to a number with more (greater) or less than includes any number greater or less than the reference number, respectively. Thus, for example, a reference to less than 30,000, includes 29,999, 29,998, 29,997, etc. all the way down to the number one (1); and less than 20,000, includes 19,999, 19,998, 19,997, etc. all the way down to the number one (1).

As used herein, all numerical values or ranges include fractions of the values and integers within such ranges and fractions of the integers within such ranges unless the context clearly indicates otherwise. Thus, to illustrate, reference to a numerical range, such as a percentage range, 90-100%, includes 91%, 92%, 93%, 94%, 95%, 95%, 97%, etc., as well as 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc., and so forth. Reference to a range of 1-5 fold therefore includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, fold, etc., as well as 1.1, 1.2, 1.3, 1.4, 1.5, fold, etc., 2.1, 2.2, 2.3, 2.4, 2.5, fold, etc., and so forth.

Reference to a series of ranges includes ranges which combine the values of the boundaries of different ranges within the series. Thus, to illustrate reference to a series of ranges of 2-72 hours, 2-48 hours, 4-24 hours, 4-18 hours and 6-12 hours, includes ranges of 2-6 hours, 2-18 hours, 2-24 hours, etc., and 4-27 hours, 4-48 hours, 4-6 hours, etc.

The invention is generally disclosed herein using affirmative language to describe the numerous embodiments and aspects. The invention also specifically includes embodiments in which particular subject matter is excluded, in full or in part, such as substances or materials, method steps and conditions, protocols, or procedures. For example, in certain embodiments or aspects of the invention, materials and/or method steps are excluded. Thus, even though the invention is generally not expressed herein in terms of what the invention does not include aspects that are not expressly excluded in the invention are nevertheless disclosed herein.

A number of embodiments of the invention have been described. Nevertheless, one skilled in the art, without departing from the spirit and scope of the invention, can make various changes and modifications of the invention to adapt it to various usages and conditions. Accordingly, the following examples are intended to illustrate but not limit the scope of the invention claimed.

EXAMPLES
Example 1: Effect of Citral on Expression of Inflammatory Genes (CCL2, CCL4, TNF and iNOS)

In this example, the effects of citral on CCL2, CCL4, TNF and iNOS expression in vascular macrophages in Apoe−/− mice was investigated. The effect of citral on atherosclerosis in Apoe−/− mice fed a high fat western diet, a widely used model of atherosclerosis, was also investigated in this example

Gene expression analysis was performed by harvesting whole aortas from apoE^−/− mice kept on western diet (WD) for 2 weeks and treating for 12h with DMSO (Ctrl), citral (Cit, 100 μM), octanal (Oct, 10 μM in DMSO) or lipopolysaccharide (lps, 0.5 μg/mL in DMSO) alone or in combination. After the incubation, aortas were transferred in Trizol reagent (1 ml) and digested with gentleMACS™ Dissociator (Millteny). Total RNA was then purified with RNAse Micro kit (Qiagen) and reverse transcribed using the Omniscript reverse transcriptase kit (Qiagen). Real-time PCR reaction was performed following the RT²Sybr green gene expression assay protocol (Qiagen). RT2 SYBR Green qPCR mastermix mix and premade RT²qPCR Primer Assay for mouse GAPDH, CCL2, CCL4, TNF, and iNOS were used. Data were normalized to the expression levels of the housekeeping gene GAPDH. FIG. 1A: shows the results of a gene expression analysis of CCL2, CCL4, TNF and iNOS after treatment with the Olfr2 inhibitor citral alone or in combination with octanal and LPS. As shown in FIG. 3A, citral completely blocked the increase in CCL2, CCL4, TNF and iNOS, both in the presence and absence of LPS.

The effect of citral on atherosclerosis in Apoe−/− mice fed a high fat western diet, a widely used model of atherosclerosis, was investigated. Briefly, ApoE^−/− Mice (10 weeks old) were fed WD for 4 weeks before the inhibitor treatment, citral, was started. Citral at 10 mg/kg was diluted in 100 uL of PBS and injected I.P. every 3 days for 4 weeks for a total of 12 injections. During this time, mice continue to eat WD for a total of 8 weeks. After that, the mice were sacrificed and harvested for aorta explant and pinning FIG. 1B shows the results of an atherosclerosis lesion evaluation (% and number of pixels with lesions) after the treatment with OLFR2 inhibitor citral. FIG. 1C shows pictures of pinned aortas of mice treated with citral or saline (untreated). As shown in FIG. 1B, the citral-treated Apoe−/− mice showed significantly reduced atherosclerotic lesions, from ˜8% of the aortic area to ˜5% (P<0.02). Thus, blocking Olfr2 is anti-atherosclerotic, showing that Olfr2 contributes to atherosclerosis.

Example 2: Transcriptomic Study of Vascular Macrophages

Atherosclerosis is an inflammatory disease of the arterial wall driven by macrophages and other immune cells. Olfactory receptors (Olfrs) are G-protein coupled receptors expressed in olfactory epithelial cells and are responsible for the sense of smell. To better understanding atherosclerosis, a transcriptomic study of vascular macrophages was performed.

In a transcriptomic study of vascular macrophages sorted from aortas of atherosclerosis-prone Apoe^−/− mice, hundreds of Olfrs, Gαolf (Gnal), Acy3, Reep3, Rtp1, Rtp2 and the cyclic nucleotide-gated ion channel subunits Cnga1-4 and Cngb1 were unexpectedly found to be expressed (Table 2). Some of these genes were detectable even in aortic macrophages from mice without atherosclerosis, and many were upregulated in response to LPS (FIG. 2A, Table 1).

FIG. 2A depicts a heat map of Olfr genes (total 1123) expressed in mouse vascular macrophages and several other tissue macrophages, DCs and blood monocytes [data were normalized through Gapdh expression ranking (=1), by row]. Several microarray datasets (Affymetrix mouse gene 1.0 ST array type) were used for the comparison: GSE68968 Vascular Mφ; GSE77104 BMDMs, GSE43075 peritoneal (PT) Mφ; GSE100393 Small Intestine (SI) Mφ; GSE15907 Lung Mφ; GSE15907 Spleen (red pulp) Mφ; GSE15907 Microglia; GSE100393 SI DCs; GSE15907 Lung DCs; GSE15907 mesenteric LN (MLN) DCs; GSE15907 blood classical (CM) and non-classical monocyte (NCM) subpopulations. The one minus Pearson correlation clustering of rows and columns is displayed. Olfr2, Rtp1, Rtp2, Reep3, Acy3, Gnal, Cnga1-4 and Cngb1 are highlighted.

In published transcriptomes of other tissue macrophages (small intestinal (SI) macrophages, untreated intraperitoneal (IP) macrophages or stimulated with LPS, lung CD11b-macrophages, splenic red pulp macrophages, microglia), dendritic cells (DCs) (small intestinal DCs, mesenteric lymph node (MLN) DCs, lung DCs) and monocytes (classical (CM), non-classical (NCM), both MHC-II+ and −) much fewer Olfrs were expressed. The list of normalized Olfrs expression and accessory molecules can be found in Table 1.

FIG. 2B displays a heat map of expressed Olfrs with known human orthologues. Of the 1123 known mouse Olfrs, 582 have known human orthologues (Olfrs sharing the same human orthologue are included), 280 of which (48%) were expressed in vascular macrophages from LPS treated mice (FIG. 2B).

This experiment demonstrates that vascular macrophages express hundreds of olfactory receptors and accessory molecules needed for Olfr signalling and trafficking.

Example 3: Olfr2 and Atherosclerosis

As shown in Example 2, vascular macrophages express hundreds of olfactory receptors including Olfr2, a receptor for octanal. They also express Rtp1, Rtp2, Reep3, Acy3 and Gnal, accessory molecules needed for Olfr signaling and trafficking. Ligation of the human orthologue of Olfr2 (OR6A2), expressed in human atherosclerotic plaque and in human monocyte-derived macrophages, is strongly pro-inflammatory. In this example, the role of Olfr2 in atherosclerosis is investigated.

Olfr2 (human orthologue: OR6A2) is investigated in this example because (1) its expression is increased in LPS treated vascular macrophages, (2) is expressed in bone marrow-derived macrophages (BMDMs), (3) has known ligands (aliphatic aldehydes including octanal), (4) has a known inhibitor (citral), (5) has a human orthologue (OR2A6), which (6) is expressed in human carotid endarteriectomy samples and human monocyte-derived macrophages.

Olfr2 binds medium-chain aliphatic aldehydes such as octanal with an EC50 of ˜10 μM^15,16. Octanal is a 8-carbon aldehyde also known as fatty aldehyde that is produced by reduction of the carboxy group of caprylic acid (octanoic acid) or via lipid peroxidation during oxidative stress¹⁷.

Olfr2 expression in BMDMs was investigated. Briefly, bone marrow cells from Apoe^−/− mice were stimulated with MCSF (20 ng/ml) for 7 d to generate BMDMs, which were left untreated or incubated with the Olfr2 agonist octanal (Oct, 10 μM), LPS, (500 ng/mL), or with both for 12 h.

In mouse BMDMs, Olfr2 mRNA (FIG. 3A) and protein expression was found by western blot (FIG. 3B). Olfr2 mRNA and protein expression was enhanced by bacterial lipopolysaccharide (LPS), octanal and potentiated by both combined. Flow cytometry (FIGS. 3C-D) demonstrated surface expression of Olfr2. Cell surface and intracellular Olfr2 expression was confirmed by immunofluorescence (FIG. 3E).

Next, Olfr2 expression in aortas harvested from western-type diet (WD)-fed male mice (n=5) was investigated¹⁸. Briefly, whole aortas were harvested from Apoe^−/− mice fed western-like diet (WD) for 2 weeks and treated as described above. Relative expression of Olfr2 quantified by real time PCR analysis of Olfr2 expression normalized to expression of Gapdh and untreated control.

In addition, Rtp1 and Rtp2 expression in aortas harvested from Apoe−/− mice was investigated. Briefly, explanted aortas of Apoe−/− mice treated for 12h with Oct (10 μM) and/or lipopolysaccharide (LPS, 500 ng/mL). Rtp1 and Rtp2 expression was assessed by qPCR as described above. N=3 independent experiments (relative expression calculated by 2^−ΔΔCtmethod). Data are presented as means±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test.

As shown in FIGS. 3F and 4A-B, aortic Olfr2 mRNA, Rtp1 and Rtp2 mRNA were found to be induced by LPS treatment ex vivo and significantly enhanced by adding octanal. Olfr2 expression was confirmed at the protein level on F4/80⁺ vascular macrophages purified form aortas as elsewhere described¹⁹(FIG. 3G-H).

Olfr2 expression in T cells and B cells was also investigated. Briefly, whole aortas were harvested from Apoe−/− mice kept on western diet (WD) for at least 2 weeks incubated with Octanal (Oct, 10 μM) and lipopolysaccharide (LPS, 500 ng/mL) for 12h. Cells were harvested and stained for Olfr2 detection (as described in FIG. 3E) and analyzed by flow cytometry (LSRII, BD Biosciences). Olfr2-AF488 Median Fluorescence Intensity (MFI) of B cells (CD45+, Live, TCRβ−, CD19+) and CD4+ T cells (CD45+, Live, TCRβ+, CD4+) is reported. N=5 per group. Notably, other aortic immune cell populations such as CD4⁺ T cells and CD19⁺ B cells, did not show significant Olfr2 expression (FIGS. 5A-B). Immunofluorescence experiments in aortic whole mounts of WD-fed mice confirmed the Olfr2 expression in many, but not all CD68⁺ macrophages (FIG. 3I).

In addition, Olfr2 expression and function on blood mononuclear cells was investigated. Briefly, Apoe−/− mice blood harvested by cardiac puncture was red blood cells lysed, and incubated with Octanal (Oct, 10 μM) and lipopolysaccharide (LPS, 500 ng/mL) for 12h. Cells were harvested and stained for Olfr2 detection (as described in FIG. 3E) and analyzed by flow cytometry (LSRII, BD Biosciences). Olfr2-AF488 Median Fluorescence Intensity (MFI) of total monocytes (CD45+, Live, TCRβ−, CD19−, CD115+), classical monocytes (CD45+, Live, TCRβ−, CD19−, CD115+, Ly6C+), non classical monocytes (CD45+, Live, TCRβ−, CD19−, CD115+, Ly6C−), B cells (CD45+, Live, TCRβ−, CD19+) and CD4+ T cells (CD45+, Live, TCRβ+, CD4+) is reported. n 5-6 per group. Data are presented as means±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test. Olfr2 protein was found to be expressed on circulating classical (CD115⁺Ly6C⁺) and non-classical (Cd115⁺Ly6C⁻) blood monocytes (FIG. 6A).

To assess the functional properties of Olfr2 in monocytes, cells were enriched form Apoe−/− mice blood by the negative selection. Purified monocytes were then incubated as described above. TNF expression (TNF-PE) was evaluate by intracellular staining protocol by flow cytometry. Classical and non-classical monocytes were divided as previously described (Live, CD115+, LyC6+, and LyC6− respectively). FIG. 6B shows Olfr2 function in monocytes reported as TNF MFI multiplied to the cell events. n 5 per group. Data are presented as means±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test.

The role of Olfr2 ligation on inflammatory responses was investigated by measuring intracellular free calcium (Can in vascular macrophages. Briefly, mouse aortic cell suspensions were loaded with 2 μM Fluo-4 at 37° C. for 30 min, then washed and incubated with cell surface markers at RT for 20 min CD45⁺, live, dump channel⁻ (TCRb⁻, CD19⁻), F4/80⁺ macrophages were analyzed by flow cytometry. Olfr2 agonist Oct (10 μM), and antagonist Cit (100 μM) alone or combined (Oct+Cit) were added 60 seconds (s) after the acquisition started. DMSO (0.1%) was injected as a control (Ctrl).

To test the functionality of Olfr2, time-resolved calcium flux in mouse vascular macrophages by flow cytometry was studied (FIG. 7A). Octanal induced a highly significant increase in intracellular free calcium at 100 and 125 s after injection, consistent with the known calcium dynamics of Olfrs¹⁵(FIG. 7B). This calcium flux was completely blocked by the Olfr2 inhibitor citral^9,16(FIG. 7B). No calcium signal was detected in other immune cells (FIGS. 8A-B). FIG. 8A shows dump channel+ cells (TCRb+, and CD19+), loaded with 2 μM Fluo-4 before and after addition of Olfr2 agonist octanal (Oct 10 μM), and antagonist Citral (Cit 100 μM) alone or combined (Oct+Cit). Oct, and Cit injected at 60 seconds. Whole aortas were digested, stained with Fluo4 (2 μM) at 37° C. for 30 min, then washed and incubated with cell surface markers at RT for 20 min CD45+, live, dump channel+(TCRb+, and CD19+) cells were analyzed by flow cytometry. FIG. 8B shows the time average Median Fluorescence Intensity (MFI) of Fluo-4 is reported. SD is calculated among the cells for each time point (n 20-50). The analysis is made out one of three experiments.

An early step in atherosclerosis is the subendothelial retention of lipoproteins, which then triggers a non-resolving inflammatory process that over time drives plaque progression^20,21. Macrophages contribute to the inflammatory response and plaque formation by producing pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), chemokines including CCL2 and CCL4, and inducible nitric oxide synthase (iNOS)²². Most vascular macrophages derive from CX3CR1⁺ embryonic precursors with a postnatal contribution from bone marrow-derived monocytes that colonize the tissue immediately after birth^23,24. During adulthood, vascular macrophages proliferate locally²⁵. In atherosclerotic mice, plaques contain several phenotypically distinct macrophage subsets^26-28. Specifically, four major macrophage populations were found in atherosclerotic aortas: a resident-like, an inflammatory and a TREM2⁺ subset²⁶and foam cells²⁸.

To test physiologic effects of Olfr2 activation in situ, explanted whole aortas of mice (n=5 per group) were treated with octanal with or without LPS. Briefly, whole aortas were left untreated or incubated with the Olfr2 agonist octanal (Oct, 10 μM), LPS, (500 ng/mL), or with both for 12 h. Quantitative Real time PCR reaction was performed to detect Ccl2, Ccl4, Tnf, and Nos2 gene expression. Relative expression was normalized to Gapdh expression and the untreated control. As shown in FIG. 7C, octanal treatment induced mRNA expression of the inflammatory chemokines Ccl2 (MCP-1) and Ccl4 (MIP-1β), the inflammatory cytokine Tnf and the inflammatory nitric oxide synthase iNOS (Nos2). In all cases, octanal enhanced the LPS-induced expression of these inflammatory molecules, peaking at 3-10 μM (FIG. 7C, FIGS. 9A-B). Conversely, the Olfr2 inhibitor citral was effective at curbing inflammatory mediator expression in explanted aortas incubated with octanal (FIG. 7D). Citral did not affect Olfr2 mRNA expression (data not shown). Octanal and LPS also enhanced the secretion of TNF, CCL2 and CCL4 protein into the supernatant of treated aortas (FIG. 7E). TNF secretion by vascular macrophages (F4/80+) was confirmed by intracellular staining using flow cytometry (FIG. 7F). Similar results were observed in classical Ly6C⁺ monocytes and not in non-classical Ly6C⁻ monocytes (FIG. 6B).

Macrophages are known producers of one of the most prominent cytokines driving atherosclerosis, IL-1β²⁹. IL-1β production and secretion requires assembly of the inflammasome, a cytoplasmic complex containing several proteins that serves as a molecular platform for activation of the cysteine protease caspase^30,31. To test whether octanal induced IL-1β secretion in macrophages, BMDMs were primed with low-dose LPS (50 ng/mL) for 18 h followed by exposure to octanal alone or together with citral. IL-1β protein in the supernatant was quantified by a cytokine bead array. Data are presented as mean±SEM. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001. p calculated by One-Way ANOVA test, Tukey's multiple comparisons test and unpaired t-test. As shown in FIG. 7G, octanal (10 μM) strongly increased the release of IL-1β into the supernatant, which was inhibited by citral. These data suggest a possible enhancement of the inflammasome activation by octanal.

Next, mass spectrometry was used to measure octanal in blood plasma of wild-type and Apoe−/− mice on chow (CD) or western (WD) diet. Briefly, murine blood plasma was analyzed for octanal by derivatization and stable isotope dilution LC/MS/MS. [²H₁₆]octanal was spiked to plasma before derivatization reaction as internal standard. Stable isotope dilution HPLC with on-line tandem mass spectrometry (LC/MS/MS) (FIG. 10A) showed detectable levels of octanal in all mice. In plasma of C57BL/6J mice on CD, octanal ranged between 1.5 and 2.5 μM (FIG. 10B). The octanal level was significantly increased to an average of 3.5 μM in mice fed WD (FIG. 10B). Octanal was also elevated in Apoe^−/− mice receiving CD and WD (FIG. 10C). Plasma of healthy human donors also contained octanal at an average concentration of 1.5 μM (±0.82, n=5).

To test a possible impact of Olfr2 on atherosclerosis in vivo, male Apoe^−/− mice were fed WD for 8 weeks and injected octanal (10 μg/g) intraperitoneally for the last 4 weeks every three days for a total of 12 injections. En face staining of aortic arches showed that octanal treatment more than doubled lesion size (FIGS. 10D and E). Octanal had no effect on total cholesterol, LDL cholesterol, HDL cholesterol or triglycerides (FIG. 11A). Similarly, in a loss-of-function experiment, male Apoe^−/− mice were treated with citral (10 μg/g, 12 injections over 4 weeks), which reduced the size of atherosclerotic lesions by ˜40% (FIGS. 10F and G). Citral treatment like octanal had no effect on other parameters (FIG. 11A). This finding suggests that endogenous levels of volatile octanal are sufficient to induce a pathophysiologically relevant activation of Olfr2.

Since the expression and the trafficking of most olfactory receptors and specifically Olfr2 is regulated by Rtp1 and Rtp2¹⁹, whether their deletion would influence atherosclerotic lesion size was investigated. Male Ldlr^−/− mice were lethally irradiated and reconstituted with bone marrow cells from Rtp1/Rtp2^−/−, Rtp1/Rtp2^+/− or Rtp1/Rtp2^+/+ mice. Western blot and flow cytometry analysis confirmed that Olfr2 expression was significantly reduced in BMDMs of Rtp1/Rtp2^−/− mice (FIGS. 10H and I; FIG. 12). After 2 weeks recovery, mice were fed a high-fat diet for 12 weeks. Circulating metabolic parameters (total cholesterol, high-density lipoprotein-cholesterol, and triglycerides), blood leukocyte counts and animal weights were similar between the 3 groups (FIG. 12). Aortic arch lesions in Rtp1/Rtp2^−/− chimeric mice were significantly reduced compared to Rtp1/Rtp2^+/+ recipient mice (FIG. 10J). Taken together, Olfr2 and possibly other Olfrs regulated by Rtp1 and 2 promote atherosclerosis in mice. Inhibition of Olfr2 limits atherosclerosis in mice.

Having shown that human plasma contains octanal, the applicability of the mouse to human atherosclerosis was investigated. To this end, the transcriptomes of carotid artery plaques deposited in the Biobank of Karolinska Endarterectomy (BiKE) (GSE21545) were interrogated. OR6A2 mRNA, the human orthologue of mouse Olfr2, was expressed in all 126 plaque samples (RMA>3) and in 83 of 97 (85%) of peripheral blood mononuclear cell (PBMC) samples (FIG. 13A).

Next, whether human monocyte-derived macrophages (hMDMs) express OR6A2 was investigated. OR6A2 mRNA expression was detectable, increased by LPS and further augmented by adding octanal (FIG. 13Bi). OR6A2 protein surface expression in hMDMs was confirmed by flow cytometry (FIG. 13Bii and iii). Immunostaining suggests that OR6A2 expression in LPS+octanal-treated hMDMs may be polarized (FIG. 13C).

Octanal treatment of hMDMs induced mRNA expression of pro-inflammatory molecules including TNF, IL6 and NOS2 (FIG. 13D). In all cases, octanal enhanced the LPS-induced expression of these inflammatory molecules and their secretion as detected in the supernatant (FIG. 13E). Like in mouse macrophages, inflammasome activation was potentiated by octanal, resulting in a highly significant increase of IL-1β in the supernatant, which was partially but significantly inhibited by citral (FIG. 13F).

OR6A2 is not the only receptor for octanal (Araneda, R. C., Kini, A. D. & Firestein, S. The molecular receptive range of an odorant receptor. Nat Neurosci 3, 1248-1255, doi:10.1038/81774 (2000); Li, Y. et al. Aldehyde recognition and discrimination by mammalian odorant receptors via functional group-specific hydration chemistry. ACS Chem Biol 9, 2563-2571, doi:10.1021/cb400290u (2014)). To test whether OR6A2 is relevant for octanal-mediated hMDM activation, OR6A2 was silenced in hMDMs by small interference RNAs (SiOR6A2). LPS- and ocatanal-treated hMDMs exhibited reduced expression of IL6, NOS2 and TNF compared to hMDMs treated with scrambled siRNAs (SiCtrl) (FIG. 13G).

The discovery of a new class of GPCRs, Olfrs, that enhance atherosclerosis suggest a new class of drug targets. The octanal receptor Olfr2 and its human orthologue OR6A2 are expressed on aortic vascular macrophages, mouse BMDMs, human hMDMs and human atherosclerotic lesions. Olfr2/OR6A2 expression is increased by LPS and further elevated in the presence of octanal at the mRNA and protein level. Olfr2 ligation by octanal induces inflammatory cytokines and chemokines in mouse and human macrophages. Injecting mice with the known Olfr2 agonist octanal exacerbated atherosclerosis, while blocking Olfr2 by citral or impairing Olfr trafficking by Rtp1/Rtp2^−/− protected mice from atherosclerosis. Since blocking Olfr2 or impairing the trafficking of Olfrs suggests that octanal and perhaps other natural endogenous volatile compounds significantly drive atherosclerosis in vivo. Relevance to human atherosclerosis is suggested by the decreased inflammatory activation of octanal-stimulated hMDMs depleted of OR6A2, the observation of octanal in human blood serum and the presence of OR6A2 in all 126 human atherosclerotic plaques tested.

Since Olfrs have no known role yet in host defense, the examples demonstrate that drug-like small molecules targeting Olfr2, other Olfrs, and downstream signaling pathways might be viable therapeutic targets for the treatment, prevention and reversal of atherosclerosis.

Methods

Animals

Apoe^−/−, Ldlr^−/− and wt mice on C57BL/6J background were purchased from Jackson Laboratories. Rtp1/Rtp2^−/+ breeding pairs were kindly provided by Dr. Hiroaki Matsunami from the Duke University Medical Center. Gender-matched mice (8-10 weeks old) were used in all experiments unless specified. Mice were housed in a conventional environment and had access to chow diet ad libitum. From 8-10 weeks of age on, Apoe^−/− and C57BL/6J mice were fed a western-like diet (WD) with 42% from fat (Harlan Labs Cat #: TD.88137) and remained on WD until sacrifice. Ldlr^−/− male mice (8-10 weeks of age) were used for bone marrow transplantation experiments as specify in detail below.

All animal experiments were conducted in accordance with the institutional guideline at the La Jolla Institute for Immunology animal facility.

Mouse Aorta Ex Vivo Culture

Each aorta was surgically removed and carefully cleaned of adipose tissue in situ. Aortas were either kept whole or enzymatically digested as previously described¹⁸. In brief, aortas were cut into small pieces and individually digested 1h at 37° C. in HBSS containing 450U/mL Collagenase I (Sigma Aldrich), 250 U/mL Collagenase XI (Sigma Aldrich), 120 U/mL Hyaluronidase (Sigma Aldrich), and 120 U/mL DNase I (Worthington). The digested aortic cell suspension was filtered through a 50 μm cell strainer (Partec) and washed with warm 37° C. RPMI-1640 medium (Gibco-ThermoFischer) supplemented with 10% fetal bovine serum (FBS) and 1% Penicillin/Streptomycin solution (Gibco-ThermoFischer) (from here on referred to as culture medium).

Whole aortas or digested aortic cells were cultured in culture medium for further stimulation as described below.

Mouse Blood Collection and Leukocyte Isolation

Mouse blood was collected in ethylenediamine tetraacetic acid (EDTA)-coated tubes (Sarstedt) by cardiac heart puncture during organ harvest.

Circulating leukocytes were obtained from full mouse blood incubated with 10 mL of 1× Red Blood Cell (RBC) Lysis Buffer (eBioscience) for 10 min at room temperature (RT) in the dark. Subsequently, cells were washed twice with culture medium and used for further flow cytometry studies.

Bone Marrow Cell Isolation and Generation of BMDMs

Mouse bone marrow was isolated from femurs and tibiae flushed with 5 ml ice cold RPMI-1640 medium. Bone marrow cells were passed through a 70 μm cell strainer (BioPioneer) and resuspended at 1×10⁶cells/ml in culture medium supplemented with 20 ng/mL of mouse recombinant macrophage-colony stimulating factor (M-CSF; Peprotech). Cells were cultured at 37° C. and 5% CO₂in a 3.8 cm²(Thermo Fischer Scientific) dish. After 3 days, 5 ml of fresh medium were added to the culture. On day 7, floating cells were discarded and adherent cells used for further studies.

Human Monocyte Derived Macrophages (hMDMs)

Peripheral blood mononuclear cells (PBMCs) were isolated from EDTA-venous blood of informed healthy donors (25-50 years old) from La Jolla Institute for Immunology's in-house Normal Blood Donor Program (NBDP), using a Ficoll-Paque (GE Healthcare) standard separation protocol. Human monocytes were enriched from PBMCs by the EasySep™ Human Monocyte Isolation Kit (StemCell) according to the manufacturer's instructions. Enriched monocytes were incubated with culture medium supplemented with 50 ng/ml rhM-CSF at 37° C. and 5% CO₂for 7 days. Differentiated macrophages at day 7 were used for further studies.

Olfr2 Functional Ex Vivo and In Vivo Experimental Procedures

Ex Vivo Analysis

Octanal, citral, and dimethylsulfoxide (DMSO), were purchased from Sigma. All chemicals used were of analytical grade or the highest grade available. Citral and octanal were reconstituted/diluted in DMSO at 10 mM conc.

Apoe^−/− mice were fed WD for 2 weeks before sacrifice for aorta explant culture. Whole aortas were incubated in culture medium with DMSO (0.1% as a vehicle), octanal (Oct, 10 μM), LPS (500 ng/mL) alone or octanal and LPS combined (LPS+Oct) for 12 h at 37° C. and 5% CO₂. Subsequently, aortas were collected and further processed as below discussed for RNA extraction, and flow cytometry analysis. Culture supernatants were collected, aliquoted, and frozen at −80° C. until further analysis.

In Vivo Studies

Male Apoe^−/− mice (9 to 10 wks old) were fed WD for 4 weeks. Oct or Cit were diluted in sterile phosphate buffered saline (PBS) (Gibco) at a final concentration of 10 μg/g. 100 μl were injected intraperitoneally (i.p.) every 3 days for 4 weeks (12 injections total) while maintaining WD administration. PBS+0.1% DMSO (Sigma Aldrich) was injected as a vehicle control following the same protocol. Mice were sacrificed, perfused with PBS implemented with 2% heparin (Fresenius Kabi USA, LLC) and aortas removed for en face atherosclerotic lesion assessment. Mouse whole blood (heart puncture) was collected in EDTA tubes. Leukocyte blood counts were determined with HemaVet 950 (Drew Scientific). Plasma was collected from blood centrifuged at 3000 g for 15 min at 4° C. and stored at −80° C. until further analysis.

Bone Marrow Transplantation

Ten-week-old Ldlr^−/− male mice were irradiated twice 2-4h apart with 550 rads X-ray irradiation to induce systemic medullar aplasia. Irradiated mice were repopulated intravenously (tail vein) with bone marrow cells (5×10⁶cells) isolated from femurs and tibias of 10-week-old Rtp1/Rtp2^+/+, Rtp1/Rtp2^+/−, Rtp1/Rtp2^−/−mice, respectively. After a 2-week recovery period, mice were fed a high cholesterol diet (product number D12108C, Research Diets Inc.) for additional 12 wks. At the end of the 12 wks mice were sacrificed, perfused with PBS implemented with 2% heparin (Fresenius Kabi USA, LLC) and aortas removed for en face atherosclerotic lesion assessment. Blood was collected in EDTA tubes by cardiac heart puncture. Leukocyte blood counts were determined with HemaVet 950 (Drew Scientific). Plasma was collected from blood centrifuged at 3000 g for 15 min at 4° C. and stored −80° C. until further analysis.

Femurs and tibias were also collected for BMDMs differentiation flowing the same protocol already described, and furtherly used for flow cytometry and western blot analysis of Olfr2 expression.

Atherosclerosis Quantification in Whole Aortas

After explant, each aorta was pinned out after 4% paraformaldehyde incubation at room temperature for at least 2 hours Staining for atherosclerotic plaque was performed by incubating samples in Sudan IV. Microphotographs of the luminal (endothelial) aspect were of the aortic surface were analyzed using Photoshop CS (Adobe Systems). Atherosclerotic lesion size measurement was performed by blinded investigators using Image-Pro Premier software (Media Cybernetics).

Lipid Analysis

Lipid analysis of collected plasma was performed by IDEXX BioResearch.

Quantitative Real Time PCR

BMDMs and hMDMs were incubated in culture media for 12 h at 37° C. and 5% CO₂with Oct, (10 μM), LPS (500 ng/mL) alone or combined with Oct (LPS+Oct) and DMSO (0.1%) as a control and lysed with Qiazol (500 μL; Qiagen) Similarly, whole aortas incubated as previously described were transferred into Qiazol (500 μl; Qiagen) and digested with gentleMACS™ Dissociator (Miltenyi).

RNA extraction was performed using a Qiazol/RNAeasy micro kit hybrid protocol (Qiagen).

Total RNA was quantified using a nanodrop spectrophotometer (Peqlab) and 500 ng were reverse transcribed into cDNA using Omniscript reverse transcriptase (Qiagen). Real time PCR reactions were performed according to the RT²SYBR green gene expression assay protocol (Qiagen). RT2 SYBR Green qPCR master mix and premade RT²qPCR Primer Assays for mouse Olfr2, Rtp1, Rtp2, Ccl2, Ccl4, Tnf, Nos2 and Gapdh were used. Similarly, real time PCR analysis of hMDMs samples was performed following the RT²SYBR green gene expression assay protocol (Qiagen), applying RT²SYBR Green qPCR master mix and premade RT²qPCR Primer Assays for human OR6A2, TNF, IL-6, NOS2 and GAPDH. The results were calculated applying the 2^−ΔΔCTmethod³²using Gapdh/GAPDH as housekeeping gene.

OR6A2 Silencing in hMDMs

Human MDM cells (2×10⁶) were resuspended in 100 μl RT Nucleofector® Solution A mixture (Amaxa® Cell Line Nucleofector® Kit V; Lonza) containing 5 pmol non-silencing siRNA duplex (siCtrl, Thermo Fischer ientific) or silencing siRNA duplex targeted against the OR6A2 gene (assay ID 148343, Thermo Fischer Scientific). The suspension was transferred to an aluminum electroporation cuvette (Lonza) and pulsed in a Nucleofector 2b Device using (Lonza) using the premade BMDMs program. After electroporation, cells were transferred to RPMI-1640 medium supplemented with 20% of fetal calf serum, 100 U/mL penicillin and 100 μg/mL streptomycin, and 50 ng/mL rhMCSF (Peprotech) and cultured in 48-well plates at 37° C. and 5% CO₂for 48 h. Cell viability was determined by a trypan blue exclusion assay. Cells were further treated in culture medium for 12 h at 37° C. and 5% CO₂with Oct, (10 μM), LPS (500 ng/mL) alone or combined with Oct (LPS+Oct), and DMSO (0.1%) as a control and subsequently lysed in Qiazol (500 μl) for RNA purification. OR6A2, TNF, HA and NOS2 expression levels were analyzed by Real Time PCR as described before.

Flow Cytometric Analysis

BMDMs, hMDMs, mouse blood leukocytes and whole mount aortas were incubated in culture medium with Oct, (10 μM), LPS, (500 ng/mL) alone or combined (LPS+Oct) for 12h at 37° C. and 5% CO₂. After the incubation aortas were cut into small pieces and digested for cell suspension as previously described¹⁸.

Subsequently, aortic cell suspensions, BMDMs, blood leukocytes and hMDMs were incubated for 1 h with mouse or human Fc block solution, respectively, and stained with primary antibodies detecting Olfr2 (1:500, Thermo Fischer Scientific) or OR6A2 (1:500, Sigma Aldrich) for 1 h at RT. Normal rabbit IgG (1:500 Sigma Aldrich) incubated cells were used as a control.

All cells were then washed 3 times and incubated with an AlexaFluor488-conjugated goat anti-rabbit IgG secondary antibody (1:500, Thermo Fischer Scientific) for 30 min at RT. After 3 washing steps with PBS, BMDMs were stained in the dark for 20 min at RT with LIVE/DEAD (LD) Yellow fixable dye (Invitrogen) and F4/80-BV421. Aortic cells were stained in the dark for 20 min at RT with a mixture of CD45-PerCP, CD11b-PECy7, CD11c-BV605, TCRβ-BV711, CD4-PE-AlexaFluor610, CD19-APCCy7, GR1-BV786, F4/80-BV421 (Biolegend) antibodies and LD Yellow fixable dye. Mouse blood leukocytes were stained in the dark for 20 min at RT with a mixture of CD45-PerCP, CD115-PECy7, Ly6C-BV421, TCRβ-BV711, CD4-PE-AlexaFluor610, CD19-APCCy7, (Biolegend) antibodies and LD Yellow fixable dye. hMDMs were stained in the dark for 20 min at RT with LD Yellow fixable dye and anti-human CD45-AF700.

Samples were analyzed with the LSR-II flow cytometer (BD Biosciences). Data was acquired with the FACSDiva software (BD Biosciences) and analyzed with FlowJo software (Treestar Inc).

Intracellular Staining

Whole aortas and mouse blood leukocytes were incubated in culture medium with Oct, (10 μM), LPS, (500 ng/mL) alone or combined (LPS+Oct) for 12h at 37° C. and 5% CO₂. The protein transport inhibitor cocktail 1× (eBioscience) was added for whole 12h in the whole aorta samples and for the last 6 hours in the mouse blood leukocyte samples. Aortic cell suspensions were obtained as mentioned above, stained with CD45-PerCP, CD11b-PECy7, CD11c-BV605, TCRβ-BV711, CD4-PE-AlexaFluor610, CD19-APCCy7, GR1-BV786, F4/80-BV421 and LD Yellow fixable dye (Invitrogen). Blood leukocytes were stained with CD45-PerCP, CD115-PECy7, Ly6C-BV421, TCRβ−/CD4/CD19-APCCy7 (dump channel), and LD Yellow fixable dye.

Cells were then washed, fixed, permeabilized applying the Intracellular Fixation and Permeabilization Buffer Set (eBioscience), and stained with mouse anti-TNF-PE (eBioscience). Samples were analyzed with LSR-II (BD Biosciences). Data was acquired with FACSDiva software (BD Biosciences) and analyzed with FlowJo software (Treestar Inc).

IL-1β Production

Mouse BMDMs and human MDMs were pretreated with LPS (50 ng/mL) or left untreated for 18 h at 37° C. and 5% CO₂. After this period LPS pretreated and untreated cells were further incubated with Oct (10 μM) and Cit (100 μM) alone (LPS+Oct; LPS+Cit; Oct; Cit, respectively) or combined (LPS+Oct+Cit) for further 8 h. Supernatants were collected by centrifugation at 2000 g for 15 minutes at 4° C., collected and frozen at −80° C. until further IL-1β analysis by CBA (BD Biosciences).

Secreted Cytokines

Supernatants of stimulated cells and aortic tissue were analyzed by BD CBA Flex Sets (BD Biosciences) for mouse TNFα, CCL2, CCL4, IL-1β, or human TNF, IL6, and IL-1β according to the manufacturer's protocol. Samples were analyzed with LSR-II (BD Biosciences). Data was acquired with FACSDiva software (BD Biosciences) and analyzed with FCAP array software 3.0 (BD Biosciences).

Calcium Signalling

Aortic cell suspensions obtained as previously described¹⁸were pre-incubated with extracellular markers for vascular macrophages including CD45-PerCP, TCRβ/CD4-APCCy7 (Dump Channel), F4/80-BV421 and LD Yellow fixable dye (Invitrogen) for 20 min in Fc block solution at RT in the dark. Aortic cell suspensions were than washed twice and loaded with 2 μM of Fluo4 dye (Thermo Fischer Scientific) for 30 min at 37° C.

Subsequently, cells were washed and resuspended in 37° C. warm HBSS buffer containing Ca²⁺ and Mg²⁺ and acquired with the LSRII flow cytometer. After 60 seconds, Oct (10 μM), Cit (100 μM) or vehicle (DMSO 0.1%) was added and acquisition continued for additional 140 seconds. Data was acquired with FACSDiva software (BD Biosciences) and analyzed with FlowJo software (Treestar Inc). Mean fluorescence intensity of Fluo4 was integrated over 25 seconds form the start of the acquisition (tot. 8 intervals).

Immunoblotting

For Olfr2 protein detection in BMDMs, cells were incubated in culture medium with Oct, (10 μM), LPS, (500 ng/mL) alone or combined (LPS+Oct) for 12h at 37° C. and 5% CO₂. Cells were then washed and lysed in RIPA buffer containing protease inhibitors. Total protein content was quantified using DC Protein Assay (Bio-Rad) and solubilized in a volume ratio of 1:1 with Laemmli Buffer (Bio-Rad). SDS-Page analysis was conducted by heating the samples to 95° C. for 10 min and resolved on 12% Mini-PROTEAN TGX gels (Bio-Rad) under denaturing conditions. Pre-stained protein molecular weight standards (Thermo Fischer Scientific) were used as markers. Proteins were transferred onto Nitrocellulose membranes (Amersham Protran 0.2 μm NC) using the Mini Trans-blot electrophoretic transfer cell (Bio-Rad). Membranes were blocked in 5% bovine serum albumin (Sigma) prepared in tris-buffered saline with 0.1% Tween-20 (TBST). Membranes were incubated overnight at 4° C. with 1:1000 diluted Olfr2 (Thermo Fischer Scientific) or tubulin (CST) primary antibodies. Membranes were washed thrice with TBST and incubated with a HRP-conjugated secondary antibody (Promega) for 1 h at RT. Blots were again washed thrice with TBST and developed using a chemiluminescent substrate (Thermo Fischer Scientific). Protein bands were visualized with the ChemiDoc MP Imaging System (Bio-Rad) using Image Lab software.

Microarray Analysis and Dataset Comparison.

Published microarray datasets (Affymetrix mouse gene 1.0 ST array type) were used for the Olfr comparison: GSE68968 Vascular Mc); GSE77104 BMDMs, GSE43075 intra-peritoneal (IP) Mc); GSE100393 Small Intestine (SI) Mc); GSE15907 Lung Mc); GSE15907 Spleen (Red pulp) Mc); GSE15907 Microglia; GSE100393 SI DCs; GSE15907 Lung DCs; GSE15907 Mesenteric LN (MLN) DCs; GSE15907 Blood classical (CM) and non-classical monocyte (NCM) subpopulations. Affymetrix gene chip data were normalized using the robust multi-array average (RMA) method (log 2, background-corrected, quantile normalized). Correlation analyses were based on Pearson's correlation. Gene expression among dataset were normalized based on Gapdh expression (Xmax) using the ranking strategy: X−Xmin/Xmax−Xmin. Heatmap analysis and visualization was performed applying Morpheus, software.broadinstitute.org/morpheus.

RNAseq Analysis

For bulk RNA-seq, living CD45⁺, TCRβ⁻, CD19⁻, F4/80⁺ macrophages from aortas of Apoe^−/− mice fed a WD for 20 weeks were FACS-sorted with the FACSAriaIII (BD Biosciences).

Sequencing libraries were prepared from purified RNA using the RNeasy Mini Kit (Qiagen).

Double stranded (ds)-cDNA was prepared using the SMART-seq v4 Ultra Low RNA Kit for Illumina Sequencing (Takara-Clontech) according to the manufacturer's instructions. cDNA was amplified using 11 cycles and eluted in 12 μL. 5 μL of resulting cDNA was processed using a NexteraXT kit (Illumina, Calif., USA) following manufacturer's instructions. Samples were pooled into two batches, loaded on an Illumina HiSeq4000 and sequenced with 50 base pair single end reads (SR50). Transcriptomes were mapped to the mm10 mouse genome. Post-mapping quality control checks were used to exclude poor quality samples.

Immunofluorescence and Whole Mount Aorta Imaging

BMDMs and hMDMs were cultured on μ-Slide 8 well glass bottom (Ibidi) and treated as described above. Subsequent to incubation, cells were fixed with 2% paraformaldehyde (PFA) for 30 min at 37° C. and incubated with 5% BSA for 30 min at RT. BMDMs and hMDMs were than stained with Olfr2 and OR6A2 primary antibodies [1:500, Thermo Fischer Scientific (mouse Olfr2) and 1:500 Sigma-Aldrich Co (human OR6A2)], respectively, for 1 h in Fc blocking solution. Cells were then washed 5 times for 5 minutes with cold PBS and stained with secondary anti-rabbit IgG-AF488 (1:400, Thermo Fischer Scientific) for 30 min at 4° C. Nuclear counterstaining with Hoechst (1:2500, Sigma) was performed for 10 min Cells were then washed 5 times and imaged with a Zeiss LSM880 confocal scanning microscope. Image acquisition settings were adjusted with control samples (unstained sample, and isotypes control) and kept throughout the experiment.

For whole mount imaging, aortae form Apoe^−/− mice fed WD for 2 weeks were carefully cleaned in situ and fixed in 4% paraformaldehyde at 4° C. for 24 h. Subsequently, aortae were washed with PBS and transferred to 5 mL incubation buffer (2% FCS, 0.5% saponin, 0.1% sodium azide) containing Olfr2 primary antibody (1:1000, Thermo Fischer Scientific) for and agitated for 24 h at 37° C. Aortas were then washed 5 times with PBS and stained while agitation in 5 mL incubation buffer containing secondary anti-rabbit IgG-AF555 (1:500, Thermo Fischer Scientific), anti-mouse CD68-AF647 (1:200, Biolegend) and Hoechst (1:10000, Sigma) for 24 h at 37° C. Stained aortas were washed with PBS, opened longitudinally, mounted between glass slides, and imaged form the adventitial side with a Zeiss LSM880 confocal scanning microscope. Image acquisition settings were set with control samples (Unstained samples, CD68-AF647 FMO, and secondary anti-rabbit IgG-AF555 FMO) and maintained throughout the experiment. Image and scan processing were performed with Zen microscope software (Zeiss) and Imaris analysis software (Bitplane).

Plasma Octanal Quantification

Mouse blood plasma was collected reto-orbitally from 8-10 weeks old Apoe^−/− and WT mice fed WD or chow diet for 1 day.

Plasma octanal was derivatized with 3-nitrophenylhydrazine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and detected by LC/MS/MS after injection onto a Titan™ C18 UHPLC Column (1.9 μm particle size, 10 cm×2.1 mm, Supelco) with elution solvent generated by two pumps from solvent A, water+0.01% formic acid and B, acetonitrile+0.01% formic acid. A typical ion extracted LC chromatogram of octanal derivative in positive MRM mode with parent to daughter transition, m/z 264.2→119.1 was provided. [²H₁₆]octanal was spiked to plasma before derivatization reaction as internal standard and monitored in positive MRM mode with parent to daughter transition, m/z 280.2→120.2. Series concentrations of Oct were mixed with fixed amount of [²H₁₆]octanal followed by derivatization reaction were used to prepare calibration curve.

Statistics

All statistics in this study were performed using Graphpad Prism 6.0.

Analysis were done with ordinary one-way ANOVA followed by Tukey's test for multiple comparisons or the non-parametric Kruskal-Wallis test with Dunn's test for multiple comparisons. Where appropriate, statistical significance was tested with unpaired t-Test. The respective statistical tests are indicated in each figure legend. Data are presented as mean±SEM. P-values below 0.05 were considered significant.

Example 4: Identification of OLFRs that Modulate Immune Responses

An analysis on representative pro inflammatory genes (Ccl2, Ccl4 and Tnf) was performed (FIG. 14). Briefly, explanted aortas of Apoe^−/− mice kept in WD (2 wks), were treated for 12h with LPS (500 ng/mL) and different odorants (10 μM) or left untreated. Relative expression of Ccl2, Ccl4, and Tnf was quantified by real time PCR analysis and normalized to Gapdh expression and untreated control applying the 2-ΔΔCT method. N=3 per group.

Legend for odorants screened: Coumarin (Coum), Lilial (LIL), b-ionone (b-iono), Eugenol (EU), Butyric Acid (BA), Caramel Furanone (CF), Eugenol acetate (EA), Sandalwood (SW), Ethil Vanillin (EV), Ethil Fencol (EF), Androstadienone (AD), Androstenone (AT), Isovaleric Acid (IA), N-Amil Acetate (NA), Propyl propionate (PP), Octanal (OCT).

A statistical analysis of the representative pro inflammatory genes (Ccl2, Ccl4 and Tnf) was then performed (FIG. 15). The average relative expression for Ccl2, Ccl4, and Tnf was quantified by real time PCR analysis and normalized to Gapdh expression and untreated control applying the 2-ΔΔCT method. N=3 per group. p calculated by unpaired T Test. A p value<0.05 is considered significant. This analysis led to the identification of olfactory receptors for which the modulation of the expression or activity of one or more of these olfactory receptors, without being bound to a particular theory, results in modulation of an immune response corresponding to the embodiments provided herein. By way of example, and not by way of limitation, these olfactory receptors may include those olfactory receptors listed in Table 7 or one or more of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, or OR6A2 or an ortholog, homologue, variant or derivative thereof.

Example 5: Plasma Proteome Analysis

In this example, significantly modulated proteins in plasma from octanal treated mice (FIG. 16) and citral treated mice (FIG. 17) were examined Briefly, EDTA plasma samples were collected from octanal treated, citral treated, and vehicle treated mice at the end of the 8 weeks and analysis of 92 proteins therein were examined. The analysis of the 92 proteins comprising the Olink Mouse exploratory panel (https://www.olink.com/products/mouse-exploratory/) was performed using PEA (Proximity Extension Assay) technology. The PEA technique allows simultaneous assessment of proteins using oligonucleotide-labeled antibody probe pairs that bind to each protein within the sample. The PEA technique also permits accurate assessment of protein levels with repeated measurements by requiring both dual recognition of correctly matched antibody pairs and DNA-barcoding from sequence-specific oligonucleotides to generate a signal (PLoS ONE. 2014; 9(4)). The assay measures fold change in log 2 units. For this analysis, the raw data are converted into a t-statistic which can be compared across assays. Data are presented as means±SEM. P value<0.05 calculated by unpaired t-test. This analysis confirmed that modulation of olfactory receptor expression or activity may increase or decrease the expression or activity of proteins involved with immune response, and as such increasing or decreasing expression or activity of olfactory receptors may be utilized to increase or decrease expression or activity of certain immune response-related proteins. By way of example, and not by way of limitation, immune response-related proteins may include those genes listed in FIG. 16 and/or FIG. 17, or one or more of CCL5 (C-C Motif Chemokine Ligand 5), Tnfrsf12a (Osteoprotegerin), Axin 1, Nadk, Ahr (Aryl hydrocarbon receptor), QDPR (quinoid dihydropteridine reductase), HGF (Hepatocyte Growth Factor), ADAM23, or Snap29.

Example 6: Plasma Proteome Analysis

There are different sources of OLFR ligands, including diet, bacterial microbiota metabolism of various precursors (including from diet), and naturally occurring octanal in the subject. The role of gut microbiota in the production of ligands is demonstrated by generation of mice lacking gut microbiota which are found to have less concentrations of OLFR ligands than wild-type mice. For example, mice lacking gut microbiota are found to have 3-fold less concentration of octanal than wild-type mice (FIG. 18).

Example 7: Role of OLFRs in Immune Modulation

In order to determine an olfactory receptors' role in immune modulation, an Olfr knockout mouse is prepared. These mice are treated with a ligand or agonist of the OLFR and show reduced atherosclerosis when compared to Apoe−/− mice and WT mice also treated with the ligand or agonist. In one example, an Olfr2 knockout mouse is prepared and treated with octanal. These mice show reduced atherosclerosis when compared to Apoe−/− mice and WT mice also treated with octanal. As such, reduction of Olfr2 expression or activity reduces or inhibits inflammatory response.

To further define the role of olfactory receptors in modulating immune response, olfactory receptor involvement in inflammasome activation/signaling is demonstrated. For example, Olfr2 binding to its ligand represents a Signal 2 or activation signal, promoting the maturation and secretion of pro-inflammatory cytokines interleukin 1-beta (IL-1B) and interleukin 18 (IL-18). Without being bound to any particular theory, olfactory receptor activation may result in the activation of nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors (NLRs) in the inflammasome. By way of example, and not by way of limitation, NLRs, including NALP3 (NACHT, LRR and PYD domains-containing protein 3, also known as cryopyrin) or NLRC4 (NLR family CARD domain-containing protein 4) are activated by OLFR2.

REFERENCES

The references cited throughout this application are listed below. Each reference is incorporated by reference in their entirety.

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EXEMPLARY EMBODIMENTS

- 1. A method of modulating an immune response in a subject, comprising modulating expression or activity of one or more olfactory receptors (OLFR).
- 2. The method of embodiment 1, wherein the OLFR is expressed by a cell in vivo.
- 3. The method of embodiment 2, wherein the cell is an animal cell, with the proviso that the cell is not an olfactory cell.
- 4. The method of any one of embodiments 1-3, wherein the cell is a macrophage.
- 5. The method of claim 4, wherein the macrophage is a vascular macrophage.
- 6. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of inhibiting, decreasing, reducing, suppressing, limiting or controlling the immune response by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.
- 7. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.
- 8. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an autoimmune response, disorder or disease in a subject, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.
- 9. The method of embodiment 8, wherein the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation, or an adverse symptom of the autoimmune response, disorder or disease in the subject.
- 10. The method of embodiment 9, wherein the adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or an adverse symptom of the autoimmune response, disorder or disease is swelling, pain, rash, headache, fever, nausea, diarrhea, bloat, lethargy, skeletal joint stiffness or tissue or cell damage.
- 11. The method of embodiment 9 or 10, wherein the adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response or inflammation or the adverse symptom of the autoimmune response, disorder or disease is chronic or acute.
- 12. The method of any one of embodiments 8 to 11, wherein the immune disorder, inflammatory response, inflammation, autoimmune response disorder or autoimmune disease comprises rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common g chain (c) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (g5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon g receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1 A/SAP deficiency), or hyper IgE syndrome.
- 13. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse cardiovascular event or cardiovascular disease by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.
- 14. The method of embodiment 13, wherein the adverse cardiovascular event or cardiovascular disease comprises coronary artery disease, peripheral artery disease, cerebrovascular disease, renal artery disease, stroke, myocardial infarction (heart attack), ischemic heart failure, transient ischemic attack or brain trauma, atherosclerosis, atherosclerotic plaque formation or elevated blood cholesterol.
- 15. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of decreasing, reducing, inhibiting, suppressing, limiting or controlling atherosclerosis, by a method comprising administering to the subject an effective amount of an agent that inhibits the expression of or deactivates the OLFR.
- 16. The method of any one of embodiments 1-5, wherein the method comprises one or more of reducing or inhibiting in a subject viral, bacterial or fungal infection, by a method comprising administering to the subject an effective amount of an agent that increases the expression of or activates the OLFR.
- 17. The method of any one of embodiments 1-5, wherein the modulation comprises one or more of comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling an adverse symptom of the neoplasia, neoplastic disorder, tumor, cancer or malignancy, metastasis of a neoplasia, tumor, cancer or malignancy to other sites, or formation or establishment of a metastatic neoplasia, neoplastic disorder, tumor, cancer or malignancy to other sites distal from a primary neoplasia, neoplastic disorder, tumor, cancer or malignancy, or viral, bacterial or fungal infection by a method comprising administering to the subject an effective amount of an agent that increases the expression of or activates the OLFR.
- 18. The method of embodiment 17, wherein the neoplasia, neoplastic disorder, tumor, cancer or malignancy treated is a carcinoma, sarcoma, neuroblastoma, cervical cancer, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma or melanoma; or a lung, thyroid, head or neck, nasopharynx, throat, nose or sinuses, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, gastrointestinal (mouth, esophagus, stomach, duodenum, ileum, jejunum (small intestine), colon, rectum), genito-urinary tract (uterus, ovary, cervix, endometrial, bladder, testicle, penis, prostate), kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin neoplasia, neoplastic disorder, tumor, cancer or malignancy.
- 19. The method of any one of embodiments 1-18, wherein the OLFR is an OLFR listed in any one of Tables 1-9, and FIGS. 2A and 2B.
- 20. The method of any one of embodiments 1-18, wherein the OLFR is an OLFR listed in Table 7.
- 21. The method of any one of embodiments 1-18, wherein the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.
- 22. The method of any one of embodiments 6 to 21, wherein the agent is selected from the group of: a ligand or small molecule that binds to the OLFR or blocks the binding of the OLFR to the ligand or an agent that inhibits the expression of the OLFR by the cell.
- 23. The method of any preceding claim, wherein the agent is selected from the group of an antibody, fragment or mimetic that binds to OLFR or an OLFR ligand, an anti-OLFR gene silencing agent, octanal, heptanal, or a prodrug or solvate thereof.
- 24. The method of any one of embodiments 6-21, wherein the agent modulates the OLFR by modulating the trafficking of the OLFR to a plasma membrane of a cell.
- 25. The method of embodiment 24, wherein the agent is a protein selected from the group of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), or guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 26. The method of embodiment 24, wherein the agent is a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 27. The method of any of embodiments 16-26, wherein the immune response is stimulated by a method comprising administering an agent that increases expression or secretion of an inflammatory cytokine.
- 28. The method of embodiment 28, wherein the inflammatory cytokine is selected from the group consisting of tumor necrosis factor (TNF), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, interleukin 6 (IL-6), IL-1B, IL-18, and nitric oxide synthase 2 (NOS2).
- 29. A method of suppressing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR), thereby suppressing an immune response in the subject.
- 30. The method of embodiment 29, wherein the OLFR is an OLFR listed in any one of Tables 1-9.
- 31. The method of embodiment 29 or 30, wherein the OLFR is an OLFR listed in Table 7.
- 32. The method of any of embodiments 29-31, wherein the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.
- 33. The method of any of embodiments 29-32, wherein the agent is a gene silencing agent.
- 34. The method of embodiment 23 or 33, wherein the gene silencing agent is selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme.
- 35. The method of embodiment 34, wherein the RNAi molecule is selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA).
- 36. The method of any of embodiments 29-32, wherein the agent decreases the activity of the OLFR by inhibiting the binding of the OLFR with its ligand.
- 37. The method of embodiment 36, wherein the ligand is an OLFR ligand listed in Table 8.
- 38. The method of any of embodiments 29-32, wherein the agent is an OLFR antagonist.
- 39. The method of embodiment 38, wherein the OLFR antagonist is citral, undecanal, oxyphenylon, phenirat, methyl cinnamaldehyde, hydrocinamaldehyde, bourgeonal, ethylhexanoic acid, α-ionone, octanoic acid, a solvate or prodrug thereof. 40. The method of embodiment 38, wherein the OLFR antagonist is an antagonist listed in Table 9.
- 41. The method of any of embodiments 29-32, wherein the agent decreases the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.
- 42. The method of any of embodiments 29-32, wherein the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.
- 43. A method of increasing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby increasing an immune response in the subject.
- 44. A method of suppressing an immune response in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell, thereby suppressing an immune response in the subject.
- 45. A method of treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR).
- 46. A method of treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.
- 47. A method of treating a cardiovascular disease in a subject in need thereof, the method comprising administering to the subject an agent that decreases the expression of or activity of an olfactory receptor (OLFR).
- 48. A method of a cardiovascular disease in a subject in need thereof, the method comprising administering to the subject an agent that inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.
- 49. A method of treating an infection in a subject in need thereof, the method comprising administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR).
- 50. A method of treating an infection in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.
- 51. The method of embodiment 49 or 50, wherein the infection is selected from the group consisting of a viral infection, bacterial infection, or fungal infection.
- 52. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an agent that increases the expression of or activates an olfactory receptor (OLFR).
- 53. A method of cancer in a subject in need thereof, the method comprising administering to the subject an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.
- 54. A method of modulating the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that modulates the expression or activity of an olfactory receptor (OLFR).
- 55. The method of embodiment 54, wherein the agent increases the expression of or activates the OLFR.
- 56. The method of embodiment 54, wherein the agent decreases the expression or activity of the OLFR.
- 57. A method of increasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that increases the expression of or activates an olfactory receptor (OLFR).
- 58. A method of decreasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that decreases the expression of or inhibits an olfactory receptor (OLFR).
- 59. A method of modulating the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that modulates the trafficking of an olfactory receptor (OLFR) to a plasma membrane of the cell.
- 60. The method of embodiment 59, wherein agent increases or promotes the trafficking of the OLFR to the plasma membrane of the cell.
- 61. The method of embodiment 59, wherein the agent decreases or inhibits the trafficking of the OLFR to the plasma membrane of a cell.
- 62. A method of increasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that increases or promotes the trafficking of an olfactory receptor (OLFR) to a plasma membrane of the cell.
- 63. A method of decreasing the expression or activity of one or more proteins involved in an immune response, the method comprising contacting a cell with an agent that decreases or inhibits the trafficking of an olfactory receptor (OLFR) to a plasma membrane of a cell.
- 64. The method of any of embodiments 44-48, 54, 56, 58, 59, 61, and 63, wherein the agent is a gene silencing agent.
- 65. The method of embodiment 64, wherein the gene silencing agent is selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme.
- 66. The method of embodiment 65, wherein the RNAi molecule is selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA).
- 67. The method of any of embodiments 45, 47, 56, and 58, wherein the agent decreases the activity of the OLFR by inhibiting the binding of the OLFR with its ligand.
- 68. The method of embodiment 67, wherein the ligand is an OLFR ligand listed in Table 8.
- 69. The method of any of embodiments 44-48, 54, 56, 58, 59, 61, and 63, wherein the agent is an OLFR antagonist.
- 70. The method of embodiment 69, wherein the OLFR antagonist is citral, undecanal, oxyphenylon, phenirat, methyl cinnamaldehyde, hydrocinamaldehyde, bourgeonal, ethylhexanoic acid, α-ionone, octanoic acid, a solvate or prodrug thereof. 71. The method of embodiment 69, wherein the OLFR antagonist is an antagonist listed in Table 9.
- 72. The method of any of embodiments 45, 47, 56, and 58, wherein the agent decreases the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.
- 73. The method of any of embodiments 44-48, 54, 56, 58, 59, 61, and 63, wherein the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.
- 74. The method of any of embodiments 43, 49-55, 57, 59, and 60, wherein the agent is an OLFR agonist.
- 75. The method of embodiment 74, wherein the OLFR agonist is an agonist listed in Table 8.
- 76. The method of embodiment 74, wherein the OLFR agonist is selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, decyl aldehyde.
- 77. The method of any of embodiments 43, 49-55, 57, 59, and 60, wherein the agent is octanal, heptanal, or a prodrug or solvate thereof.
- 78. The method of any of embodiments 43, 49-55, 57, 59, and 60, wherein the agent is a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 79. The method of any of embodiments 43, 49-55, 57, 59, and 60, wherein the agent comprises a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 80. The method of any of embodiments 43-79, wherein the OLFR is an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B.
- 81. The method of any of embodiments 43-80, wherein the OLFR is an OLFR listed in Table 7.
- 82. The method of any of embodiments 43-81, wherein the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.
- 83. The method of any of embodiments 43-82, wherein the OLFR is expressed by a cell in vivo.
- 84. The method of embodiment 83, wherein the cell is an animal cell, with the proviso that the cell is not an olfactory cell.
- 85. The method of embodiment 83 or 84, wherein the cell is a macrophage. 86. The method of claim 85, wherein the macrophage is a vascular macrophage. 87. The method of any one of embodiments 54-63, wherein the one or more proteins involved in an immune response is any of the proteins shown in FIGS. 16 and 17.
- 88. The method of any one of embodiments 54-63, wherein the one or more proteins involved in an immune response is a protein selected from CCL5 (C-C Motif Chemokine Ligand 5), Tnfrsf12a (Osteoprotegerin), Axin 1, Nadk, Ahr (Aryl hydrocarbon receptor), QDPR (quinoid dihydropteridine reductase), HGF (Hepatocyte Growth Factor), ADAM23, or Snap29.
- 89. The method of any of embodiments 6 to 53, wherein the administration is local or systemic.
- 90. The method of embodiment 89, wherein the administration comprises by a method comprising intravenously.
- 91. The method of any one of embodiments 6 to 53, 89, and 90, wherein the subject is a mammal.
- 92. The method of any one of embodiments 6 to 53, and 89-91, wherein the subject has or is predisposed to a disease or disorder involving an immune dysregulation.
- 93. The method of embodiment 91 or 92, wherein the subject is a human patient.
- 94. A kit comprising an agent that modulates the activity of an OLFR and instructions for use.
- 95. The kit of any embodiment 94, wherein the agent is a gene silencing agent.
- 96. The kit of embodiment 95, wherein the gene silencing agent is selected from the group consisting of a RNA interference (RNAi) molecule, zinc finger nuclease, transcription activator-like effector nuclease (TALEN), and Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) enzyme.
- 97. The kit of embodiment 96, wherein the RNAi molecule is selected from the group consisting of a small interference RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA).
- 98. The kit of any of embodiments 94-97, wherein the agent modulates the activity of the OLFR by inhibiting the binding of the OLFR with its ligand.
- 99. The kit of embodiment 98, wherein the ligand is an OLFR ligand listed in Table 8.
- 100. The kit of embodiment 94, wherein the agent is an OLFR antagonist.
- 101. The kit of embodiment 100, wherein the OLFR antagonist is citral, undecanal, oxyphenylon, phenirat, methyl cinnamaldehyde, hydrocinamaldehyde, bourgeonal, ethylhexanoic acid, α-ionone, octanoic acid, a solvate or prodrug thereof.
- 102. The kit of embodiment 100, wherein the OLFR antagonist is an antagonist listed in Table 9.
- 103. The kit of embodiment 94, wherein the agent modulates the activity of the OLFR by inhibiting the trafficking of the OLFR to a plasma membrane of a cell.
- 104. The kit of embodiment 94, wherein the agent is an antibody, fragment or mimetic thereof that binds to an OLFR.
- 105. The kit of embodiment 94, wherein the agent is an OLFR agonist.
- 106. The kit of embodiment 105, wherein the OLFR agonist is an agonist listed in Table 8.
- 107. The kit of embodiment 105, wherein the OLFR agonist is selected from the group consisting of octanal, coumarin, helional, lilial, b-ionone, androstenone, androstadienone, caramel furanone, 3-phenyl propyl propionate, eugenol, ethil vanillin, 2-ethyl-fencol, isovaleric acid, nonanoic acid, butyl butyryllactate, butyric acid, isovaleric acid, propionic acid, N-amyl acetate, eugenol acetate, sandalwood, S-(−)-citronellol, S-(−)-citronellal, (+)-carvine, (−) carvone, (+) carvone, linalool, bourgeonal, acetophenone, amyl butyrate, nonanethiol, allyl phenyl acetate, N-amyl acetate, muscone, isoeugenol, eugenol methyl ether, 1-hexanol, 1-heptanole, 1-octanol, celery ketone, anis aldehyde, (+)-menthol, vanillin, guaiacol, lyral, ethyl heptanoate, methyl octanoate, nonanal 1-nonanol, 2-nonanol, 3-octanone, 3-nonanone, decyl aldehyde. 108. The kit of embodiment 94, wherein the agent is octanal, heptanal, or a prodrug or solvate thereof.
- 109. The kit of embodiment 94, wherein the agent is a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 110. The kit of embodiment 94, wherein the agent comprises a nucleotide encoding a protein selected from the group consisting of receptor transporting protein 1 (RTP1), RTP2, receptor expression enhancing protein 1 (REEP1), aminoacylase 3 (Acy3), and guanine nucleotide-binding protein G(olf) subunit alpha (Gnal).
- 111. The kit of any of embodiments 94-110, wherein the OLFR is an OLFR listed in any one of Tables 1-9 and FIGS. 2A-2B.
- 112. The kit of any of embodiments 94-111, wherein the OLFR is an OLFR listed in Table 7.
- 113. The kit of any of embodiments 94-112, wherein the OLFR is selected from the group consisting of OR7C1, OR7D4, OR10A6, OR11H6, OR4E2, OR10H1, and OR6A2.

TABLE 1

Olfactory receptors and accessory genes GAPDH ranked

expression as displayed in the heatmap of FIG. 1

Aortic
Aortic
BMDM
BMDM

IP

MLN
Lung

Mφ
Mφ
Mφ −
Mφ
SI
SI
Mφ
IP
DCs
DCs

Naive
LPS
M0
LPS
DCs
Mφ
LPS
Mφ
CD8+
103+

Gapdh
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

Rtp1
0.35
0.33
0.30
0.30
0.28
0.30
0.28
0.25
0.32
0.29

Rtp2
0.39
0.41
0.33
0.38
0.38
0.37
0.31
0.29
0.34
0.35

Reep3
0.894
0.921
0.694
0.765
0.599
0.718
0.603
0.675
0.616
0.678

Cnga1
0.16
0.163
0.136
0.162
0.149
0.169
0.123
0.109
0.133
0.107

Cnga2
0.169
0.156
0.142
0.169
0.201
0.199
0.156
0.138
0.185
0.169

Cnga3
0.291
0.286
0.249
0.254
0.273
0.297
0.235
0.216
0.295
0.253

Cnga4
0.235
0.206
0.23
0.245
0.232
0.249
0.213
0.181
0.256
0.225

Cngb1
0.914
0.929
0.314
0.31
0.393
0.412
0.26
0.256
0.27
0.247

Acy3
0.529
0.535
0.451
0.465
0.395
0.502
0.435
0.443
0.379
0.342

Gna1
0.24
0.24
0.23
0.22
0.29
0.26
0.15
0.16
0.17
0.17

Olfr1
0.23
0.25
0.22
0.25
0.23
0.22
0.21
0.20
0.23
0.20

Olfr10
0.47
0.48
0.23
0.25
0.24
0.27
0.21
0.19
0.22
0.22

Olfr100
0.28
0.26
0.18
0.16
0.14
0.14
0.16
0.14
0.19
0.15

Olfr1000
0.08
0.11
0.07
0.09
0.17
0.16
0.08
0.08
0.10
0.09

Olfr1002
0.02
0.02
0.04
0.06
0.05
0.06
0.07
0.05
0.04
0.03

Olfr1006
0.22
0.23
0.21
0.22
0.22
0.25
0.21
0.17
0.19
0.20

Olfr1008
0.12
0.17
0.13
0.14
0.17
0.18
0.08
0.08
0.13
0.10

Olfr1009
0.27
0.27
0.16
0.18
0.18
0.20
0.17
0.16
0.18
0.16

Olfr101
0.26
0.26
0.21
0.26
0.19
0.24
0.17
0.16
0.18
0.17

Olfr1010
0.33
0.31
0.21
0.23
0.25
0.26
0.21
0.19
0.25
0.19

Olfr1012
0.31
0.35
0.25
0.31
0.25
0.26
0.22
0.21
0.24
0.22

Olfr1013
0.08
0.11
0.09
0.12
0.12
0.12
0.09
0.09
0.06
0.06

Olfr1014
0.11
0.16
0.07
0.09
0.10
0.13
0.08
0.09
0.05
0.07

Olfr1015
0.26
0.30
0.22
0.26
0.24
0.27
0.20
0.20
0.21
0.18

Olfr1016
0.31
0.30
0.22
0.27
0.23
0.28
0.24
0.21
0.26
0.22

Olfr1018
0.16
0.15
0.14
0.16
0.18
0.19
0.15
0.14
0.16
0.14

Olfr1019
0.18
0.22
0.19
0.22
0.21
0.21
0.20
0.17
0.20
0.18

Olfr102
0.28
0.26
0.18
0.16
0.14
0.14
0.16
0.14
0.19
0.15

Olfr1020
0.10
0.15
0.10
0.09
0.10
0.09
0.09
0.07
0.06
0.05

Olfr1022
0.17
0.19
0.12
0.08
0.12
0.15
0.09
0.08
0.10
0.08

Olfr1023
0.13
0.17
0.13
0.14
0.13
0.15
0.12
0.10
0.13
0.10

Olfr1024
0.21
0.23
0.17
0.20
0.22
0.28
0.16
0.15
0.19
0.19

Olfr1026
0.12
0.11
0.12
0.12
0.14
0.15
0.11
0.09
0.11
0.10

Olfr1028
0.24
0.31
0.16
0.17
0.18
0.19
0.08
0.08
0.09
0.09

Olfr1029
0.58
0.59
0.24
0.25
0.26
0.27
0.15
0.18
0.19
0.14

Olfr103
0.22
0.20
0.17
0.20
0.15
0.15
0.15
0.12
0.15
0.15

Olfr1030
0.21
0.23
0.11
0.13
0.11
0.12
0.12
0.11
0.09
0.09

Olfr1031
0.12
0.13
0.11
0.11
0.08
0.09
0.08
0.09
0.07
0.07

Olfr1032
0.24
0.22
0.16
0.16
0.16
0.16
0.13
0.13
0.15
0.12

Olfr1033
0.07
0.09
0.06
0.06
0.04
0.07
0.03
0.05
0.03
0.03

Olfr1034
0.20
0.18
0.16
0.16
0.17
0.21
0.19
0.17
0.20
0.17

Olfr1036
0.20
0.18
0.16
0.16
0.17
0.21
0.19
0.17
0.20
0.17

Olfr1037
0.04
0.04
0.05
0.08
0.08
0.07
0.04
0.04
0.04
0.04

Olfr1038-ps
0.16
0.27
0.11
0.11
0.13
0.12
0.07
0.06
0.11
0.07

Olfr1039
0.05
0.02
0.02
0.04
0.02
0.04
NA
NA
0.02
0.02

Olfr1040
0.24
0.28
0.20
0.22
0.23
0.24
0.18
0.18
0.19
0.20

Olfr1042
0.30
0.31
0.32
0.36
0.30
0.36
0.24
0.24
0.24
0.23

Olfr1043
0.26
0.30
0.21
0.24
0.17
0.19
0.18
0.17
0.18
0.16

Olfr1044
0.12
0.14
0.14
0.15
0.14
0.15
0.14
0.12
0.10
0.09

Olfr1045
0.20
0.25
0.10
0.09
0.17
0.17
0.13
0.11
0.15
0.14

Olfr1046
0.02
0.03
0.03
0.06
0.03
0.06
0.03
0.01
0.02
0.01

Olfr1047
0.00
0.00
NA
NA
NA
0.01
NA
NA
0.01
0.00

Olfr1048
0.16
0.16
0.10
0.14
0.19
0.19
0.12
0.11
0.12
0.12

Olfr1049
NA
NA
0.04
0.05
0.08
0.02
0.00
NA
0.01
0.00

Olfr1051
NA
NA
NA
0.07
0.02
0.02
NA
NA
NA
NA

Olfr1052
0.07
0.08
0.11
0.09
0.11
0.12
0.08
0.06
0.10
0.08

Olfr1053
0.16
0.21
0.18
0.20
0.22
0.24
0.16
0.12
0.18
0.22

Olfr1054
0.24
0.28
0.17
0.18
0.23
0.21
0.15
0.14
0.16
0.18

Olfr1055
0.08
0.10
0.09
0.10
0.09
0.10
0.09
0.06
0.09
0.07

Olfr1056
0.17
0.22
0.11
0.13
0.18
0.17
0.15
0.12
0.15
0.15

Olfr1057
0.22
0.24
0.18
0.20
0.18
0.19
0.13
0.12
0.13
0.13

Olfr1058
0.12
0.18
0.10
0.10
0.10
0.12
0.08
0.07
0.07
0.06

Olfr106-ps
0.02
0.02
0.02
0.13
0.04
0.06
0.02
0.01
0.01
0.02

Olfr1061
NA
0.01
0.01
0.02
0.04
0.03
NA
0.00
NA
0.01

Olfr1062
0.17
0.16
0.13
0.18
0.16
0.19
0.16
0.14
0.14
0.16

Olfr1065
0.12
0.18
0.10
0.10
0.10
0.12
0.08
0.07
0.07
0.06

Olfr1066
0.07
0.10
0.02
0.04
0.04
0.03
0.01
0.00
NA
0.00

Olfr107
0.04
0.06
0.13
0.24
0.11
0.14
0.05
0.05
0.08
0.05

Olfr1076
0.36
0.39
0.09
0.14
0.14
0.18
0.06
0.06
0.07
0.05

Olfr1077-ps1
0.28
0.32
0.21
0.22
0.24
0.30
0.18
0.18
0.23
0.20

Olfr1079
0.09
0.13
0.06
0.09
0.10
0.08
0.05
0.05
0.09
0.05

Olfr108
0.12
0.16
0.10
0.27
0.12
0.09
0.05
0.07
0.07
0.05

Olfr1080
0.01
0.03
0.03
0.05
0.10
0.09
0.00
NA
0.02
NA

Olfr1082
0.02
0.06
NA
0.02
0.02
0.05
0.00
NA
NA
NA

Olfr1084
0.03
0.10
0.02
0.02
0.01
NA
NA
NA
NA
NA

Olfr1085
0.19
0.28
0.17
0.23
0.25
0.31
0.18
0.15
0.16
0.16

Olfr1086
0.27
0.24
0.26
0.29
0.25
0.28
0.21
0.20
0.22
0.21

Olfr1087
0.14
0.17
0.11
0.14
0.14
0.16
0.08
0.08
0.10
0.11

Olfr1089
0.17
0.18
0.12
0.16
0.12
0.13
0.12
0.09
0.11
0.08

Olfr109
0.31
0.28
0.27
0.48
0.24
0.25
0.26
0.25
0.27
0.25

Olfr1090
0.11
0.13
0.12
0.10
0.12
0.14
0.08
0.08
0.10
0.09

Olfr1093
0.20
0.20
0.21
0.20
0.22
0.23
0.16
0.15
0.19
0.16

Olfr1094
0.07
0.06
0.08
0.10
0.13
0.13
0.08
0.07
0.09
0.07

Olfr1095
0.00
0.02
0.01
0.12
0.04
0.10
0.04
0.02
0.05
0.03

Olfr1097
0.15
0.17
0.08
0.10
0.13
0.13
0.10
0.07
0.04
0.07

Olfr1098
0.09
0.12
0.10
0.09
0.09
0.12
0.08
0.07
0.05
0.06

Olfr1099
0.26
0.31
0.21
0.21
0.24
0.25
0.17
0.13
0.16
0.18

Olfr11
0.31
0.30
0.23
0.30
0.30
0.33
0.23
0.20
0.25
0.23

Olfr110
0.22
0.24
0.52
0.45
0.22
0.23
0.17
0.15
0.19
0.18

Olfr1100
0.10
0.12
0.05
0.11
0.09
0.12
0.03
0.03
0.04
0.02

Olfr1101
0.17
0.17
0.14
0.13
0.16
0.16
0.09
0.09
0.10
0.12

Olfr1102
0.04
0.07
0.03
0.03
0.04
0.05
0.03
0.02
NA
0.00

Olfr1104
0.24
0.24
0.16
0.17
0.16
0.19
0.13
0.12
0.14
0.14

Olfr1105
0.23
0.24
0.20
0.21
0.19
0.26
0.18
0.16
0.22
0.17

Olfr1106
0.17
0.16
0.10
0.10
0.11
0.11
0.12
0.11
0.11
0.08

Olfr1107
0.09
0.10
0.06
0.07
0.10
0.12
0.04
0.02
0.03
0.02

Olfr1109
0.08
0.10
0.06
0.10
0.12
0.12
0.06
0.05
0.07
0.04

Olfr111
0.26
0.27
0.72
0.68
0.18
0.23
0.20
0.21
0.14
0.14

Olfr1110
0.16
0.19
0.13
0.10
0.13
0.13
0.09
0.07
0.11
0.11

Olfr1111
0.20
0.20
0.15
0.16
0.18
0.15
0.12
0.10
0.13
0.11

Olfr1112
0.08
0.09
0.07
0.08
0.10
0.09
0.05
0.04
0.05
0.05

Olfr1113
0.21
0.27
0.15
0.16
0.15
0.17
0.10
0.10
0.12
0.10

Olfr1115
0.29
0.30
0.19
0.22
0.23
0.26
0.19
0.18
0.21
0.17

Olfr1116
0.08
0.16
0.05
0.05
0.07
0.06
0.04
0.04
0.02
0.00

Olfr1118
0.27
0.28
0.15
0.20
0.17
0.16
0.13
0.12
0.18
0.13

Olfr112
0.07
0.11
0.46
0.49
0.10
0.11
0.05
0.05
0.03
0.04

Olfr1120
0.21
0.21
0.13
0.16
0.16
0.14
0.13
0.13
0.14
0.12

Olfr1121
0.10
0.11
0.10
0.12
0.14
0.16
0.09
0.08
0.09
0.09

Olfr1122
0.25
0.25
0.21
0.24
0.24
0.28
0.17
0.16
0.19
0.17

Olfr1123
0.03
0.05
0.05
0.07
0.04
0.03
0.08
0.06
0.07
0.06

Olfr1124
0.13
0.15
0.02
0.06
0.07
0.09
0.02
0.03
0.01
NA

Olfr1126
0.30
0.33
0.16
0.25
0.20
0.22
0.18
0.17
0.20
0.18

Olfr1128
0.33
0.32
0.24
0.24
0.25
0.27
0.22
0.19
0.22
0.19

Olfr1129
0.14
0.18
0.09
0.13
0.11
0.10
0.09
0.09
0.08
0.08

Olfr113
0.40
0.42
0.49
0.54
0.27
0.26
0.21
0.21
0.21
0.18

Olfr1130
0.10
0.14
0.12
0.17
0.15
0.18
0.07
0.05
0.07
0.07

Olfr1131
0.18
0.18
0.11
0.13
0.15
0.15
0.13
0.12
0.11
0.09

Olfr1132
0.22
0.21
0.15
0.21
0.22
0.25
0.17
0.14
0.14
0.16

Olfr1133
0.31
0.31
0.21
0.27
0.27
0.29
0.18
0.17
0.21
0.19

Olfr1134
0.06
0.04
0.05
0.07
0.09
0.10
0.07
0.10
0.12
0.06

Olfr1135
0.08
0.12
0.06
0.14
0.16
0.19
0.07
0.06
0.05
0.04

Olfr1136
0.24
0.22
0.15
0.19
0.15
0.14
0.14
0.11
0.15
0.13

Olfr1137
0.28
0.29
0.19
0.18
0.23
0.22
0.16
0.14
0.15
0.15

Olfr1138
0.17
0.19
0.15
0.13
0.18
0.16
0.13
0.12
0.16
0.13

Olfr114
0.24
0.26
0.41
0.37
0.19
0.17
0.12
0.10
0.12
0.11

Olfr1140
0.18
0.23
0.10
0.11
0.14
0.17
0.10
0.10
0.11
0.12

Olfr1141
0.12
0.15
0.07
0.10
0.12
0.13
0.08
0.08
0.09
0.07

Olfr1143
0.12
0.16
0.08
0.09
0.11
0.13
0.09
0.07
0.08
0.07

Olfr1145
0.12
0.17
0.13
0.14
0.13
0.15
0.11
0.09
0.11
0.10

Olfr1148
0.42
0.44
0.31
0.31
0.37
0.37
0.40
0.40
0.27
0.31

Olfr115
0.24
0.25
0.35
0.35
0.23
0.23
0.23
0.21
0.21
0.19

Olfr1151
0.19
0.19
0.14
0.16
0.16
0.16
0.12
0.10
0.14
0.11

Olfr1152
0.48
0.49
0.37
0.42
0.44
0.50
0.32
0.33
0.37
0.31

Olfr1153
0.21
0.23
0.18
0.16
0.16
0.19
0.16
0.14
0.15
0.16

Olfr1154
0.17
0.17
0.11
0.14
0.14
0.13
0.09
0.08
0.12
0.09

Olfr1155
0.35
0.38
0.30
0.32
0.32
0.34
0.27
0.25
0.28
0.26

Olfr1156
0.28
0.25
0.22
0.27
0.24
0.27
0.18
0.18
0.22
0.20

Olfr1157
0.12
0.14
0.13
0.15
0.13
0.15
0.14
0.12
0.14
0.16

Olfr1158
0.19
0.21
0.10
0.14
0.13
0.13
0.13
0.12
0.09
0.11

Olfr116
0.12
0.16
0.15
0.18
0.10
0.11
0.09
0.08
0.10
0.09

Olfr1160
0.22
0.28
NA
0.03
0.02
0.01
0.03
0.01
NA
NA

Olfr1161
0.10
0.13
0.11
0.12
0.15
0.18
0.11
0.10
0.11
0.09

Olfr1162
0.26
0.29
0.22
0.23
0.26
0.27
0.26
0.24
0.25
0.21

Olfr1163
0.26
0.29
0.22
0.23
0.26
0.27
0.26
0.24
0.25
0.21

Olfr1164
0.09
0.08
0.10
0.11
0.16
0.18
0.08
0.08
0.08
0.08

Olfr1166
0.22
0.29
0.12
0.08
0.11
0.14
0.12
0.12
0.10
0.07

Olfr1167
0.06
0.11
0.01
0.05
0.05
0.08
0.06
0.02
0.01
0.01

Olfr1168
0.14
0.14
0.15
0.15
0.17
0.18
0.12
0.13
0.13
0.09

Olfr117
0.15
0.13
0.12
0.15
0.14
0.13
0.11
0.12
0.13
0.12

Olfr1170
0.13
0.15
0.10
0.12
0.12
0.14
0.15
0.12
0.08
0.09

Olfr1173
0.11
0.12
0.09
0.09
0.13
0.15
0.08
0.09
0.07
0.06

Olfr1174-ps
0.79
0.80
0.62
0.67
0.61
0.63
0.57
0.52
0.66
0.63

Olfr1176
0.09
0.09
0.07
0.11
0.11
0.13
0.09
0.07
0.06
0.07

Olfr1178
0.18
0.20
0.10
0.10
0.11
0.12
0.08
0.06
0.09
0.07

Olfr1179
0.28
0.27
0.22
0.21
0.21
0.27
0.16
0.18
0.18
0.16

Olfr118
0.15
0.15
0.14
0.18
0.21
0.24
0.11
0.11
0.15
0.15

Olfr1180
0.13
0.16
0.08
0.11
0.09
0.08
0.09
0.07
0.07
0.07

Olfr1181
0.30
0.31
0.05
0.07
0.12
0.13
0.04
0.04
0.04
0.02

Olfr1182
0.36
0.40
0.15
0.17
0.17
0.19
0.13
0.11
0.09
0.13

Olfr1183
0.11
0.20
0.05
0.07
0.10
0.08
0.03
0.01
0.02
0.02

Olfr1184
0.08
0.10
0.08
0.07
0.08
0.12
0.10
0.07
0.05
0.06

Olfr1186
0.07
0.07
0.03
0.07
0.04
0.06
0.05
0.05
0.05
0.03

Olfr1188
0.20
0.21
0.12
0.16
0.17
0.17
0.14
0.14
0.14
0.10

Olfr1189
0.10
0.10
0.07
0.11
0.16
0.16
0.08
0.07
0.06
0.06

Olfr119
0.19
0.21
0.12
0.13
0.23
0.20
0.08
0.06
0.14
0.11

Olfr1193
0.23
0.25
0.15
0.11
0.11
0.12
0.08
0.08
0.11
0.09

Olfr1195
0.06
0.04
0.04
0.08
0.10
0.11
0.05
0.03
0.04
0.04

Olfr1196
0.25
0.30
0.17
0.19
0.18
0.17
0.17
0.15
0.17
0.14

Olfr1197
0.25
0.30
0.17
0.19
0.18
0.17
0.17
0.15
0.17
0.14

Olfr1198
0.05
0.07
0.06
0.06
0.10
0.11
0.03
0.02
0.04
0.04

Olfr1199
0.10
0.18
0.05
0.07
0.08
0.12
0.02
0.01
0.02
0.01

Olfr12
0.38
0.35
0.28
0.29
0.28
0.31
0.25
0.23
0.27
0.28

Olfr120
0.15
0.16
0.07
0.12
0.13
0.13
0.11
0.10
0.11
0.13

Olfr1200
0.36
0.48
0.25
0.21
0.22
0.25
0.24
0.22
0.25
0.21

Olfr1201
0.18
0.24
0.14
0.15
0.14
0.18
0.18
0.16
0.13
0.12

Olfr1202
0.15
0.18
0.08
0.11
0.11
0.09
0.07
0.07
0.09
0.06

Olfr1204
0.07
0.08
0.07
0.12
0.07
0.10
0.07
0.05
0.08
0.08

Olfr1205
0.18
0.24
0.14
0.15
0.14
0.18
0.18
0.16
0.13
0.12

Olfr1206
0.18
0.24
0.14
0.15
0.14
0.18
0.18
0.16
0.13
0.12

Olfr1208
0.08
0.14
0.11
0.08
0.13
0.14
0.09
0.09
0.06
0.08

Olfr1209
0.21
0.26
0.15
0.17
0.15
0.19
0.15
0.16
0.16
0.14

Olfr121
0.23
0.29
0.19
0.20
0.20
0.21
0.12
0.14
0.13
0.09

Olfr1211
0.16
0.18
0.11
0.10
0.12
0.10
0.08
0.08
0.09
0.08

Olfr1212
0.04
0.06
0.03
0.01
0.04
0.05
0.02
0.02
0.03
0.03

Olfr1213
0.13
0.18
0.10
0.13
0.16
0.18
0.09
0.07
0.08
0.08

Olfr1214
0.04
0.10
0.05
0.06
0.12
0.12
0.02
0.04
0.07
0.06

Olfr1215
0.09
0.11
0.10
0.13
0.12
0.16
0.09
0.07
0.06
0.06

Olfr1216
0.06
0.07
0.07
0.08
0.06
0.03
0.04
0.04
0.05
0.04

Olfr1217
0.29
0.28
0.07
0.05
0.09
0.07
0.01
0.02
0.02
0.02

Olfr1218
0.07
0.09
0.08
0.08
0.10
0.13
0.06
0.05
0.06
0.06

Olfr1219
0.17
0.18
0.10
0.13
0.12
0.11
0.09
0.08
0.09
0.08

Olfr122
0.30
0.34
0.26
0.32
0.32
0.32
0.20
0.18
0.24
0.20

Olfr1220
0.13
0.16
0.07
0.07
0.11
0.12
0.08
0.06
0.06
0.07

Olfr1221
0.03
0.06
0.04
0.08
0.09
0.06
NA
0.00
0.02
NA

Olfr1222
0.31
0.34
0.23
0.26
0.28
0.32
0.26
0.24
0.20
0.21

Olfr1223
0.14
0.14
0.11
0.12
0.14
0.12
0.09
0.08
0.08
0.05

Olfr1225
0.18
0.20
0.15
0.16
0.16
0.18
0.13
0.12
0.13
0.12

Olfr1226
0.29
0.32
0.18
0.18
0.22
0.20
0.18
0.14
0.16
0.14

Olfr1228
0.09
0.11
0.05
0.08
0.07
0.06
0.04
0.04
0.04
0.04

Olfr1229
0.43
0.44
0.38
0.40
0.38
0.39
0.31
0.28
0.36
0.30

Olfr123
0.31
0.30
0.22
0.27
0.25
0.28
0.20
0.19
0.24
0.21

Olfr1230
0.19
0.22
0.21
0.23
0.19
0.21
0.18
0.16
0.18
0.16

Olfr1231
0.21
0.22
0.15
0.15
0.12
0.15
0.14
0.15
0.16
0.14

Olfr1232
0.06
0.05
0.08
0.08
0.09
0.07
0.03
0.03
0.04
0.03

Olfr1233
0.26
0.27
0.16
0.16
0.16
0.15
0.17
0.15
0.19
0.15

Olfr1234
0.15
0.15
0.11
0.13
0.16
0.17
0.11
0.09
0.12
0.10

Olfr1238
0.27
0.32
0.21
0.18
0.19
0.24
0.15
0.14
0.20
0.15

Olfr1239
0.26
0.29
0.18
0.22
0.18
0.23
0.20
0.16
0.17
0.19

Olfr124
0.17
0.17
0.18
0.21
0.19
0.21
0.13
0.12
0.21
0.15

Olfr1240
0.13
0.13
0.08
0.13
0.13
0.15
0.10
0.10
0.10
0.08

Olfr1241
0.14
0.20
0.10
0.10
0.13
0.16
0.09
0.08
0.12
0.10

Olfr1242
0.21
0.26
0.14
0.18
0.17
0.19
0.17
0.15
0.15
0.13

Olfr1243
0.13
0.14
0.07
0.09
0.08
0.08
0.07
0.07
0.07
0.07

Olfr1245
0.04
0.08
0.04
0.07
0.08
0.07
0.07
0.04
0.06
0.04

Olfr1246
0.06
0.03
0.02
0.09
0.06
0.04
0.01
0.00
NA
NA

Olfr1247
0.06
0.10
0.08
0.08
0.12
0.10
0.05
0.04
0.08
0.07

Olfr1248
0.02
0.03
0.02
0.06
0.10
0.10
0.02
0.00
NA
NA

Olfr1249
0.18
0.26
0.20
0.22
0.20
0.22
0.14
0.13
0.13
0.08

Olfr125
0.03
0.03
0.06
0.06
0.10
0.12
0.05
0.03
0.05
0.04

Olfr1250
0.02
0.03
0.04
0.04
0.05
0.07
0.07
0.05
0.02
0.03

Olfr1251
NA
NA
NA
0.01
0.02
NA
0.00
0.01
NA
NA

Olfr1252
0.34
0.30
0.10
0.19
0.13
0.13
0.14
0.10
0.11
0.12

Olfr1253
0.00
0.00
0.03
0.07
0.06
0.07
0.03
0.02
0.04
0.01

Olfr1254
0.01
0.00
0.01
0.03
0.06
0.08
NA
NA
NA
NA

Olfr1255
0.23
0.22
0.15
0.17
0.16
0.19
0.12
0.11
0.12
0.12

Olfr1256
0.20
0.17
0.17
0.19
0.18
0.20
0.18
0.15
0.12
0.14

Olfr1257
0.10
0.09
0.06
0.10
0.08
0.06
0.04
0.04
0.06
0.05

Olfr1258
0.22
0.29
0.17
0.20
0.16
0.17
0.15
0.15
0.16
0.16

Olfr1259
0.27
0.29
0.18
0.18
0.20
0.20
0.13
0.12
0.16
0.12

Olfr126
0.15
0.22
0.15
0.17
0.15
0.15
0.10
0.10
0.11
0.09

Olfr1260
0.39
0.42
0.25
0.27
0.26
0.28
0.21
0.20
0.23
0.21

Olfr1261
0.12
0.10
0.07
0.08
0.05
0.04
0.03
0.02
0.04
0.04

Olfr1262
0.34
0.29
0.20
0.16
0.23
0.20
0.16
0.16
0.20
0.20

Olfr1263
0.20
0.23
0.14
0.17
0.16
0.20
0.14
0.14
0.17
0.12

Olfr1264
0.23
0.30
0.17
0.21
0.17
0.19
0.16
0.14
0.16
0.14

Olfr1265
0.13
0.13
0.12
0.14
0.15
0.17
0.10
0.10
0.10
0.10

Olfr1269
0.13
0.13
0.12
0.14
0.15
0.17
0.10
0.10
0.10
0.10

Olfr127
0.15
0.22
0.15
0.17
0.15
0.15
0.10
0.10
0.11
0.09

Olfr1270
0.14
0.18
0.09
0.10
0.12
0.12
0.09
0.10
0.11
0.10

Olfr1271
0.13
0.14
0.14
0.17
0.20
0.23
0.13
0.10
0.15
0.07

Olfr1272
0.42
0.41
0.24
0.24
0.27
0.30
0.24
0.22
0.28
0.26

Olfr1273-ps
0.10
0.15
0.03
0.06
0.05
0.11
0.03
0.04
0.03
0.01

Olfr1274-ps
0.31
0.22
0.20
0.23
0.20
0.19
0.20
0.18
0.18
0.17

Olfr1275
0.11
0.16
0.12
0.12
0.12
0.15
0.09
0.08
0.07
0.09

Olfr1276
0.27
0.24
0.23
0.23
0.22
0.22
0.19
0.16
0.20
0.18

Olfr1277
0.31
0.32
0.23
0.24
0.26
0.31
0.24
0.21
0.23
0.22

Olfr1278
0.12
0.19
0.15
0.14
0.16
0.16
0.12
0.11
0.11
0.10

Olfr1279
0.38
0.37
0.28
0.29
0.29
0.32
0.23
0.22
0.23
0.22

Olfr128
0.15
0.22
0.15
0.17
0.15
0.15
0.10
0.10
0.11
0.09

Olfr1280
0.08
0.10
0.09
0.11
0.11
0.13
0.15
0.14
0.06
0.07

Olfr1281
0.14
0.16
0.08
0.10
0.09
0.11
0.03
0.03
0.04
0.02

Olfr1282
0.08
0.10
0.09
0.11
0.11
0.13
0.15
0.14
0.06
0.07

Olfr1283
0.08
0.10
0.09
0.11
0.11
0.13
0.15
0.14
0.06
0.07

Olfr1284
0.38
0.42
0.30
0.34
0.32
0.34
0.23
0.23
0.26
0.25

Olfr1286
0.08
0.10
0.09
0.11
0.11
0.13
0.15
0.14
0.06
0.07

Olfr1287
0.08
0.10
0.09
0.11
0.11
0.13
0.15
0.14
0.06
0.07

Olfr1288
0.08
0.11
0.06
0.08
0.08
0.08
0.06
0.05
0.05
0.05

Olfr1289
0.13
0.17
0.08
0.10
0.12
0.13
0.05
0.05
0.05
0.05

Olfr129
0.37
0.36
0.28
0.30
0.27
0.29
0.25
0.23
0.27
0.23

Olfr1290
0.09
0.10
0.14
0.13
0.19
0.15
0.05
0.05
0.08
0.09

Olfr1294
0.13
0.17
0.11
0.14
0.14
0.14
0.12
0.10
0.11
0.11

Olfr1295
0.17
0.16
0.09
0.16
0.14
0.16
0.13
0.10
0.07
0.09

Olfr1297
0.08
0.04
0.09
0.17
0.10
0.12
0.08
0.06
0.06
0.06

Olfr1298
0.16
0.33
0.07
0.10
0.11
0.12
0.06
0.04
0.04
0.05

Olfr1299
0.18
0.21
0.09
0.11
0.12
0.14
0.09
0.08
0.10
0.07

Olfr13
0.39
0.40
0.29
0.33
0.31
0.34
0.27
0.25
0.30
0.27

Olfr130
0.13
0.16
0.10
0.15
0.14
0.13
0.09
0.09
0.10
0.08

Olfr1300-ps1
0.07
0.10
0.06
0.07
0.06
0.11
0.06
0.03
0.04
0.04

Olfr1301
0.18
0.16
0.16
0.15
0.16
0.15
0.13
0.15
0.18
0.15

Olfr1302
0.08
0.12
0.07
0.03
0.07
0.07
0.03
0.04
0.02
0.02

Olfr1303
0.18
0.22
0.08
0.11
0.08
0.10
0.07
0.07
0.10
0.08

Olfr1305
0.15
0.12
0.13
0.12
0.14
0.16
0.12
0.11
0.13
0.11

Olfr1306
NA
0.02
0.01
0.02
0.04
0.03
NA
0.01
NA
NA

Olfr1307
0.26
0.26
0.13
0.15
0.18
0.16
0.13
0.13
0.16
0.12

Olfr1308
0.05
0.10
0.00
0.04
0.05
0.03
0.03
0.01
0.03
0.01

Olfr1309
0.19
0.22
0.18
0.23
0.18
0.18
0.16
0.14
0.17
0.14

Olfr131
0.18
0.25
0.14
0.16
0.17
0.18
0.14
0.13
0.14
0.13

Olfr1310
0.16
0.19
0.13
0.15
0.16
0.18
0.11
0.10
0.12
0.11

Olfr1311
0.23
0.21
0.15
0.15
0.17
0.18
0.15
0.13
0.16
0.14

Olfr1312
0.23
0.25
0.08
0.07
0.06
0.08
0.04
0.03
0.03
0.02

Olfr1313
0.17
0.23
0.11
0.12
0.16
0.17
0.14
0.09
0.12
0.11

Olfr1314
0.18
0.15
0.10
0.13
0.13
0.14
0.11
0.08
0.11
0.10

Olfr1316
0.13
0.15
0.11
0.14
0.15
0.15
0.10
0.08
0.11
0.09

Olfr1317
0.06
0.13
0.09
0.06
0.10
0.09
0.06
0.05
0.08
0.05

Olfr1318
0.12
0.19
0.11
0.10
0.10
0.14
0.08
0.08
0.13
0.08

Olfr132
0.23
0.18
0.18
0.16
0.19
0.21
0.13
0.13
0.15
0.15

Olfr1320
0.22
0.23
0.19
0.18
0.19
0.21
0.20
0.19
0.18
0.17

Olfr1321
0.23
0.30
0.16
0.23
0.19
0.22
0.13
0.13
0.16
0.14

Olfr1322
0.23
0.25
0.22
0.23
0.23
0.20
0.20
0.21
0.24
0.22

Olfr1323
0.15
0.17
0.12
0.11
0.15
0.16
0.11
0.11
0.16
0.11

Olfr1324
0.29
0.27
0.22
0.25
0.23
0.24
0.19
0.19
0.20
0.17

Olfr1325
0.11
0.14
0.08
0.13
0.12
0.09
0.07
0.07
0.08
0.09

Olfr1328
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1329
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr133
0.05
0.05
0.04
0.08
0.05
0.06
0.02
0.02
0.03
0.02

Olfr1330
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1331
0.34
0.37
0.18
0.24
0.24
0.29
0.20
0.18
0.18
0.18

Olfr1333
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1335
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1336
0.23
0.27
0.27
0.27
0.23
0.22
0.21
0.20
0.26
0.24

Olfr1337
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1338
0.24
0.23
0.23
0.23
0.23
0.28
0.26
0.25
0.23
0.19

Olfr1339
0.39
0.40
0.35
0.34
0.32
0.35
0.29
0.29
0.34
0.30

Olfr134
0.06
0.04
0.05
0.08
0.06
0.03
NA
0.01
0.01
0.01

Olfr1340
0.38
0.35
0.31
0.33
0.31
0.33
0.24
0.23
0.33
0.30

Olfr1341
0.20
0.23
0.16
0.19
0.18
0.21
0.13
0.11
0.15
0.16

Olfr1342
0.29
0.30
0.25
0.27
0.29
0.32
0.24
0.21
0.26
0.23

Olfr1344
0.30
0.31
0.27
0.29
0.31
0.33
0.28
0.25
0.32
0.29

Olfr1346
0.45
0.48
0.37
0.41
0.40
0.42
0.31
0.29
0.41
0.36

Olfr1347
0.56
0.59
0.40
0.41
0.43
0.44
0.40
0.40
0.45
0.42

Olfr1348
0.28
0.22
0.24
0.25
0.25
0.26
0.23
0.22
0.30
0.30

Olfr1349
0.43
0.43
0.39
0.40
0.36
0.38
0.37
0.34
0.42
0.40

Olfr135
0.04
0.05
0.06
0.06
0.08
0.08
0.05
0.04
0.03
0.04

Olfr1350
0.28
0.29
0.26
0.26
0.30
0.32
0.25
0.19
0.25
0.23

Olfr1351
0.18
0.20
0.15
0.17
0.19
0.24
0.13
0.13
0.15
0.14

Olfr1352
0.15
0.18
0.11
0.10
0.13
0.11
0.10
0.10
0.09
0.10

Olfr1353
0.23
0.25
0.13
0.14
0.16
0.16
0.09
0.08
0.11
0.11

Olfr1354
0.26
0.30
0.17
0.20
0.22
0.23
0.19
0.17
0.21
0.17

Olfr1355
0.26
0.30
0.17
0.20
0.22
0.23
0.19
0.17
0.21
0.17

Olfr1356
0.16
0.21
0.12
0.11
0.14
0.18
0.11
0.08
0.11
0.07

Olfr1357
0.27
0.30
0.22
0.24
0.23
0.26
0.20
0.19
0.21
0.20

Olfr1359
0.40
0.40
0.27
0.28
0.29
0.29
0.26
0.24
0.28
0.26

Olfr136
0.10
0.13
0.03
0.04
0.06
0.06
0.03
0.03
0.06
0.02

Olfr1360
0.40
0.40
0.27
0.28
0.29
0.29
0.26
0.24
0.28
0.26

Olfr1361
0.37
0.35
0.27
0.24
0.24
0.26
0.22
0.20
0.26
0.29

Olfr1362
0.41
0.43
0.32
0.35
0.34
0.40
0.29
0.28
0.32
0.31

Olfr1364
0.37
0.39
0.33
0.36
0.30
0.32
0.30
0.28
0.30
0.29

Olfr1366
0.37
0.42
0.31
0.34
0.29
0.31
0.27
0.24
0.29
0.26

Olfr1367
0.13
0.17
0.12
0.16
0.13
0.15
0.11
0.09
0.15
0.13

Olfr1368
0.16
0.14
0.08
0.10
0.10
0.10
0.07
0.07
0.12
0.07

Olfr137
0.28
0.34
0.26
0.24
0.28
0.31
0.23
0.22
0.24
0.20

Olfr1370
0.23
0.31
0.20
0.19
0.18
0.19
0.18
0.16
0.16
0.19

Olfr1371
0.34
0.29
0.15
0.22
0.41
0.27
0.24
0.22
0.23
0.23

Olfr1372-ps1
0.11
0.08
0.09
0.11
0.15
0.13
0.12
0.13
0.16
0.11

Olfr1373
0.34
0.29
0.15
0.22
0.41
0.27
0.24
0.22
0.23
0.23

Olfr1377
0.20
0.22
0.22
0.22
0.27
0.25
0.17
0.17
0.23
0.18

Olfr1378
0.30
0.32
0.27
0.31
0.28
0.34
0.32
0.30
0.30
0.24

Olfr138
0.04
0.04
0.02
0.04
0.03
0.03
NA
NA
NA
0.01

Olfr1380
0.34
0.29
0.15
0.22
0.41
0.27
0.24
0.22
0.23
0.23

Olfr1381
0.34
0.29
0.15
0.22
0.41
0.27
0.24
0.22
0.23
0.23

Olfr1382
0.34
0.29
0.15
0.22
0.41
0.27
0.24
0.22
0.23
0.23

Olfr1383
0.32
0.41
0.22
0.23
0.29
0.29
0.25
0.23
0.25
0.23

Olfr1384
0.34
0.34
0.20
0.20
0.24
0.25
0.19
0.18
0.20
0.18

Olfr1385
0.26
0.25
0.24
0.25
0.22
0.23
0.20
0.20
0.21
0.20

Olfr1386
0.26
0.25
0.24
0.25
0.22
0.23
0.20
0.20
0.21
0.20

Olfr1387
0.22
0.22
0.15
0.17
0.20
0.22
0.15
0.15
0.18
0.16

Olfr1388
0.44
0.44
0.29
0.34
0.33
0.36
0.27
0.26
0.31
0.28

Olfr1389
0.34
0.31
0.26
0.28
0.28
0.32
0.22
0.23
0.25
0.25

Olfr139
0.36
0.35
0.31
0.33
0.33
0.36
0.29
0.28
0.34
0.31

Olfr1390
0.28
0.28
0.28
0.30
0.30
0.29
0.24
0.26
0.26
0.26

Olfr1391
0.17
0.15
0.17
0.20
0.22
0.23
0.15
0.16
0.19
0.18

Olfr1392
0.37
0.36
0.29
0.28
0.31
0.34
0.23
0.23
0.32
0.25

Olfr1393
0.59
0.61
0.38
0.45
0.40
0.40
0.33
0.33
0.35
0.32

Olfr1394
0.51
0.52
0.45
0.46
0.46
0.50
0.37
0.35
0.46
0.42

Olfr1395
0.54
0.55
0.43
0.49
0.42
0.45
0.41
0.39
0.46
0.45

Olfr1396
0.30
0.34
0.25
0.54
0.23
0.24
0.23
0.21
0.25
0.24

Olfr140
0.36
0.36
0.28
0.29
0.28
0.33
0.24
0.25
0.28
0.26

Olfr1402
0.40
0.40
0.29
0.30
0.31
0.32
0.26
0.25
0.34
0.29

Olfr1404
0.18
0.17
0.13
0.11
0.16
0.15
0.11
0.09
0.12
0.10

Olfr1406
0.14
0.16
0.17
0.21
0.19
0.19
0.13
0.12
0.13
0.12

Olfr1408
0.20
0.22
0.20
0.20
0.23
0.25
0.15
0.16
0.17
0.14

Olfr141
0.15
0.15
0.15
0.15
0.13
0.16
0.13
0.11
0.12
0.09

Olfr1410
0.54
0.56
0.41
0.47
0.40
0.42
0.37
0.35
0.42
0.40

Olfr1411
0.35
0.31
0.27
0.27
0.23
0.22
0.24
0.23
0.27
0.24

Olfr1412
0.40
0.41
0.32
0.35
0.33
0.32
0.26
0.25
0.31
0.31

Olfr1413
0.35
0.39
0.35
0.36
0.36
0.37
0.32
0.31
0.36
0.34

Olfr1414
0.37
0.38
0.33
0.35
0.33
0.35
0.37
0.33
0.37
0.34

Olfr1415
0.37
0.38
0.33
0.35
0.33
0.35
0.37
0.33
0.37
0.34

Olfr1416
0.37
0.38
0.33
0.35
0.33
0.35
0.37
0.33
0.37
0.34

Olfr1417
0.36
0.37
0.30
0.34
0.30
0.33
0.25
0.24
0.28
0.26

Olfr1418
0.42
0.47
0.23
0.29
0.27
0.30
0.18
0.19
0.19
0.19

Olfr1419
0.24
0.27
0.22
0.24
0.21
0.23
0.21
0.20
0.26
0.24

Olfr142
0.20
0.19
0.09
0.12
0.12
0.14
0.10
0.09
0.11
0.09

Olfr1420
0.26
0.25
0.28
0.27
0.25
0.25
0.20
0.19
0.22
0.21

Olfr1423
0.24
0.26
0.24
0.21
0.19
0.20
0.18
0.18
0.26
0.20

Olfr1424
0.08
0.09
0.11
0.11
0.13
0.15
0.06
0.05
0.07
0.05

Olfr1425
0.25
0.28
0.23
0.28
0.26
0.28
0.23
0.21
0.26
0.22

Olfr1426
0.44
0.43
0.25
0.29
0.27
0.28
0.21
0.19
0.22
0.21

Olfr1427
0.23
0.26
0.22
0.19
0.25
0.25
0.16
0.17
0.17
0.16

Olfr1428
0.34
0.41
0.26
0.29
0.27
0.27
0.24
0.23
0.27
0.29

Olfr143
0.24
0.26
0.23
0.24
0.23
0.26
0.21
0.17
0.21
0.18

Olfr1431
0.20
0.25
0.14
0.15
0.12
0.22
0.11
0.07
0.09
0.07

Olfr1434
0.05
0.08
0.04
0.04
0.07
0.06
0.00
0.00
0.00
0.01

Olfr1436
0.14
0.18
0.07
0.06
0.16
0.16
0.03
0.04
0.02
NA

Olfr1437
0.23
0.20
0.17
0.18
0.13
0.13
0.15
0.13
0.12
0.11

Olfr1440
0.22
0.25
0.19
0.21
0.21
0.22
0.18
0.17
0.22
0.21

Olfr1441
0.20
0.24
0.16
0.17
0.18
0.21
0.16
0.13
0.18
0.17

Olfr1442
0.17
0.21
0.12
0.14
0.18
0.20
0.10
0.10
0.13
0.10

Olfr1443
0.08
0.08
0.05
0.07
0.07
0.08
0.03
0.02
0.06
0.03

Olfr1444
0.28
0.30
0.20
0.20
0.13
0.16
0.13
0.12
0.13
0.14

Olfr1445
0.20
0.19
0.18
0.20
0.17
0.18
0.15
0.13
0.14
0.14

Olfr1446
0.11
0.10
0.10
0.11
0.13
0.12
0.08
0.06
0.08
0.07

Olfr1447
0.11
0.14
0.13
0.18
0.14
0.18
0.07
0.06
0.06
0.06

Olfr1448
0.06
0.06
0.06
0.07
0.07
0.09
0.05
0.04
0.05
0.04

Olfr1449
0.28
0.29
0.21
0.22
0.23
0.28
0.21
0.19
0.19
0.16

Olfr145
0.34
0.36
0.19
0.21
0.19
0.23
0.19
0.18
0.20
0.18

Olfr1450
0.22
0.30
0.20
0.20
0.20
0.24
0.15
0.15
0.16
0.16

Olfr1451
0.10
0.17
0.10
0.12
0.10
0.11
0.07
0.07
0.11
0.05

Olfr1453
0.14
0.18
0.13
0.17
0.17
0.19
0.10
0.10
0.09
0.11

Olfr1454
0.12
0.15
0.08
0.08
0.07
0.10
0.06
0.04
0.05
0.02

Olfr1457
0.05
0.10
0.07
0.10
0.07
0.10
0.02
0.01
0.02
0.02

Olfr1459
0.11
0.09
0.13
0.10
0.09
0.10
0.07
0.06
0.08
0.07

Olfr146
0.11
0.15
0.15
0.15
0.12
0.13
0.10
0.09
0.10
0.08

Olfr1461
0.32
0.42
0.16
0.17
0.21
0.20
0.13
0.13
0.17
0.11

Olfr1462
0.07
0.06
0.05
0.07
0.08
0.07
0.03
0.03
0.04
0.04

Olfr1463
0.26
0.22
0.19
0.20
0.18
0.19
0.23
0.20
0.25
0.23

Olfr1465
0.32
0.34
0.25
0.28
0.28
0.31
0.19
0.19
0.22
0.20

Olfr1466
0.18
0.18
0.14
0.14
0.11
0.12
0.08
0.08
0.10
0.10

Olfr1467
0.20
0.20
0.12
0.10
0.11
0.12
0.10
0.09
0.08
0.08

Olfr1469
0.18
0.21
0.10
0.12
0.09
0.12
0.08
0.09
0.09
0.08

Olfr147
0.44
0.49
0.35
0.36
0.34
0.34
0.29
0.28
0.32
0.29

Olfr1471
0.09
0.16
0.04
0.06
0.05
0.07
0.09
0.05
0.03
0.02

Olfr1472
0.10
0.19
0.08
0.11
0.10
0.12
0.08
0.05
0.10
0.07

Olfr1474
0.14
0.19
0.08
0.12
0.13
0.13
0.12
0.10
0.10
0.09

Olfr1475
0.13
0.15
0.09
0.14
0.10
0.20
0.03
0.03
0.04
0.03

Olfr1477
0.11
0.17
NA
0.01
0.06
0.06
NA
NA
NA
NA

Olfr148
0.28
0.33
0.20
0.23
0.23
0.23
0.18
0.17
0.20
0.20

Olfr1480
0.18
0.19
0.13
0.14
0.16
0.18
0.10
0.09
0.11
0.07

Olfr1484
0.20
0.19
0.11
0.09
0.14
0.16
0.11
0.10
0.06
0.07

Olfr1487
0.02
0.04
0.10
0.10
0.16
0.21
0.02
0.02
0.04
0.05

Olfr1489
0.12
0.15
0.11
0.11
0.10
0.09
0.09
0.08
0.08
0.07

Olfr149
0.48
0.53
0.43
0.44
0.39
0.39
0.34
0.33
0.38
0.34

Olfr1490
0.29
0.28
0.20
0.25
0.23
0.24
0.19
0.19
0.23
0.21

Olfr1491
0.30
0.33
0.27
0.27
0.28
0.32
0.24
0.22
0.29
0.26

Olfr1494
0.10
0.14
0.08
0.10
0.14
0.19
0.07
0.06
0.10
0.05

Olfr1495
0.29
0.34
0.23
0.26
0.23
0.26
0.20
0.21
0.24
0.26

Olfr1496
0.06
0.07
0.07
0.05
0.05
0.06
0.05
0.04
0.04
0.03

Olfr1497
0.40
0.43
0.33
0.39
0.40
0.44
0.32
0.30
0.38
0.33

Olfr1499
0.18
0.25
0.11
0.14
0.16
0.16
0.12
0.09
0.11
0.11

Olfr15
0.20
0.17
0.18
0.17
0.14
0.16
0.15
0.14
0.15
0.18

Olfr150
0.25
0.27
0.20
0.25
0.20
0.25
0.18
0.19
0.20
0.18

Olfr1500
0.29
0.30
0.23
0.26
0.27
0.26
0.21
0.20
0.24
0.22

Olfr1501
0.11
0.14
0.06
0.11
0.11
0.18
0.05
0.04
0.08
0.05

Olfr1502
0.39
0.48
0.29
0.31
0.32
0.35
0.23
0.22
0.27
0.24

Olfr1504
0.25
0.28
0.12
0.17
0.15
0.17
0.11
0.10
0.11
0.11

Olfr1505
0.27
0.27
0.19
0.23
0.23
0.25
0.14
0.11
0.24
0.17

Olfr1506
0.30
0.31
0.21
0.24
0.25
0.28
0.25
0.24
0.22
0.20

Olfr1507
0.22
0.23
0.09
0.10
0.15
0.13
0.10
0.07
0.10
0.09

Olfr1508
0.27
0.34
0.21
0.24
0.21
0.21
0.21
0.19
0.22
0.18

Olfr1509
0.18
0.22
0.12
0.14
0.14
0.13
0.12
0.11
0.12
0.13

Olfr151
0.11
0.09
0.11
0.13
0.13
0.11
0.13
0.10
0.12
0.10

Olfr1510
0.51
0.52
0.38
0.36
0.35
0.35
0.34
0.32
0.40
0.34

Olfr1511
0.39
0.37
0.23
0.22
0.23
0.25
0.20
0.19
0.27
0.22

Olfr1512
0.19
0.19
0.19
0.17
0.18
0.24
0.15
0.14
0.15
0.16

Olfr1513
0.19
0.19
0.19
0.17
0.18
0.24
0.15
0.14
0.15
0.16

Olfr152
0.20
0.30
0.18
0.23
0.26
0.25
0.13
0.12
0.17
0.15

Olfr153
0.16
0.24
0.10
0.15
0.15
0.16
0.11
0.11
0.11
0.11

Olfr1532-ps1
0.48
0.49
0.37
0.40
0.36
0.37
0.34
0.32
0.37
0.36

Olfr1535
0.33
0.36
0.26
0.29
0.28
0.32
0.23
0.20
0.24
0.25

Olfr1537
0.19
0.17
0.13
0.16
0.12
0.11
0.14
0.15
0.08
0.06

Olfr154
0.10
0.18
0.08
0.10
0.13
0.11
0.14
0.11
0.10
0.10

Olfr155
0.35
0.33
0.25
0.30
0.31
0.33
0.23
0.22
0.29
0.26

Olfr156
0.18
0.18
0.14
0.15
0.16
0.16
0.12
0.11
0.16
0.14

Olfr157
0.41
0.44
0.37
0.39
0.42
0.45
0.30
0.30
0.33
0.31

Olfr159
0.26
0.25
0.24
0.23
0.20
0.23
0.21
0.19
0.21
0.21

Olfr16
0.30
0.30
0.27
0.27
0.25
0.28
0.22
0.20
0.27
0.22

Olfr160
0.23
0.25
0.23
0.25
0.25
0.28
0.19
0.19
0.21
0.20

Olfr161
0.36
0.41
0.31
0.32
0.28
0.30
0.21
0.20
0.26
0.24

Olfr164
0.20
0.20
0.14
0.14
0.16
0.17
0.13
0.12
0.20
0.13

Olfr165
0.24
0.29
0.20
0.20
0.21
0.23
0.18
0.15
0.19
0.15

Olfr166
0.25
0.32
0.24
0.22
0.30
0.41
0.24
0.22
0.22
0.17

Olfr167
0.30
0.29
0.11
0.16
0.17
0.16
0.12
0.11
0.13
0.10

Olfr168
0.21
0.26
0.14
0.14
0.19
0.20
0.12
0.11
0.15
0.12

Olfr169
0.43
0.47
0.28
0.32
0.31
0.36
0.30
0.28
0.31
0.27

Olfr17
0.23
0.22
0.19
0.24
0.23
0.27
0.19
0.18
0.22
0.19

Olfr170
0.43
0.47
0.28
0.32
0.31
0.36
0.30
0.28
0.31
0.27

Olfr171
0.43
0.47
0.28
0.32
0.31
0.36
0.30
0.28
0.31
0.27

Olfr172
0.22
0.29
0.10
0.15
0.23
0.15
0.18
0.11
0.17
0.14

Olfr173
0.07
0.13
0.08
0.11
0.13
0.08
0.07
0.05
0.10
0.05

Olfr175-ps1
0.03
0.07
0.05
0.07
0.06
0.08
0.00
NA
0.01
NA

Olfr176
0.01
0.05
0.04
0.04
0.10
0.08
0.03
0.01
0.04
0.02

Olfr177
0.01
0.05
0.04
0.04
0.10
0.08
0.03
0.01
0.04
0.02

Olfr178
0.06
0.08
0.03
0.11
0.08
0.12
0.00
NA
0.00
NA

Olfr18
0.12
0.11
0.09
0.08
0.12
0.12
0.09
0.07
0.11
0.08

Olfr180
0.22
0.20
0.22
0.23
0.24
0.24
0.20
0.18
0.20
0.19

Olfr181
0.02
0.03
0.05
0.05
0.06
0.10
0.01
0.00
0.01
0.01

Olfr183
0.04
0.08
0.05
0.06
0.08
0.09
0.02
0.02
0.07
0.04

Olfr186
0.11
0.16
0.07
0.08
0.08
0.09
0.07
0.05
0.08
0.06

Olfr187
0.09
0.10
0.08
0.07
0.10
0.09
0.04
0.02
0.05
0.06

Olfr19
0.26
0.27
0.25
0.25
0.24
0.26
0.21
0.18
0.20
0.19

Olfr190
NA
0.01
NA
0.02
0.07
0.04
NA
NA
0.01
0.00

Olfr191
0.11
0.14
0.06
0.10
0.09
0.08
0.05
0.05
0.02
0.02

Olfr192
NA
0.06
NA
0.01
0.04
0.06
NA
0.01
NA
NA

Olfr193
0.00
NA
0.02
0.04
0.07
0.08
0.00
NA
NA
NA

Olfr194
0.09
0.08
0.07
0.10
0.08
0.12
0.08
0.08
0.04
0.04

Olfr195
0.15
0.12
0.11
0.11
0.15
0.17
0.06
0.07
0.07
0.09

Olfr196
0.01
0.04
NA
0.03
0.02
0.02
NA
NA
NA
NA

Olfr197
0.22
0.22
0.18
0.24
0.18
0.21
0.20
0.16
0.16
0.16

Olfr198
0.30
0.27
0.13
0.15
0.27
0.28
0.13
0.12
0.12
0.11

Olfr199
0.07
0.10
0.06
0.09
0.10
0.10
0.05
0.05
0.04
0.02

Olfr2
0.11
0.13
0.09
0.11
0.11
0.12
0.09
0.09
0.09
0.07

Olfr20
0.22
0.23
0.19
0.23
0.20
0.21
0.19
0.18
0.20
0.15

Olfr201
0.10
0.15
0.10
0.15
0.10
0.13
0.06
0.06
0.05
0.07

Olfr202
0.18
0.17
0.14
0.15
0.14
0.16
0.15
0.13
0.16
0.15

Olfr203
NA
NA
0.07
0.05
0.03
0.04
0.01
NA
NA
NA

Olfr204
0.11
0.12
0.08
0.12
0.11
0.11
0.09
0.08
0.10
0.08

Olfr205
0.11
0.12
0.08
0.12
0.11
0.11
0.09
0.08
0.10
0.08

Olfr206
0.00
0.05
0.08
0.07
0.08
0.11
0.01
0.00
0.03
NA

Olfr207
0.11
0.09
0.14
0.12
0.14
0.17
0.11
0.10
0.11
0.11

Olfr208
0.11
0.09
0.14
0.12
0.14
0.17
0.11
0.10
0.11
0.11

Olfr209
0.11
0.09
0.14
0.12
0.14
0.17
0.11
0.10
0.11
0.11

Olfr211
0.30
0.31
0.27
0.28
0.24
0.26
0.21
0.19
0.26
0.22

Olfr212
0.30
0.36
0.19
0.19
0.17
0.18
0.15
0.14
0.19
0.21

Olfr213
0.28
0.33
0.24
0.28
0.20
0.24
0.22
0.21
0.24
0.25

Olfr214
0.37
0.37
0.30
0.32
0.30
0.29
0.29
0.25
0.30
0.27

Olfr215
0.33
0.34
0.27
0.28
0.27
0.30
0.24
0.24
0.29
0.28

Olfr218
0.16
0.15
0.14
0.14
0.13
0.17
0.11
0.09
0.12
0.11

Olfr220
0.34
0.36
0.26
0.30
0.29
0.29
0.24
0.22
0.25
0.26

Olfr221
0.34
0.36
0.28
0.33
0.33
0.33
0.26
0.24
0.29
0.27

Olfr222
0.40
0.42
0.34
0.37
0.36
0.39
0.34
0.31
0.36
0.34

Olfr223
0.29
0.31
0.20
0.22
0.20
0.21
0.18
0.16
0.20
0.16

Olfr224
0.05
0.07
0.03
0.05
0.10
0.05
0.06
0.05
0.04
0.05

Olfr225
0.32
0.33
0.30
0.30
0.30
0.30
0.29
0.25
0.28
0.32

Olfr228
0.02
0.03
0.03
0.03
0.08
0.07
0.03
0.03
0.05
0.03

Olfr229
0.01
0.04
0.02
0.06
0.05
0.04
0.01
0.01
0.02
0.02

Olfr23
0.23
0.20
0.19
0.20
0.19
0.23
0.16
0.15
0.16
0.18

Olfr231
0.38
0.36
0.29
0.32
0.30
0.34
0.26
0.24
0.28
0.27

Olfr235
0.23
0.20
0.17
0.18
0.13
0.13
0.15
0.13
0.12
0.11

Olfr237-ps1
0.12
0.17
0.10
0.11
0.12
0.17
0.12
0.10
0.13
0.10

Olfr239
0.79
0.86
0.52
0.55
0.55
0.58
0.51
0.49
0.62
0.57

Olfr24
0.22
0.25
0.19
0.20
0.23
0.28
0.18
0.17
0.20
0.18

Olfr242
0.08
0.09
0.08
0.11
0.10
0.13
0.07
0.06
0.05
0.06

Olfr243
NA
NA
0.03
0.04
0.04
0.10
NA
0.02
0.02
0.03

Olfr247
0.46
0.48
0.29
0.31
0.28
0.31
0.28
0.26
0.28
0.23

Olfr248
0.24
0.25
0.11
0.15
0.20
0.19
0.12
0.10
0.09
0.10

Olfr25
0.15
0.13
0.09
0.11
0.11
0.12
0.12
0.08
0.09
0.07

Olfr250
0.18
0.24
0.13
0.17
0.15
0.15
0.13
0.11
0.13
0.12

Olfr251
0.17
0.20
0.13
0.16
0.17
0.20
0.13
0.11
0.13
0.11

Olfr255
0.22
0.23
0.19
0.23
0.20
0.21
0.19
0.18
0.20
0.15

Olfr257
0.33
0.36
0.29
0.32
0.31
0.33
0.26
0.24
0.30
0.30

Olfr259
0.08
0.11
0.05
0.06
0.09
0.07
0.02
0.01
0.03
0.02

Olfr26
0.21
0.22
0.17
0.16
0.16
0.18
0.15
0.14
0.14
0.13

Olfr262
0.22
0.23
0.17
0.20
0.17
0.15
0.14
0.13
0.15
0.12

Olfr263
0.08
0.05
0.06
0.10
0.13
0.08
0.05
0.05
0.05
0.04

Olfr266
0.26
0.24
0.21
0.20
0.20
0.20
0.17
0.17
0.18
0.18

Olfr267
0.43
0.37
0.30
0.32
0.30
0.28
0.29
0.28
0.32
0.31

Olfr27
0.08
0.09
0.08
0.11
0.10
0.13
0.07
0.06
0.05
0.06

Olfr270
0.09
0.13
0.09
0.11
0.10
0.11
0.08
0.08
0.14
0.11

Olfr272
0.24
0.26
0.21
0.22
0.27
0.29
0.19
0.19
0.20
0.21

Olfr273
0.23
0.21
0.19
0.18
0.20
0.22
0.16
0.15
0.16
0.18

Olfr275
0.15
0.22
0.16
0.17
0.19
0.21
0.20
0.16
0.15
0.17

Olfr279
0.34
0.27
0.29
0.30
0.28
0.30
0.30
0.28
0.36
0.35

Olfr281
0.32
0.36
0.23
0.28
0.27
0.30
0.25
0.25
0.27
0.27

Olfr282
0.49
0.48
0.37
0.40
0.38
0.41
0.36
0.33
0.41
0.36

Olfr283
0.32
0.35
0.27
0.30
0.31
0.34
0.24
0.23
0.28
0.28

Olfr284
0.35
0.37
0.28
0.29
0.29
0.32
0.27
0.25
0.36
0.34

Olfr285
0.33
0.36
0.29
0.32
0.31
0.33
0.26
0.24
0.30
0.30

Olfr286
0.25
0.26
0.20
0.22
0.25
0.28
0.20
0.19
0.22
0.22

Olfr288
0.29
0.38
0.21
0.21
0.22
0.25
0.20
0.16
0.20
0.14

Olfr29-ps1
0.33
0.35
0.29
0.30
0.30
0.33
0.25
0.26
0.28
0.27

Olfr290
0.15
0.13
0.04
0.07
0.07
0.06
0.04
0.04
0.05
0.03

Olfr291
0.12
0.13
0.07
0.07
0.10
0.10
0.07
0.06
0.05
0.08

Olfr292
0.14
0.19
0.08
0.09
0.15
0.16
0.07
0.04
0.07
0.05

Olfr293
0.18
0.20
0.18
0.16
0.22
0.24
0.12
0.12
0.13
0.15

Olfr294
0.09
0.12
0.05
0.12
0.07
0.08
0.10
0.09
0.09
0.10

Olfr295
0.09
0.14
0.04
0.05
0.06
0.06
0.03
0.02
0.02
0.03

Olfr297
0.17
0.17
0.14
0.16
0.17
0.17
0.11
0.09
0.13
0.11

Olfr298
0.08
0.08
0.09
0.12
0.10
0.14
0.07
0.06
0.08
0.05

Olfr299
0.03
0.04
NA
NA
NA
NA
NA
NA
0.01
NA

Olfr3
0.28
0.31
0.25
0.23
0.22
0.24
0.20
0.20
0.23
0.22

Olfr30
0.41
0.39
0.33
0.32
0.35
0.36
0.31
0.30
0.38
0.36

Olfr301
0.10
0.13
0.06
0.12
0.09
0.11
0.04
0.04
0.07
0.06

Olfr303
0.15
0.20
0.13
0.13
0.17
0.22
0.12
0.12
0.17
0.14

Olfr304
0.12
0.18
0.09
0.12
0.08
0.08
0.07
0.05
0.11
0.05

Olfr305
0.21
0.22
0.18
0.21
0.16
0.22
0.15
0.14
0.17
0.13

Olfr307
0.23
0.24
0.22
0.21
0.22
0.24
0.15
0.15
0.21
0.18

Olfr308
0.12
0.13
0.11
0.11
0.14
0.15
0.09
0.07
0.07
0.09

Olfr309
0.22
0.26
0.19
0.23
0.20
0.26
0.21
0.19
0.22
0.19

Olfr31
0.33
0.37
0.26
0.28
0.25
0.28
0.23
0.23
0.26
0.24

Olfr310
0.09
0.13
0.05
0.08
0.05
0.04
0.07
0.06
0.08
0.05

Olfr311
0.19
0.18
0.16
0.19
0.16
0.18
0.14
0.13
0.16
0.19

Olfr312
0.23
0.24
0.19
0.23
0.25
0.24
0.17
0.17
0.21
0.21

Olfr313
0.28
0.33
0.22
0.22
0.25
0.24
0.18
0.17
0.19
0.19

Olfr314
0.58
0.57
0.49
0.48
0.44
0.49
0.38
0.38
0.50
0.46

Olfr315
0.40
0.40
0.33
0.33
0.32
0.34
0.30
0.30
0.38
0.37

Olfr316
0.50
0.52
0.45
0.41
0.42
0.43
0.36
0.31
0.36
0.39

Olfr317
0.34
0.36
0.28
0.29
0.32
0.31
0.29
0.26
0.31
0.30

Olfr318
0.19
0.21
0.18
0.17
0.22
0.27
0.18
0.16
0.21
0.18

Olfr319
0.25
0.23
0.20
0.24
0.26
0.26
0.18
0.14
0.20
0.22

Olfr32
0.18
0.15
0.12
0.09
0.12
0.15
0.11
0.08
0.10
0.09

Olfr320
0.55
0.55
0.30
0.38
0.30
0.32
0.32
0.30
0.32
0.30

Olfr322
0.38
0.39
0.36
0.35
0.36
0.39
0.34
0.31
0.41
0.38

Olfr323
0.15
0.17
0.13
0.17
0.18
0.18
0.13
0.12
0.18
0.15

Olfr324
0.26
0.26
0.19
0.24
0.24
0.23
0.21
0.20
0.25
0.22

Olfr325
0.16
0.20
0.13
0.16
0.16
0.16
0.09
0.08
0.11
0.10

Olfr328
0.42
0.42
0.31
0.34
0.30
0.32
0.28
0.24
0.31
0.28

Olfr329-ps
0.34
0.37
0.30
0.29
0.27
0.26
0.27
0.26
0.35
0.31

Olfr33
0.29
0.22
0.19
0.24
0.23
0.29
0.19
0.18
0.21
0.21

Olfr330
0.36
0.30
0.21
0.24
0.31
0.28
0.27
0.24
0.30
0.28

Olfr331
0.34
0.37
0.30
0.29
0.27
0.26
0.27
0.26
0.35
0.31

Olfr332
0.35
0.40
0.25
0.29
0.27
0.28
0.27
0.24
0.32
0.27

Olfr338
0.17
0.18
0.05
0.11
0.17
0.14
0.08
0.07
0.08
0.09

Olfr339
0.07
0.07
0.06
0.08
0.12
0.10
0.07
0.04
0.03
0.03

Olfr340
0.05
0.06
0.04
0.10
0.09
0.11
0.06
0.04
0.06
0.03

Olfr341
0.23
0.26
0.20
0.22
0.20
0.23
0.18
0.16
0.16
0.16

Olfr342
0.08
0.10
0.09
0.13
0.13
0.14
0.12
0.10
0.11
0.08

Olfr344
0.29
0.31
0.12
0.17
0.18
0.20
0.11
0.09
0.10
0.08

Olfr345
0.04
0.06
0.08
0.07
0.08
0.12
0.09
0.05
0.05
0.05

Olfr346
0.17
0.23
0.13
0.15
0.15
0.15
0.12
0.12
0.12
0.09

Olfr347
0.17
0.21
0.12
0.15
0.16
0.16
0.11
0.11
0.12
0.09

Olfr348
0.15
0.15
0.11
0.14
0.19
0.19
0.11
0.10
0.10
0.08

Olfr350
0.13
0.16
0.11
0.11
0.13
0.17
0.10
0.09
0.11
0.08

Olfr351
0.30
0.29
0.23
0.26
0.25
0.31
0.20
0.19
0.22
0.21

Olfr352
0.24
0.25
0.19
0.21
0.18
0.20
0.17
0.15
0.16
0.13

Olfr353
0.17
0.17
0.17
0.20
0.17
0.18
0.13
0.12
0.14
0.13

Olfr354
0.25
0.30
0.19
0.20
0.23
0.26
0.20
0.17
0.21
0.18

Olfr355
0.11
0.19
0.12
0.10
0.13
0.13
0.11
0.09
0.11
0.08

Olfr356
0.25
0.26
0.18
0.19
0.20
0.21
0.16
0.15
0.17
0.17

Olfr357
0.19
0.26
0.16
0.17
0.18
0.18
0.12
0.12
0.14
0.11

Olfr358
0.10
0.11
0.09
0.13
0.11
0.11
0.13
0.11
0.07
0.07

Olfr360
0.10
0.11
0.09
0.13
0.11
0.11
0.13
0.11
0.07
0.07

Olfr361
0.36
0.38
0.25
0.18
0.21
0.20
0.16
0.13
0.19
0.18

Olfr362
0.31
0.31
0.29
0.29
0.28
0.30
0.30
0.27
0.32
0.30

Olfr365
0.34
0.35
0.28
0.30
0.29
0.33
0.26
0.25
0.31
0.29

Olfr366
0.25
0.28
0.23
0.24
0.21
0.21
0.18
0.18
0.22
0.20

Olfr367-ps
0.30
0.36
0.25
0.20
0.24
0.21
0.21
0.20
0.25
0.24

Olfr368
0.39
0.40
0.39
0.38
0.37
0.42
0.31
0.30
0.38
0.36

Olfr370
0.43
0.40
0.31
0.34
0.35
0.36
0.29
0.27
0.31
0.30

Olfr371
0.31
0.35
0.26
0.31
0.27
0.29
0.26
0.23
0.28
0.26

Olfr372
0.44
0.43
0.32
0.36
0.38
0.41
0.32
0.31
0.36
0.34

Olfr373
0.48
0.42
0.27
0.34
0.32
0.32
0.27
0.25
0.30
0.30

Olfr374
0.28
0.29
0.23
0.22
0.23
0.25
0.19
0.19
0.24
0.23

Olfr376
0.24
0.28
0.19
0.22
0.21
0.22
0.16
0.13
0.18
0.17

Olfr378
0.11
0.13
0.05
0.08
0.09
0.08
0.06
0.05
0.07
0.06

Olfr38
0.28
0.32
0.26
0.27
0.28
0.28
0.21
0.19
0.26
0.22

Olfr380
0.08
0.07
0.04
0.05
0.06
0.08
0.05
0.04
0.05
0.04

Olfr381
0.13
0.15
0.16
0.17
0.16
0.16
0.13
0.12
0.15
0.14

Olfr382
0.20
0.22
0.13
0.18
0.17
0.15
0.12
0.11
0.15
0.14

Olfr384
0.14
0.14
0.07
0.11
0.11
0.12
0.07
0.06
0.08
0.08

Olfr385
0.09
0.15
0.05
0.07
0.09
0.09
0.07
0.06
0.06
0.04

Olfr389
0.22
0.24
0.13
0.17
0.16
0.16
0.13
0.12
0.12
0.11

Olfr39
0.34
0.37
0.26
0.26
0.27
0.29
0.22
0.20
0.24
0.21

Olfr390
0.11
0.13
0.10
0.11
0.12
0.15
0.11
0.09
0.10
0.09

Olfr391-ps
0.22
0.23
0.19
0.23
0.20
0.21
0.19
0.18
0.20
0.15

Olfr392
0.05
0.02
0.05
0.06
0.05
0.06
0.04
0.04
0.03
0.03

Olfr393
0.15
0.18
0.12
0.12
0.13
0.14
0.09
0.06
0.10
0.09

Olfr394
0.19
0.21
0.15
0.17
0.20
0.21
0.13
0.12
0.15
0.13

Olfr395
0.22
0.23
0.19
0.23
0.20
0.21
0.19
0.18
0.20
0.15

Olfr397
0.16
0.15
0.12
0.16
0.16
0.19
0.10
0.10
0.14
0.11

Olfr398
0.45
0.45
0.36
0.39
0.38
0.39
0.33
0.30
0.35
0.31

Olfr399
0.34
0.36
0.28
0.28
0.27
0.31
0.22
0.19
0.22
0.23

Olfr401
0.64
0.66
0.43
0.49
0.44
0.47
0.34
0.36
0.43
0.41

Olfr402
0.35
0.35
0.29
0.28
0.27
0.28
0.24
0.22
0.27
0.24

Olfr403
0.21
0.21
0.18
0.20
0.16
0.20
0.20
0.19
0.20
0.17

Olfr406
0.32
0.34
0.23
0.27
0.23
0.26
0.26
0.23
0.23
0.23

Olfr410
0.23
0.23
0.17
0.20
0.19
0.18
0.18
0.17
0.18
0.17

Olfr411
0.47
0.46
0.38
0.40
0.36
0.41
0.35
0.34
0.37
0.33

Olfr412
0.38
0.40
0.35
0.38
0.35
0.39
0.31
0.28
0.36
0.33

Olfr414
0.35
0.32
0.28
0.30
0.30
0.31
0.25
0.25
0.30
0.30

Olfr417
0.41
0.45
0.33
0.41
0.36
0.39
0.32
0.32
0.32
0.31

Olfr418
0.23
0.26
0.20
0.21
0.22
0.25
0.17
0.16
0.20
0.18

Olfr419
0.30
0.35
0.26
0.28
0.25
0.26
0.24
0.23
0.26
0.24

Olfr420
0.23
0.27
0.22
0.22
0.20
0.22
0.21
0.20
0.23
0.20

Olfr421-ps1
0.18
0.29
0.13
0.18
0.17
0.20
0.14
0.13
0.13
0.11

Olfr424
0.34
0.32
0.23
0.30
0.29
0.36
0.22
0.19
0.24
0.24

Olfr426
0.23
0.28
0.18
0.23
0.19
0.19
0.14
0.13
0.15
0.14

Olfr427
0.23
0.28
0.18
0.23
0.19
0.19
0.14
0.13
0.15
0.14

Olfr429
0.25
0.21
0.20
0.22
0.22
0.26
0.18
0.15
0.17
0.19

Olfr43
0.09
0.09
0.07
0.09
0.07
0.07
0.03
0.03
0.05
0.03

Olfr430
0.17
0.17
0.10
0.14
0.14
0.15
0.12
0.13
0.13
0.11

Olfr432
0.18
0.19
0.19
0.20
0.19
0.15
0.14
0.13
0.23
0.23

Olfr433
0.40
0.42
0.28
0.37
0.38
0.32
0.28
0.26
0.41
0.38

Olfr434
0.22
0.23
0.21
0.25
0.21
0.25
0.18
0.17
0.25
0.24

Olfr435
0.36
0.39
0.29
0.29
0.28
0.33
0.27
0.27
0.33
0.31

Olfr437
0.28
0.30
0.21
0.27
0.23
0.25
0.20
0.20
0.21
0.21

Olfr44
0.09
0.09
0.07
0.10
0.09
0.10
0.06
0.07
0.06
0.04

Olfr441
0.31
0.32
0.19
0.25
0.25
0.25
0.21
0.22
0.25
0.24

Olfr444
0.31
0.29
0.30
0.32
0.31
0.32
0.23
0.24
0.29
0.32

Olfr446
0.28
0.35
0.16
0.20
0.25
0.25
0.13
0.13
0.15
0.15

Olfr447
0.31
0.31
0.25
0.26
0.25
0.24
0.23
0.23
0.28
0.24

Olfr448
0.29
0.29
0.25
0.25
0.22
0.27
0.18
0.20
0.22
0.23

Olfr449
0.24
0.24
0.22
0.23
0.23
0.23
0.18
0.16
0.17
0.20

Olfr45
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr450
0.29
0.31
0.26
0.27
0.25
0.25
0.21
0.20
0.21
0.19

Olfr452
0.05
0.08
0.09
0.11
0.06
0.05
0.06
0.04
0.05
0.02

Olfr453
0.25
0.24
0.22
0.24
0.21
0.24
0.19
0.18
0.21
0.20

Olfr455
0.25
0.23
0.21
0.22
0.23
0.24
0.19
0.18
0.22
0.23

Olfr456
0.38
0.39
0.33
0.35
0.30
0.31
0.27
0.26
0.32
0.28

Olfr457
0.38
0.39
0.33
0.35
0.30
0.31
0.27
0.26
0.32
0.28

Olfr458
0.42
0.47
0.34
0.40
0.31
0.34
0.29
0.26
0.33
0.29

Olfr459
0.34
0.36
0.27
0.27
0.29
0.29
0.25
0.23
0.26
0.27

Olfr46
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr460
0.32
0.31
0.17
0.20
0.19
0.20
0.15
0.13
0.16
0.15

Olfr461
0.24
0.21
0.13
0.14
0.13
0.16
0.12
0.12
0.12
0.10

Olfr462
0.50
0.55
0.41
0.44
0.45
0.51
0.39
0.37
0.43
0.42

Olfr463
0.38
0.39
0.29
0.32
0.29
0.33
0.28
0.28
0.34
0.33

Olfr464
0.39
0.44
0.33
0.37
0.35
0.36
0.30
0.29
0.35
0.32

Olfr466
0.18
0.20
0.11
0.16
0.16
0.15
0.11
0.09
0.10
0.10

Olfr467
0.41
0.37
0.22
0.24
0.26
0.30
0.25
0.22
0.24
0.22

Olfr469
0.24
0.29
0.14
0.11
0.16
0.19
0.10
0.11
0.13
0.12

Olfr47
0.25
0.25
0.21
0.23
0.25
0.28
0.18
0.17
0.21
0.21

Olfr470
0.17
0.18
0.09
0.12
0.11
0.11
0.09
0.07
0.12
0.09

Olfr472
NA
0.03
NA
0.01
0.00
0.03
NA
NA
NA
NA

Olfr473
0.16
0.17
0.12
0.13
0.15
0.16
0.11
0.10
0.10
0.09

Olfr474
0.04
0.07
0.02
0.05
0.04
0.08
0.03
0.04
0.04
0.03

Olfr476
0.18
0.21
0.15
0.19
0.19
0.20
0.16
0.16
0.15
0.15

Olfr477
0.31
0.38
0.25
0.27
0.25
0.26
0.25
0.23
0.25
0.23

Olfr478
0.11
0.13
0.11
0.14
0.14
0.16
0.11
0.10
0.11
0.09

Olfr479
0.38
0.42
0.27
0.32
0.27
0.30
0.26
0.24
0.24
0.22

Olfr48
0.42
0.45
0.34
0.39
0.36
0.39
0.34
0.32
0.38
0.36

Olfr480
0.01
0.03
0.05
0.04
0.05
0.07
0.02
0.01
0.01
0.02

Olfr481
0.19
0.19
0.18
0.18
0.19
0.18
0.17
0.14
0.20
0.17

Olfr482
0.25
0.27
0.11
0.16
0.20
0.23
0.14
0.13
0.13
0.11

Olfr483
0.23
0.22
0.15
0.21
0.20
0.22
0.17
0.16
0.18
0.16

Olfr484
0.25
0.26
0.16
0.20
0.20
0.20
0.15
0.16
0.13
0.13

Olfr485
0.41
0.37
0.27
0.25
0.30
0.28
0.30
0.28
0.27
0.23

Olfr486
0.24
0.29
0.19
0.20
0.19
0.23
0.20
0.17
0.20
0.18

Olfr487
0.24
0.29
0.19
0.20
0.19
0.23
0.20
0.17
0.20
0.18

Olfr488
0.18
0.24
0.09
0.12
0.12
0.13
0.15
0.14
0.14
0.10

Olfr49
0.21
0.28
0.16
0.15
0.19
0.19
0.16
0.12
0.17
0.17

Olfr490
0.12
0.21
0.03
0.08
0.04
0.05
0.03
0.00
NA
NA

Olfr491
0.21
0.24
0.20
0.20
0.18
0.19
0.17
0.16
0.18
0.15

Olfr492
0.22
0.21
0.12
0.15
0.18
0.16
0.16
0.14
0.11
0.11

Olfr493
0.09
0.13
0.10
0.09
0.13
0.10
0.12
0.09
0.09
0.10

Olfr494
0.26
0.27
0.14
0.18
0.17
0.19
0.16
0.14
0.17
0.17

Olfr495
0.15
0.28
0.12
0.18
0.16
0.15
0.11
0.10
0.12
0.10

Olfr497
0.18
0.24
0.11
0.13
0.13
0.14
0.11
0.12
0.12
0.08

Olfr498
0.13
0.15
0.13
0.15
0.13
0.14
0.13
0.10
0.07
0.08

Olfr5
0.30
0.29
0.26
0.27
0.24
0.26
0.24
0.23
0.32
0.27

Olfr50
0.16
0.20
0.12
0.10
0.09
0.15
0.06
0.05
0.09
0.05

Olfr502
0.18
0.19
0.18
0.20
0.18
0.19
0.14
0.15
0.15
0.14

Olfr503
0.28
0.32
0.23
0.24
0.22
0.25
0.20
0.20
0.23
0.22

Olfr504
0.21
0.25
0.11
0.16
0.17
0.16
0.08
0.07
0.09
0.08

Olfr506
0.25
0.27
0.11
0.16
0.20
0.23
0.14
0.13
0.13
0.11

Olfr507
0.25
0.27
0.11
0.16
0.20
0.23
0.14
0.13
0.13
0.11

Olfr508
0.17
0.16
0.14
0.15
0.18
0.21
0.12
0.11
0.16
0.11

Olfr509
0.13
0.24
0.08
0.11
0.13
0.13
0.05
0.05
0.09
0.09

Olfr51
0.30
0.32
0.27
0.31
0.28
0.34
0.32
0.30
0.30
0.24

Olfr510
0.10
0.17
0.11
0.10
0.18
0.19
0.10
0.12
0.11
0.10

Olfr512
0.10
0.17
0.04
0.11
0.09
0.10
0.03
0.03
0.02
0.03

Olfr513
0.34
0.39
0.24
0.30
0.30
0.33
0.22
0.21
0.23
0.20

Olfr514
0.37
0.40
0.26
0.29
0.30
0.30
0.23
0.21
0.25
0.25

Olfr516
0.06
0.13
0.08
0.07
0.10
0.07
0.04
0.03
0.12
0.07

Olfr517
0.27
0.28
0.21
0.27
0.25
0.21
0.18
0.15
0.22
0.18

Olfr518
0.23
0.28
0.09
0.14
0.13
0.15
0.14
0.10
0.12
0.09

Olfr519
0.23
0.28
0.09
0.14
0.13
0.15
0.14
0.10
0.12
0.09

Olfr52
0.23
0.24
0.18
0.22
0.24
0.29
0.19
0.19
0.21
0.19

Olfr520
0.25
0.27
0.20
0.25
0.23
0.24
0.18
0.17
0.20
0.21

Olfr521
0.14
0.23
0.16
0.16
0.20
0.26
0.15
0.10
0.18
0.13

Olfr522
0.45
0.45
0.36
0.38
0.35
0.36
0.32
0.30
0.36
0.38

Olfr523
0.42
0.42
0.32
0.35
0.29
0.30
0.30
0.29
0.34
0.31

Olfr524
0.51
0.52
0.47
0.47
0.43
0.49
0.39
0.39
0.48
0.46

Olfr525
0.31
0.35
0.22
0.23
0.26
0.27
0.19
0.19
0.24
0.23

Olfr527
0.27
0.26
0.29
0.31
0.30
0.30
0.23
0.24
0.25
0.29

Olfr53
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr530
0.42
0.43
0.32
0.36
0.31
0.36
0.30
0.28
0.32
0.28

Olfr531
0.14
0.13
0.19
0.18
0.20
0.29
0.15
0.15
0.19
0.19

Olfr532
0.33
0.36
0.24
0.33
0.27
0.32
0.24
0.22
0.26
0.25

Olfr533
0.42
0.43
0.32
0.36
0.31
0.36
0.30
0.28
0.32
0.28

Olfr535
0.44
0.46
0.40
0.40
0.38
0.42
0.37
0.38
0.41
0.36

Olfr536
0.42
0.43
0.32
0.36
0.31
0.36
0.30
0.28
0.32
0.28

Olfr538
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr539
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr54
0.58
0.55
0.40
0.45
0.42
0.43
0.37
0.35
0.43
0.38

Olfr541
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr543
0.45
0.47
0.37
0.37
0.41
0.40
0.34
0.33
0.41
0.37

Olfr544
0.20
0.20
0.22
0.22
0.23
0.23
0.16
0.15
0.22
0.23

Olfr545
0.50
0.49
0.43
0.48
0.42
0.43
0.38
0.38
0.45
0.40

Olfr547
0.20
0.19
0.16
0.17
0.17
0.19
0.12
0.12
0.18
0.16

Olfr549
0.42
0.44
0.30
0.35
0.35
0.35
0.28
0.26
0.33
0.31

Olfr55
0.51
0.58
0.27
0.27
0.31
0.31
0.25
0.24
0.31
0.27

Olfr550
0.38
0.41
0.34
0.34
0.33
0.35
0.30
0.28
0.36
0.33

Olfr551
0.22
0.19
0.20
0.23
0.22
0.23
0.19
0.19
0.21
0.19

Olfr552
0.26
0.30
0.25
0.26
0.22
0.22
0.19
0.19
0.24
0.19

Olfr553
0.23
0.21
0.19
0.20
0.20
0.19
0.19
0.18
0.23
0.18

Olfr554
0.25
0.27
0.21
0.21
0.19
0.22
0.22
0.20
0.20
0.24

Olfr555
0.27
0.25
0.27
0.28
0.28
0.32
0.23
0.21
0.24
0.21

Olfr556
0.23
0.26
0.20
0.20
0.22
0.23
0.19
0.17
0.20
0.20

Olfr557
0.21
0.25
0.17
0.21
0.16
0.18
0.16
0.15
0.19
0.17

Olfr558
0.29
0.31
0.22
0.28
0.25
0.27
0.24
0.24
0.25
0.24

Olfr559
0.31
0.37
0.10
0.17
0.21
0.20
0.16
0.14
0.13
0.12

Olfr56
0.45
0.55
0.37
0.78
0.35
0.52
0.53
0.30
0.26
0.21

Olfr560
0.11
0.11
0.08
0.10
0.10
0.13
0.08
0.07
0.11
0.08

Olfr561
0.13
0.15
0.13
0.16
0.14
0.14
0.14
0.13
0.13
0.12

Olfr564
0.16
0.17
0.10
0.10
0.10
0.07
0.07
0.07
0.10
0.07

Olfr566
0.53
0.54
0.37
0.38
0.40
0.45
0.31
0.29
0.39
0.29

Olfr568
0.20
0.22
0.18
0.18
0.21
0.24
0.17
0.18
0.15
0.16

Olfr569
0.27
0.30
0.18
0.24
0.22
0.23
0.17
0.17
0.21
0.16

Olfr57
0.15
0.32
0.09
0.11
0.15
0.21
0.08
0.06
0.09
0.06

Olfr570
0.14
0.14
0.14
0.14
0.12
0.13
0.11
0.11
0.13
0.09

Olfr571
0.28
0.32
0.21
0.27
0.25
0.26
0.25
0.22
0.24
0.22

Olfr572
0.30
0.30
0.23
0.24
0.21
0.26
0.19
0.19
0.23
0.20

Olfr574
0.24
0.26
0.17
0.22
0.16
0.17
0.16
0.14
0.17
0.17

Olfr575
0.21
0.23
0.15
0.19
0.18
0.21
0.17
0.15
0.18
0.16

Olfr576
0.24
0.27
0.21
0.26
0.18
0.21
0.20
0.17
0.20
0.18

Olfr577
0.27
0.30
0.22
0.25
0.22
0.25
0.21
0.21
0.24
0.21

Olfr578
0.10
0.12
0.12
0.12
0.13
0.15
0.08
0.09
0.10
0.08

Olfr58
0.03
0.08
0.02
0.06
0.10
0.11
0.03
0.00
0.01
NA

Olfr582
0.40
0.41
0.26
0.26
0.28
0.29
0.25
0.23
0.26
0.25

Olfr583
0.10
0.10
0.07
0.09
0.13
0.13
0.06
0.05
0.06
0.06

Olfr584
0.21
0.21
0.15
0.15
0.19
0.18
0.15
0.13
0.15
0.14

Olfr585
0.10
0.10
0.07
0.09
0.13
0.13
0.06
0.05
0.06
0.06

Olfr586
0.34
0.36
0.24
0.27
0.22
0.25
0.23
0.20
0.22
0.21

Olfr589
0.22
0.29
0.21
0.20
0.27
0.27
0.19
0.17
0.19
0.22

Olfr59
0.34
0.36
0.27
0.27
0.25
0.28
0.20
0.19
0.27
0.26

Olfr591
0.15
0.16
0.13
0.18
0.18
0.21
0.16
0.15
0.13
0.12

Olfr592
0.13
0.19
0.09
0.12
0.14
0.15
0.12
0.10
0.09
0.08

Olfr593
0.26
0.26
0.20
0.20
0.20
0.24
0.17
0.14
0.18
0.15

Olfr594
0.37
0.38
0.21
0.24
0.23
0.21
0.18
0.16
0.22
0.19

Olfr596
0.22
0.21
0.17
0.18
0.19
0.20
0.17
0.17
0.14
0.14

Olfr597
0.08
0.05
0.02
0.03
0.19
0.07
0.04
0.03
0.05
0.02

Olfr598
0.15
0.14
0.21
0.24
0.26
0.32
0.16
0.16
0.22
0.20

Olfr599
0.19
0.23
0.12
0.15
0.14
0.18
0.15
0.12
0.16
0.12

Olfr6
0.24
0.26
0.24
0.22
0.25
0.26
0.21
0.20
0.24
0.25

Olfr60
0.16
0.20
0.14
0.11
0.19
0.22
0.07
0.07
0.14
0.11

Olfr600
0.18
0.17
0.13
0.16
0.15
0.17
0.11
0.10
0.13
0.13

Olfr601
0.36
0.36
0.34
0.33
0.33
0.31
0.27
0.26
0.32
0.29

Olfr603
0.22
0.30
0.17
0.20
0.20
0.20
0.14
0.12
0.19
0.16

Olfr605
0.30
0.34
0.26
0.25
0.22
0.29
0.21
0.23
0.30
0.23

Olfr606
0.12
0.13
0.10
0.11
0.11
0.11
0.13
0.11
0.11
0.09

Olfr607
0.13
0.12
0.15
0.18
0.18
0.22
0.13
0.12
0.15
0.16

Olfr608
0.38
0.37
0.31
0.36
0.30
0.33
0.26
0.25
0.29
0.30

Olfr609
0.34
0.37
0.31
0.35
0.31
0.35
0.27
0.26
0.30
0.26

Olfr61
0.42
0.45
0.31
0.26
0.29
0.26
0.28
0.27
0.27
0.26

Olfr610
0.36
0.38
0.27
0.32
0.32
0.34
0.27
0.26
0.29
0.28

Olfr611
0.20
0.25
0.23
0.25
0.20
0.19
0.17
0.13
0.18
0.14

Olfr612
0.15
0.20
0.12
0.15
0.14
0.19
0.09
0.09
0.14
0.09

Olfr613
0.16
0.19
0.16
0.18
0.16
0.19
0.11
0.11
0.11
0.12

Olfr615
0.19
0.22
0.19
0.25
0.20
0.22
0.14
0.13
0.17
0.14

Olfr616
0.22
0.24
0.16
0.20
0.20
0.24
0.17
0.15
0.17
0.14

Olfr617
0.22
0.22
0.11
0.17
0.14
0.11
0.12
0.10
0.11
0.09

Olfr618
0.12
0.09
0.07
0.09
0.07
0.10
0.08
0.07
0.05
0.04

Olfr619
0.11
0.13
0.10
0.11
0.14
0.13
0.11
0.10
0.09
0.07

Olfr62
0.24
0.25
0.20
0.24
0.23
0.26
0.20
0.16
0.20
0.21

Olfr620
0.13
0.14
0.15
0.14
0.18
0.16
0.18
0.16
0.17
0.15

Olfr622
0.17
0.24
0.13
0.14
0.18
0.18
0.16
0.15
0.15
0.11

Olfr623
0.25
0.25
0.15
0.22
0.20
0.22
0.12
0.12
0.12
0.13

Olfr624
0.04
0.02
0.07
0.06
0.12
0.11
0.17
0.05
0.06
0.03

Olfr628
0.08
0.10
0.06
0.08
0.08
0.06
0.02
0.02
0.03
0.01

Olfr629
0.13
0.11
0.15
0.14
0.16
0.18
0.09
0.09
0.13
0.10

Olfr63
0.42
0.44
0.35
0.35
0.35
0.39
0.31
0.30
0.32
0.33

Olfr630
0.18
0.17
0.08
0.10
0.15
0.17
0.08
0.06
0.07
0.06

Olfr631
0.15
0.18
0.09
0.08
0.11
0.09
0.06
0.05
0.08
0.08

Olfr632
0.37
0.38
0.32
0.33
0.31
0.33
0.29
0.26
0.32
0.31

Olfr633
0.28
0.31
0.25
0.25
0.24
0.25
0.23
0.24
0.26
0.28

Olfr635
0.28
0.30
0.19
0.24
0.23
0.27
0.23
0.20
0.22
0.20

Olfr638
0.32
0.32
0.28
0.26
0.26
0.31
0.24
0.24
0.27
0.24

Olfr639
0.22
0.23
0.16
0.17
0.19
0.21
0.14
0.13
0.14
0.15

Olfr64
0.20
0.22
0.17
0.19
0.21
0.26
0.16
0.15
0.18
0.15

Olfr640
0.19
0.25
0.18
0.23
0.16
0.19
0.14
0.13
0.19
0.13

Olfr641
0.28
0.34
0.23
0.23
0.20
0.22
0.22
0.21
0.20
0.17

Olfr642
0.34
0.33
0.24
0.26
0.23
0.24
0.25
0.23
0.23
0.22

Olfr643
0.13
0.12
0.07
0.10
0.07
0.09
0.07
0.06
0.08
0.08

Olfr644
0.31
0.28
0.20
0.22
0.21
0.21
0.20
0.19
0.18
0.18

Olfr645
0.27
0.29
0.27
0.28
0.24
0.25
0.25
0.22
0.24
0.22

Olfr646
0.37
0.34
0.28
0.30
0.30
0.33
0.26
0.27
0.27
0.26

Olfr648
0.24
0.27
0.22
0.25
0.24
0.24
0.20
0.20
0.24
0.22

Olfr649
0.19
0.23
0.18
0.21
0.17
0.22
0.16
0.15
0.16
0.15

Olfr65
0.19
0.19
0.11
0.13
0.13
0.19
0.10
0.08
0.12
0.12

Olfr651
0.22
0.30
0.19
0.24
0.23
0.25
0.21
0.20
0.22
0.22

Olfr652
0.23
0.27
0.18
0.23
0.22
0.24
0.22
0.19
0.19
0.19

Olfr653
0.32
0.35
0.26
0.30
0.30
0.31
0.23
0.22
0.25
0.23

Olfr654
0.16
0.24
0.14
0.18
0.15
0.16
0.14
0.13
0.13
0.11

Olfr655
0.15
0.17
0.19
0.16
0.17
0.17
0.17
0.15
0.17
0.16

Olfr656
0.35
0.33
0.28
0.27
0.28
0.31
0.24
0.23
0.28
0.24

Olfr657
0.28
0.27
0.23
0.25
0.23
0.27
0.22
0.21
0.23
0.20

Olfr658
0.35
0.39
0.30
0.34
0.35
0.38
0.28
0.26
0.35
0.30

Olfr659
0.22
0.25
0.16
0.18
0.17
0.18
0.14
0.12
0.13
0.13

Olfr66
0.13
0.11
0.08
0.13
0.11
0.14
0.09
0.08
0.09
0.09

Olfr661
0.28
0.28
0.19
0.19
0.20
0.23
0.17
0.15
0.18
0.16

Olfr663
0.17
0.18
0.14
0.16
0.14
0.17
0.16
0.14
0.15
0.14

Olfr665
0.11
0.13
0.12
0.13
0.09
0.11
0.05
0.06
0.07
0.05

Olfr666
0.37
0.34
0.27
0.30
0.23
0.28
0.20
0.19
0.23
0.18

Olfr667
0.28
0.28
0.20
0.24
0.23
0.25
0.19
0.18
0.22
0.18

Olfr668
0.11
0.13
0.09
0.11
0.12
0.13
0.08
0.06
0.10
0.09

Olfr669
0.29
0.29
0.26
0.28
0.26
0.27
0.25
0.21
0.27
0.26

Olfr67
0.08
0.09
0.09
0.12
0.07
0.07
0.05
0.03
0.05
0.04

Olfr670
0.23
0.23
0.17
0.19
0.20
0.24
0.22
0.21
0.21
0.18

Olfr671
0.18
0.23
0.15
0.13
0.12
0.14
0.15
0.13
0.16
0.15

Olfr672
0.26
0.27
0.14
0.16
0.14
0.15
0.13
0.10
0.13
0.13

Olfr675
0.09
0.09
0.11
0.13
0.13
0.13
0.08
0.07
0.10
0.08

Olfr676
0.11
0.12
0.09
0.11
0.11
0.11
0.11
0.10
0.10
0.08

Olfr677
0.14
0.18
0.10
0.15
0.13
0.15
0.11
0.10
0.11
0.08

Olfr678
0.44
0.46
0.34
0.37
0.37
0.40
0.31
0.30
0.35
0.32

Olfr679
0.13
0.16
0.10
0.15
0.15
0.16
0.12
0.09
0.09
0.09

Olfr68
0.19
0.20
0.15
0.18
0.17
0.14
0.15
0.12
0.14
0.11

Olfr681
0.13
0.16
0.10
0.15
0.15
0.16
0.12
0.09
0.09
0.09

Olfr683
0.16
0.20
0.14
0.17
0.15
0.13
0.11
0.10
0.11
0.15

Olfr684
0.19
0.19
0.11
0.14
0.21
0.23
0.11
0.09
0.10
0.07

Olfr685
0.21
0.24
0.21
0.20
0.20
0.25
0.20
0.18
0.19
0.20

Olfr686
0.33
0.33
0.26
0.28
0.25
0.26
0.23
0.22
0.30
0.27

Olfr688
0.26
0.25
0.16
0.18
0.20
0.24
0.15
0.14
0.15
0.15

Olfr689
0.34
0.35
0.24
0.27
0.27
0.28
0.22
0.21
0.24
0.22

Olfr69
0.08
0.08
0.07
0.03
0.08
0.08
0.03
0.02
0.02
0.02

Olfr690
0.31
0.36
0.26
0.26
0.29
0.29
0.21
0.21
0.24
0.22

Olfr691
0.22
0.24
0.22
0.25
0.24
0.26
0.20
0.19
0.23
0.21

Olfr692
0.31
0.33
0.25
0.26
0.26
0.25
0.23
0.23
0.24
0.24

Olfr693
0.25
0.26
0.20
0.24
0.22
0.23
0.20
0.19
0.23
0.23

Olfr694
0.25
0.25
0.20
0.23
0.21
0.21
0.19
0.18
0.20
0.19

Olfr695
0.17
0.19
0.14
0.15
0.17
0.14
0.12
0.12
0.13
0.15

Olfr697
0.25
0.28
0.22
0.25
0.25
0.25
0.23
0.23
0.22
0.21

Olfr698
0.26
0.34
0.23
0.28
0.23
0.24
0.20
0.18
0.22
0.21

Olfr699
0.18
0.22
0.16
0.20
0.19
0.21
0.16
0.15
0.17
0.15

Olfr70
0.37
0.37
0.32
0.32
0.31
0.32
0.30
0.28
0.35
0.33

Olfr700
0.27
0.30
0.22
0.23
0.23
0.27
0.17
0.19
0.18
0.18

Olfr701
0.15
0.15
0.11
0.15
0.14
0.19
0.07
0.06
0.09
0.09

Olfr702
0.15
0.17
0.09
0.12
0.14
0.14
0.07
0.07
0.08
0.06

Olfr703
0.25
0.28
0.18
0.20
0.20
0.19
0.16
0.14
0.18
0.17

Olfr704
0.15
0.16
0.15
0.19
0.15
0.18
0.11
0.12
0.15
0.09

Olfr705
0.15
0.16
0.13
0.16
0.15
0.18
0.13
0.12
0.17
0.13

Olfr706
0.27
0.29
0.21
0.19
0.22
0.20
0.20
0.18
0.17
0.19

Olfr707
0.10
0.13
0.09
0.16
0.24
0.20
0.10
0.08
0.13
0.09

Olfr71
0.51
0.52
0.44
0.47
0.47
0.49
0.42
0.40
0.51
0.48

Olfr710
0.27
0.28
0.22
0.24
0.24
0.27
0.23
0.22
0.24
0.22

Olfr711
0.27
0.28
0.23
0.25
0.24
0.23
0.20
0.19
0.27
0.24

Olfr713
0.34
0.36
0.31
0.31
0.31
0.36
0.23
0.23
0.27
0.26

Olfr714
0.29
0.20
0.22
0.21
0.23
0.24
0.23
0.23
0.31
0.26

Olfr715
0.16
0.19
0.06
0.11
0.09
0.10
0.10
0.08
0.09
0.08

Olfr716
0.20
0.21
0.16
0.19
0.17
0.16
0.14
0.13
0.16
0.15

Olfr720
0.24
0.28
0.15
0.19
0.18
0.21
0.18
0.16
0.19
0.17

Olfr722
0.02
0.09
0.03
0.06
0.05
0.08
0.01
NA
0.01
0.00

Olfr723
0.35
0.33
0.24
0.26
0.28
0.26
0.22
0.22
0.22
0.22

Olfr724
0.35
0.33
0.24
0.26
0.28
0.26
0.22
0.22
0.22
0.22

Olfr725
0.15
0.20
0.14
0.14
0.19
0.18
0.09
0.07
0.14
0.11

Olfr726
0.16
0.17
0.11
0.14
0.16
0.17
0.05
0.06
0.10
0.07

Olfr727
0.06
0.07
0.06
0.07
0.11
0.09
0.08
0.05
0.06
0.05

Olfr728
0.15
0.17
0.13
0.14
0.16
0.16
0.15
0.14
0.16
0.12

Olfr729
0.13
0.13
0.08
0.09
0.12
0.13
0.09
0.07
0.05
0.08

Olfr73
0.25
0.27
0.15
0.19
0.22
0.25
0.16
0.14
0.20
0.19

Olfr730
0.19
0.22
0.16
0.16
0.20
0.21
0.14
0.13
0.12
0.12

Olfr731
0.08
0.10
0.09
0.10
0.16
0.16
0.11
0.10
0.11
0.07

Olfr732
0.10
0.14
0.09
0.12
0.10
0.10
0.13
0.12
0.10
0.08

Olfr733
0.14
0.14
0.12
0.12
0.10
0.09
0.13
0.10
0.16
0.09

Olfr734
0.22
0.23
0.21
0.20
0.19
0.17
0.19
0.17
0.30
0.22

Olfr735
0.20
0.23
0.18
0.18
0.18
0.16
0.14
0.14
0.24
0.16

Olfr736
0.25
0.28
0.22
0.25
0.19
0.21
0.20
0.18
0.23
0.20

Olfr738
0.24
0.28
0.20
0.22
0.22
0.25
0.19
0.19
0.17
0.18

Olfr739
0.05
0.14
0.02
0.03
0.01
0.03
0.01
NA
0.03
NA

Olfr74
0.20
0.20
0.16
0.18
0.17
0.15
0.13
0.13
0.17
0.14

Olfr740
0.21
0.21
0.18
0.21
0.19
0.20
0.14
0.12
0.19
0.17

Olfr741
0.23
0.23
0.17
0.21
0.24
0.24
0.15
0.15
0.17
0.16

Olfr742
0.07
0.17
0.04
0.06
0.07
0.04
0.02
0.01
0.00
NA

Olfr743
0.21
0.29
0.23
0.20
0.19
0.20
0.11
0.10
0.12
0.10

Olfr744
0.31
0.25
0.24
0.29
0.30
0.29
0.26
0.21
0.25
0.26

Olfr745
0.36
0.38
0.26
0.28
0.28
0.28
0.26
0.23
0.27
0.26

Olfr746
0.14
0.15
0.10
0.10
0.14
0.16
0.08
0.08
0.06
0.06

Olfr747
0.03
0.08
0.03
0.07
0.13
0.13
0.02
0.03
0.02
0.02

Olfr748
0.13
0.15
0.06
0.08
0.11
0.12
0.09
0.07
0.11
0.05

Olfr749
0.06
0.06
0.06
0.07
0.09
0.10
0.03
0.03
0.03
0.04

Olfr750
0.38
0.40
0.27
0.28
0.31
0.34
0.26
0.25
0.29
0.27

Olfr76
0.30
0.35
0.22
0.22
0.22
0.25
0.18
0.19
0.24
0.25

Olfr761
0.15
0.22
0.15
0.17
0.15
0.15
0.10
0.10
0.11
0.09

Olfr763
0.31
0.30
0.19
0.20
0.21
0.23
0.17
0.15
0.18
0.18

Olfr765
0.35
0.33
0.27
0.29
0.24
0.25
0.24
0.20
0.26
0.28

Olfr767
0.51
0.50
0.31
0.36
0.30
0.35
0.53
0.53
0.56
0.58

Olfr768
0.02
NA
0.02
0.05
0.07
0.10
0.01
0.00
0.04
0.02

Olfr769
0.28
0.29
0.17
0.22
0.22
0.25
0.14
0.14
0.18
0.16

Olfr77
0.16
0.20
0.09
0.11
0.11
0.11
0.09
0.08
0.11
0.09

Olfr770
0.30
0.30
0.22
0.25
0.22
0.24
0.23
0.21
0.23
0.22

Olfr771
0.11
0.12
0.05
0.08
0.12
0.12
0.05
0.05
0.09
0.08

Olfr772
0.07
0.08
0.06
0.08
0.06
0.08
0.05
0.04
0.04
0.04

Olfr773
0.17
0.18
0.14
0.11
0.15
0.16
0.15
0.12
0.09
0.10

Olfr774
0.35
0.37
0.27
0.30
0.28
0.29
0.28
0.25
0.28
0.25

Olfr775
0.13
0.15
0.08
0.12
0.15
0.14
0.11
0.10
0.09
0.08

Olfr776
0.15
0.24
0.05
0.07
0.09
0.17
0.07
0.04
0.04
0.01

Olfr777
0.08
0.10
0.06
0.07
0.10
0.08
0.06
0.07
0.06
0.07

Olfr78
0.11
0.11
0.08
0.10
0.10
0.13
0.08
0.07
0.11
0.08

Olfr780
0.10
0.14
0.11
0.16
0.12
0.14
0.10
0.09
0.12
0.11

Olfr781
0.09
0.10
0.06
0.10
0.08
0.09
0.04
0.04
0.06
0.04

Olfr782
0.12
0.18
0.08
0.15
0.18
0.20
0.09
0.07
0.11
0.10

Olfr784
0.25
0.34
0.16
0.19
0.21
0.27
0.13
0.14
0.16
0.15

Olfr786
0.19
0.27
0.10
0.12
0.09
0.08
0.07
0.07
0.08
0.08

Olfr787
0.04
0.07
0.03
0.01
0.11
0.13
0.06
0.05
0.02
0.02

Olfr788
0.35
0.34
0.23
0.22
0.21
0.22
0.15
0.15
0.20
0.17

Olfr790
0.26
0.29
0.21
0.27
0.22
0.24
0.16
0.16
0.20
0.16

Olfr791
0.14
0.17
0.11
0.13
0.08
0.11
0.06
0.06
0.10
0.09

Olfr792
0.06
0.04
0.03
0.10
0.09
0.04
0.06
0.04
0.04
0.05

Olfr794
0.23
0.22
0.17
0.18
0.20
0.19
0.13
0.12
0.15
0.16

Olfr796
0.42
0.45
0.32
0.34
0.35
0.36
0.27
0.25
0.31
0.30

Olfr798
0.03
0.12
0.08
0.07
0.15
0.14
0.04
0.03
0.02
0.04

Olfr799
0.12
0.21
0.12
0.12
0.13
0.14
0.08
0.07
0.09
0.08

Olfr8
0.13
0.16
0.03
0.06
0.06
0.08
0.01
0.01
0.04
0.01

Olfr800
0.08
0.10
0.06
0.07
0.10
0.08
0.06
0.07
0.06
0.07

Olfr801
0.25
0.28
0.14
0.18
0.19
0.19
0.11
0.12
0.16
0.12

Olfr802
0.14
0.21
0.11
0.08
0.10
0.10
0.08
0.07
0.07
0.06

Olfr803
0.12
0.16
0.10
0.08
0.12
0.10
0.02
0.05
0.02
0.03

Olfr804
0.12
0.18
0.08
0.15
0.18
0.20
0.09
0.07
0.11
0.10

Olfr805
0.12
0.15
0.10
0.10
0.10
0.12
0.08
0.07
0.08
0.07

Olfr806
0.06
0.13
NA
NA
0.04
0.04
NA
NA
NA
NA

Olfr807
0.39
0.40
0.31
0.33
0.33
0.36
0.28
0.26
0.30
0.30

Olfr808
0.15
0.21
0.14
0.20
0.17
0.19
0.14
0.13
0.15
0.13

Olfr809
0.07
0.08
0.04
0.07
0.07
0.08
0.01
0.03
0.05
0.03

Olfr810
0.32
0.33
0.21
0.23
0.21
0.24
0.19
0.18
0.22
0.21

Olfr811
0.24
0.25
0.21
0.23
0.24
0.25
0.13
0.15
0.17
0.15

Olfr812
0.25
0.29
0.17
0.19
0.16
0.18
0.15
0.13
0.14
0.14

Olfr813
0.12
0.15
0.10
0.13
0.08
0.07
0.06
0.07
0.08
0.08

Olfr814
0.03
0.07
0.06
0.05
0.08
0.14
NA
NA
0.01
0.01

Olfr815
0.06
0.07
0.02
0.04
0.05
0.08
0.00
NA
0.02
0.00

Olfr816
0.08
0.13
0.07
0.07
0.09
0.10
0.04
0.04
0.04
0.03

Olfr818
0.20
0.30
0.13
0.13
0.15
0.16
0.09
0.09
0.10
0.07

Olfr819
0.46
0.48
0.29
0.31
0.28
0.31
0.28
0.26
0.28
0.23

Olfr820
0.10
0.14
0.12
0.10
0.09
0.10
0.05
0.05
0.05
0.05

Olfr821
0.14
0.14
0.12
0.11
0.13
0.13
0.12
0.10
0.11
0.10

Olfr822
0.14
0.14
0.11
0.13
0.11
0.11
0.07
0.07
0.08
0.06

Olfr823
0.10
0.19
0.05
0.08
0.09
0.08
0.07
0.04
0.04
0.05

Olfr824
0.10
0.19
0.05
0.08
0.09
0.08
0.07
0.04
0.04
0.05

Olfr825
0.22
0.25
0.15
0.18
0.21
0.21
0.13
0.11
0.13
0.13

Olfr826
0.07
0.11
0.07
0.06
0.09
0.08
0.01
NA
0.03
0.00

Olfr827
0.13
0.13
0.06
0.08
0.09
0.12
0.07
0.06
0.07
0.06

Olfr828
0.13
0.17
0.09
0.13
0.13
0.13
0.07
0.07
0.07
0.07

Olfr829
0.13
0.17
0.12
0.14
0.15
0.18
0.11
0.09
0.13
0.10

Olfr830
0.22
0.20
0.11
0.17
0.15
0.18
0.13
0.10
0.13
0.10

Olfr832
0.04
0.04
0.03
0.07
0.07
0.07
0.02
0.02
0.04
0.03

Olfr834
0.00
NA
0.02
0.04
0.08
0.12
NA
NA
0.01
NA

Olfr835
0.23
0.28
0.17
0.20
0.25
0.26
0.15
0.13
0.16
0.18

Olfr836
0.13
0.23
0.05
0.07
0.06
0.06
0.03
0.01
0.02
0.04

Olfr837
0.01
0.03
0.02
0.03
0.07
0.09
0.02
NA
0.02
0.02

Olfr843
0.17
0.19
0.14
0.17
0.15
0.15
0.17
0.15
0.12
0.12

Olfr845
0.20
0.20
0.22
0.19
0.19
0.20
0.14
0.12
0.14
0.13

Olfr846
NA
0.02
0.02
0.03
0.04
0.05
0.01
NA
0.02
0.01

Olfr847
0.11
0.14
0.02
0.10
0.10
0.11
0.03
0.03
0.04
0.05

Olfr849
0.08
0.11
0.05
0.04
0.03
0.05
0.01
0.01
NA
0.00

Olfr850
0.28
0.34
0.20
0.22
0.19
0.21
0.17
0.14
0.17
0.14

Olfr851
0.17
0.20
0.13
0.14
0.16
0.17
0.08
0.08
0.08
0.11

Olfr853
0.11
0.14
0.08
0.13
0.11
0.11
0.07
0.06
0.09
0.07

Olfr854
0.10
0.14
0.06
0.10
0.11
0.11
0.05
0.06
0.06
0.05

Olfr855
0.09
0.15
0.07
0.10
0.13
0.15
0.09
0.09
0.08
0.09

Olfr856-ps1
0.26
0.25
0.18
0.21
0.16
0.21
0.15
0.12
0.14
0.13

Olfr857
0.11
0.14
0.11
0.15
0.10
0.16
0.08
0.07
0.07
0.04

Olfr859
0.05
0.04
0.01
0.11
0.07
0.07
0.03
0.03
0.02
0.04

Olfr860
0.03
0.06
0.07
0.07
0.08
0.09
0.05
0.04
0.05
0.06

Olfr862
0.12
0.13
0.13
0.14
0.15
0.22
0.10
0.08
0.10
0.08

Olfr866
0.09
0.13
0.12
0.12
0.13
0.11
0.07
0.06
0.10
0.07

Olfr867
0.26
0.28
0.20
0.18
0.24
0.21
0.19
0.17
0.22
0.19

Olfr868
0.04
0.06
0.05
0.07
0.07
0.07
0.03
0.02
0.03
0.03

Olfr869
0.03
0.05
0.03
0.06
0.11
0.09
0.03
0.03
0.06
0.03

Olfr870
0.25
0.25
0.14
0.18
0.17
0.20
0.14
0.14
0.17
0.17

Olfr871
0.23
0.25
0.20
0.21
0.19
0.25
0.14
0.13
0.16
0.14

Olfr872
0.09
0.10
0.02
0.02
0.09
0.09
0.01
0.01
0.00
0.01

Olfr873
0.20
0.22
0.06
0.11
0.09
0.08
0.06
0.05
0.08
0.07

Olfr874
0.32
0.37
0.24
0.27
0.26
0.25
0.22
0.22
0.25
0.24

Olfr875
0.26
0.32
0.16
0.18
0.21
0.24
0.14
0.15
0.17
0.15

Olfr876
0.20
0.23
0.19
0.19
0.17
0.21
0.15
0.14
0.18
0.14

Olfr877
0.18
0.23
0.11
0.15
0.13
0.14
0.12
0.09
0.12
0.09

Olfr878
0.25
0.28
0.21
0.24
0.19
0.21
0.18
0.17
0.20
0.18

Olfr881
0.14
0.12
0.06
0.08
0.10
0.11
0.09
0.08
0.07
0.07

Olfr883
0.12
0.13
0.06
0.08
0.09
0.12
0.08
0.06
0.05
0.04

Olfr884
0.12
0.13
0.06
0.08
0.09
0.12
0.08
0.06
0.05
0.04

Olfr885
0.12
0.13
0.06
0.08
0.09
0.12
0.08
0.06
0.05
0.04

Olfr887
0.12
0.13
0.06
0.08
0.09
0.12
0.08
0.06
0.05
0.04

Olfr888
0.10
0.10
0.05
0.07
0.05
0.06
0.06
0.05
0.07
0.05

Olfr889
0.06
0.08
0.03
0.07
0.12
0.13
0.03
0.04
0.03
0.04

Olfr890
0.03
0.05
0.04
0.06
0.07
0.07
0.03
0.04
0.05
0.03

Olfr891
0.16
0.18
0.14
0.12
0.13
0.12
0.11
0.09
0.09
0.08

Olfr893
0.08
0.10
0.07
0.05
0.07
0.09
0.07
0.05
0.05
0.05

Olfr894
0.09
0.06
0.05
0.07
0.06
0.10
0.06
0.05
0.07
0.04

Olfr895
0.05
0.12
0.05
0.08
0.07
0.07
0.04
0.04
0.05
0.02

Olfr898
0.32
0.35
0.18
0.20
0.21
0.19
0.19
0.18
0.21
0.17

Olfr899
0.18
0.24
0.13
0.17
0.15
0.15
0.13
0.11
0.13
0.12

Olfr9
0.23
0.27
0.10
0.13
0.16
0.16
0.09
0.10
0.13
0.14

Olfr90
0.30
0.31
0.21
0.25
0.17
0.18
0.17
0.16
0.21
0.16

Olfr900
0.17
0.20
0.13
0.16
0.17
0.20
0.13
0.11
0.13
0.11

Olfr901
0.30
0.27
0.22
0.24
0.22
0.23
0.19
0.17
0.22
0.20

Olfr902
0.22
0.26
0.19
0.20
0.23
0.25
0.14
0.14
0.17
0.16

Olfr904
0.10
0.14
0.06
0.07
0.08
0.09
0.03
0.02
0.04
0.03

Olfr905
0.15
0.19
0.01
0.06
0.09
0.10
0.03
0.02
0.06
0.03

Olfr906
0.14
0.21
0.10
0.12
0.15
0.13
0.10
0.08
0.11
0.07

Olfr907
0.11
0.11
0.08
0.12
0.10
0.09
0.08
0.07
0.09
0.08

Olfr908
0.12
0.15
0.05
0.06
0.11
0.14
0.07
0.06
0.09
0.04

Olfr91
0.63
0.63
0.43
0.46
0.45
0.46
0.38
0.38
0.44
0.43

Olfr910
0.03
0.05
0.04
0.08
0.04
0.03
0.02
0.02
0.04
0.01

Olfr911-ps1
0.08
0.12
0.07
0.08
0.07
0.07
0.06
0.04
0.04
0.02

Olfr912
0.09
0.17
0.06
0.08
0.08
0.12
0.02
0.02
0.04
0.03

Olfr913
0.19
0.22
0.09
0.13
0.15
0.18
0.09
0.07
0.07
0.09

Olfr914
0.18
0.23
0.10
0.14
0.13
0.19
0.10
0.11
0.14
0.11

Olfr915
0.19
0.22
0.14
0.15
0.17
0.19
0.12
0.12
0.13
0.10

Olfr916
0.20
0.28
0.07
0.12
0.07
0.08
0.05
0.04
0.07
0.05

Olfr917
0.17
0.15
0.14
0.18
0.13
0.13
0.13
0.09
0.16
0.14

Olfr918
0.15
0.10
0.08
0.10
0.09
0.10
0.07
0.05
0.09
0.08

Olfr919
0.25
0.27
0.20
0.25
0.20
0.25
0.18
0.19
0.20
0.18

Olfr92
0.47
0.49
0.31
0.36
0.32
0.36
0.27
0.25
0.36
0.29

Olfr920
0.61
0.58
0.39
0.55
0.34
0.36
0.21
0.27
0.28
0.21

Olfr921
0.14
0.13
0.07
0.12
0.08
0.11
0.06
0.05
0.05
0.05

Olfr922
0.24
0.26
0.21
0.19
0.17
0.19
0.14
0.14
0.20
0.16

Olfr923
0.26
0.28
0.20
0.20
0.22
0.24
0.17
0.15
0.17
0.17

Olfr924
0.02
0.06
0.04
0.04
0.03
0.04
NA
NA
0.01
NA

Olfr926
0.05
0.05
0.03
0.04
0.06
0.05
0.01
0.01
0.03
0.02

Olfr93
0.33
0.33
0.21
0.21
0.28
0.30
0.18
0.19
0.28
0.25

Olfr930
0.19
0.21
0.09
0.15
0.12
0.11
0.09
0.08
0.08
0.07

Olfr933
0.24
0.23
0.18
0.21
0.27
0.26
0.15
0.14
0.18
0.17

Olfr934
0.14
0.15
0.07
0.09
0.13
0.12
0.10
0.08
0.08
0.08

Olfr935
0.18
0.23
0.14
0.18
0.17
0.19
0.10
0.09
0.12
0.10

Olfr936
0.08
0.13
0.02
0.05
0.04
0.04
NA
NA
0.03
NA

Olfr937
0.14
0.13
0.07
0.14
0.10
0.12
0.09
0.08
0.07
0.06

Olfr938
0.21
0.22
0.14
0.16
0.13
0.12
0.10
0.09
0.12
0.10

Olfr94
0.22
0.23
0.23
0.24
0.23
0.25
0.24
0.22
0.28
0.30

Olfr943
0.08
0.13
0.07
0.09
0.12
0.10
0.08
0.06
0.08
0.06

Olfr944
0.09
0.10
0.03
0.07
0.07
0.08
0.06
0.05
0.06
0.03

Olfr945
0.07
0.05
0.06
0.07
0.06
0.06
0.04
0.03
0.05
0.04

Olfr947-ps1
0.09
0.08
0.09
0.11
0.12
0.13
0.06
0.06
0.08
0.06

Olfr948
0.04
0.07
0.04
0.02
0.05
0.07
0.02
0.02
NA
NA

Olfr95
0.39
0.37
0.30
0.29
0.34
0.37
0.29
0.28
0.37
0.36

Olfr951
0.12
0.10
0.11
0.10
0.13
0.14
0.10
0.09
0.09
0.09

Olfr952
0.12
0.13
0.05
0.07
0.02
0.05
0.03
0.01
0.04
0.03

Olfr954
0.12
0.10
0.11
0.10
0.13
0.14
0.10
0.09
0.09
0.09

Olfr955
0.18
0.19
0.13
0.11
0.11
0.13
0.11
0.09
0.10
0.09

Olfr957
0.18
0.19
0.12
0.13
0.16
0.18
0.11
0.11
0.10
0.09

Olfr958
0.33
0.36
0.24
0.26
0.27
0.34
0.25
0.23
0.26
0.25

Olfr959
0.34
0.33
0.29
0.29
0.26
0.29
0.23
0.21
0.27
0.25

Olfr96
0.30
0.32
0.25
0.27
0.22
0.22
0.21
0.20
0.24
0.26

Olfr960
0.24
0.24
0.17
0.14
0.15
0.19
0.10
0.07
0.10
0.13

Olfr961
0.13
0.14
0.10
0.14
0.12
0.12
0.08
0.06
0.08
0.07

Olfr963
0.11
0.19
0.14
0.11
0.14
0.15
0.14
0.11
0.10
0.13

Olfr965
0.15
0.19
0.18
0.18
0.15
0.17
0.17
0.15
0.18
0.16

Olfr967
0.16
0.19
0.19
0.20
0.18
0.23
0.18
0.15
0.16
0.15

Olfr968
0.07
0.10
0.04
0.05
0.04
0.03
0.04
0.03
0.02
0.01

Olfr969
0.12
0.12
0.08
0.07
0.10
0.11
0.07
0.06
0.06
0.04

Olfr97
0.12
0.18
0.14
0.15
0.14
0.20
0.07
0.07
0.24
0.19

Olfr970
0.09
0.12
0.04
0.09
0.05
0.09
0.04
0.03
0.03
0.02

Olfr971
0.15
0.16
0.12
0.11
0.13
0.14
0.09
0.09
0.09
0.09

Olfr972
0.12
0.16
0.07
0.08
0.06
0.09
0.04
0.03
0.04
0.04

Olfr974
0.32
0.31
0.27
0.30
0.29
0.33
0.24
0.23
0.30
0.25

Olfr975
0.38
0.43
0.31
0.33
0.33
0.37
0.28
0.27
0.32
0.30

Olfr976
0.23
0.24
0.18
0.20
0.18
0.21
0.16
0.17
0.19
0.17

Olfr978
0.37
0.38
0.25
0.29
0.29
0.30
0.24
0.22
0.28
0.26

Olfr979
0.22
0.24
0.18
0.20
0.16
0.15
0.17
0.16
0.18
0.19

Olfr98
0.12
0.18
0.14
0.15
0.14
0.20
0.07
0.07
0.24
0.19

Olfr980
0.28
0.25
0.22
0.24
0.26
0.27
0.18
0.19
0.20
0.17

Olfr981
0.27
0.26
0.25
0.25
0.21
0.24
0.22
0.21
0.27
0.25

Olfr982
0.46
0.48
0.40
0.44
0.39
0.42
0.34
0.34
0.39
0.38

Olfr983
0.12
0.13
0.06
0.08
0.09
0.12
0.08
0.06
0.05
0.04

Olfr984
0.37
0.40
0.31
0.34
0.36
0.39
0.30
0.28
0.34
0.32

Olfr985
0.26
0.25
0.20
0.18
0.20
0.21
0.19
0.18
0.17
0.19

Olfr986
0.30
0.31
0.24
0.26
0.25
0.24
0.22
0.21
0.22
0.21

Olfr987
0.11
0.13
0.12
0.11
0.10
0.12
0.09
0.07
0.10
0.07

Olfr988
0.24
0.26
0.15
0.22
0.15
0.17
0.13
0.12
0.15
0.08

Olfr99
0.64
0.63
0.42
0.48
0.36
0.42
0.18
0.16
0.36
0.25

Olfr992
0.12
0.11
0.11
0.19
0.10
0.10
0.11
0.09
0.12
0.11

Olfr993
0.17
0.10
0.11
0.11
0.19
0.17
0.03
0.03
0.07
0.04

Olfr994
0.08
0.12
0.08
0.11
0.11
0.07
0.07
0.07
0.08
0.06

Olfr995
0.09
0.08
0.03
0.06
0.07
0.06
0.02
0.02
0.03
0.02

Olfr996
0.03
0.07
0.04
0.06
0.09
0.13
0.05
0.04
0.03
0.04

Olfr998
0.33
0.37
0.19
0.19
0.21
0.22
0.19
0.17
0.19
0.17

Lung
Red

MLN

CD11b −
Pulp
Mo.6C +
DCs
Microglia
Mo.6C −
M0.6C +
M0.6C −

Mφ
Mφ
II − .B1
CD4+
Mφ
II − .B1
II + .B1
II + .B1

Gapdh
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00

Rtp1
0.24
0.30
0.27
0.33
0.31
0.30
0.28
0.33

Rtp2
0.32
0.35
0.31
0.37
0.35
0.38
0.36
0.39

Reep3
0.718
0.693
0.71
0.716
0.601
0.53
0.689
0.576

Cnga1
0.107
0.131
0.115
0.135
0.138
0.107
0.13
0.139

Cnga2
0.153
0.156
0.145
0.199
0.185
0.169
0.15
0.17

Cnga3
0.231
0.263
0.228
0.331
0.303
0.268
0.263
0.3

Cnga4
0.196
0.24
0.209
0.23
0.242
0.264
0.207
0.265

Cngb1
0.257
0.27
0.286
0.253
0.252
0.28
0.244
0.235

Acy3
0.408
0.404
0.313
0.384
0.385
0.389
0.341
0.39

Gna1
0.15
0.17
0.20
0.18
0.19
0.22
0.21
0.22

Olfr1
0.19
0.24
0.21
0.26
0.19
0.28
0.21
0.29

Olfr10
0.20
0.28
0.25
0.26
0.25
0.28
0.22
0.20

Olfr100
0.13
0.15
0.15
0.19
0.20
0.18
0.21
0.19

Olfr1000
0.07
0.08
0.07
0.07
0.10
0.09
0.08
0.14

Olfr1002
0.02
0.04
0.03
0.04
0.02
0.06
0.05
0.10

Olfr1006
0.15
0.20
0.18
0.20
0.22
0.21
0.18
0.23

Olfr1008
0.07
0.11
0.10
0.13
0.10
0.12
0.07
0.15

Olfr1009
0.15
0.15
0.15
0.21
0.21
0.20
0.18
0.21

Olfr101
0.15
0.18
0.18
0.21
0.19
0.20
0.20
0.19

Olfr1010
0.18
0.21
0.19
0.25
0.23
0.25
0.22
0.30

Olfr1012
0.20
0.24
0.23
0.26
0.25
0.24
0.22
0.24

Olfr1013
0.05
0.08
0.07
0.08
0.07
0.09
0.06
0.07

Olfr1014
0.05
0.07
0.06
0.08
0.06
0.09
0.08
0.10

Olfr1015
0.18
0.23
0.22
0.23
0.23
0.25
0.25
0.25

Olfr1016
0.20
0.24
0.23
0.29
0.26
0.25
0.23
0.24

Olfr1018
0.15
0.15
0.15
0.17
0.17
0.19
0.19
0.17

Olfr1019
0.17
0.19
0.19
0.19
0.20
0.21
0.21
0.18

Olfr102
0.13
0.15
0.15
0.19
0.20
0.18
0.21
0.19

Olfr1020
0.05
0.06
0.06
0.09
0.07
0.07
0.05
0.11

Olfr1022
0.06
0.09
0.08
0.11
0.11
0.11
0.09
0.13

Olfr1023
0.10
0.10
0.10
0.14
0.13
0.15
0.13
0.18

Olfr1024
0.15
0.18
0.17
0.16
0.18
0.21
0.20
0.20

Olfr1026
0.09
0.12
0.10
0.14
0.13
0.13
0.14
0.13

Olfr1028
0.08
0.09
0.09
0.10
0.12
0.13
0.10
0.20

Olfr1029
0.12
0.18
0.18
0.18
0.23
0.20
0.24
0.25

Olfr103
0.14
0.14
0.12
0.13
0.14
0.16
0.12
0.15

Olfr1030
0.07
0.11
0.08
0.14
0.13
0.11
0.10
0.10

Olfr1031
0.08
0.08
0.08
0.09
0.09
0.11
0.07
0.12

Olfr1032
0.12
0.14
0.13
0.13
0.15
0.15
0.16
0.19

Olfr1033
0.03
0.03
0.03
0.03
0.04
0.05
0.03
0.08

Olfr1034
0.14
0.20
0.16
0.17
0.16
0.17
0.17
0.16

Olfr1036
0.14
0.20
0.16
0.17
0.16
0.17
0.17
0.16

Olfr1037
0.03
0.04
0.04
0.05
0.05
0.05
0.05
0.10

Olfr1038-ps
0.06
0.10
0.07
0.09
0.09
0.11
0.09
0.11

Olfr1039
NA
NA
0.00
0.02
0.01
0.03
0.01
0.03

Olfr1040
0.16
0.19
0.18
0.18
0.17
0.21
0.19
0.19

Olfr1042
0.20
0.26
0.24
0.27
0.25
0.23
0.25
0.20

Olfr1043
0.15
0.20
0.18
0.19
0.22
0.21
0.18
0.16

Olfr1044
0.10
0.13
0.12
0.12
0.14
0.15
0.15
0.17

Olfr1045
0.10
0.12
0.12
0.12
0.13
0.13
0.15
0.16

Olfr1046
NA
0.02
0.00
0.02
0.02
0.02
0.03
0.04

Olfr1047
NA
NA
NA
NA
−0.01
NA
0.00
0.03

Olfr1048
0.11
0.11
0.11
0.14
0.14
0.13
0.12
0.21

Olfr1049
NA
NA
NA
NA
−0.02
0.01
0.03
0.12

Olfr1051
NA
NA
NA
NA
−0.02
0.01
NA
0.07

Olfr1052
0.07
0.08
0.08
0.09
0.11
0.08
0.12
0.14

Olfr1053
0.13
0.18
0.17
0.22
0.18
0.17
0.17
0.28

Olfr1054
0.15
0.20
0.15
0.20
0.17
0.20
0.17
0.23

Olfr1055
0.07
0.08
0.08
0.08
0.09
0.11
0.09
0.13

Olfr1056
0.13
0.14
0.15
0.15
0.15
0.15
0.13
0.19

Olfr1057
0.12
0.14
0.12
0.15
0.15
0.17
0.16
0.18

Olfr1058
0.05
0.07
0.05
0.06
0.08
0.06
0.08
0.06

Olfr106-ps
0.01
0.03
0.01
0.01
0.02
0.04
0.06
0.06

Olfr1061
NA
NA
NA
0.01
0.01
NA
0.03
0.09

Olfr1062
0.11
0.15
0.11
0.17
0.13
0.11
0.09
0.18

Olfr1065
0.05
0.07
0.05
0.06
0.08
0.06
0.08
0.06

Olfr1066
NA
NA
NA
0.02
0.01
0.00
0.01
0.03

Olfr107
0.04
0.06
0.04
0.07
0.07
0.07
0.06
0.16

Olfr1076
0.06
0.09
0.06
0.04
0.08
0.08
0.08
0.07

Olfr1077-ps1
0.18
0.20
0.19
0.21
0.21
0.21
0.20
0.27

Olfr1079
0.03
0.06
0.06
0.07
0.07
0.08
0.08
0.07

Olfr108
0.03
0.07
0.07
0.08
0.06
0.09
0.09
0.07

Olfr1080
NA
0.01
0.01
0.04
0.03
0.01
0.04
0.08

Olfr1082
NA
NA
NA
NA
0.00
0.01
0.04
0.02

Olfr1084
NA
NA
NA
NA
0.00
NA
NA
0.09

Olfr1085
0.13
0.15
0.16
0.17
0.19
0.23
0.19
0.25

Olfr1086
0.17
0.22
0.20
0.22
0.19
0.24
0.24
0.22

Olfr1087
0.09
0.11
0.10
0.11
0.13
0.11
0.11
0.12

Olfr1089
0.08
0.12
0.09
0.11
0.08
0.12
0.15
0.13

Olfr109
0.23
0.28
0.24
0.28
0.25
0.28
0.28
0.25

Olfr1090
0.06
0.09
0.09
0.10
0.09
0.09
0.07
0.10

Olfr1093
0.17
0.17
0.17
0.19
0.17
0.20
0.20
0.24

Olfr1094
0.06
0.11
0.08
0.10
0.10
0.08
0.07
0.17

Olfr1095
0.00
0.03
0.04
0.06
0.05
0.09
0.04
0.08

Olfr1097
0.04
0.08
0.06
0.07
0.07
0.09
0.10
0.06

Olfr1098
0.06
0.07
0.06
0.06
0.07
0.07
0.07
0.12

Olfr1099
0.12
0.18
0.18
0.16
0.19
0.18
0.17
0.14

Olfr11
0.21
0.25
0.24
0.28
0.24
0.27
0.24
0.32

Olfr110
0.15
0.19
0.16
0.21
0.25
0.19
0.18
0.18

Olfr1100
0.02
0.04
0.03
0.04
0.04
0.05
0.05
0.06

Olfr1101
0.08
0.11
0.10
0.11
0.11
0.17
0.14
0.17

Olfr1102
0.00
0.01
0.02
0.02
0.02
0.03
0.04
0.01

Olfr1104
0.13
0.15
0.12
0.17
0.15
0.17
0.18
0.13

Olfr1105
0.18
0.21
0.20
0.23
0.21
0.25
0.24
0.18

Olfr1106
0.07
0.10
0.08
0.10
0.10
0.11
0.11
0.12

Olfr1107
0.02
0.04
0.02
0.04
0.06
0.03
0.03
0.06

Olfr1109
0.01
0.05
0.04
0.07
0.06
0.06
0.07
0.19

Olfr111
0.18
0.21
0.10
0.36
0.37
0.14
0.15
0.16

Olfr1110
0.07
0.12
0.12
0.15
0.09
0.13
0.16
0.16

Olfr1111
0.11
0.12
0.11
0.13
0.13
0.12
0.13
0.14

Olfr1112
0.03
0.05
0.04
0.07
0.08
0.06
0.08
0.05

Olfr1113
0.07
0.14
0.11
0.14
0.14
0.11
0.13
0.12

Olfr1115
0.16
0.20
0.18
0.20
0.19
0.22
0.20
0.22

Olfr1116
0.01
0.02
0.02
0.03
0.02
0.02
0.03
0.08

Olfr1118
0.11
0.16
0.14
0.14
0.15
0.16
0.15
0.20

Olfr112
0.02
0.05
0.04
0.03
0.05
0.04
0.05
0.08

Olfr1120
0.10
0.14
0.12
0.16
0.15
0.16
0.16
0.20

Olfr1121
0.08
0.13
0.09
0.11
0.12
0.10
0.09
0.15

Olfr1122
0.16
0.19
0.15
0.18
0.18
0.18
0.18
0.20

Olfr1123
0.05
0.07
0.05
0.08
0.08
0.07
0.07
0.06

Olfr1124
NA
0.03
0.01
0.01
0.02
0.03
0.04
0.04

Olfr1126
0.16
0.20
0.18
0.21
0.20
0.22
0.19
0.20

Olfr1128
0.17
0.23
0.20
0.25
0.25
0.23
0.21
0.27

Olfr1129
0.05
0.08
0.06
0.10
0.09
0.09
0.08
0.14

Olfr113
0.21
0.25
0.24
0.20
0.25
0.28
0.24
0.26

Olfr1130
0.05
0.10
0.06
0.10
0.08
0.10
0.10
0.14

Olfr1131
0.07
0.11
0.10
0.11
0.11
0.10
0.14
0.21

Olfr1132
0.15
0.14
0.15
0.18
0.17
0.18
0.16
0.25

Olfr1133
0.17
0.20
0.19
0.20
0.20
0.22
0.20
0.25

Olfr1134
0.03
0.04
0.02
0.05
0.04
0.09
0.06
0.15

Olfr1135
0.03
0.06
0.06
0.06
0.06
0.05
0.07
0.07

Olfr1136
0.11
0.13
0.12
0.14
0.14
0.15
0.15
0.16

Olfr1137
0.13
0.14
0.15
0.15
0.19
0.17
0.18
0.23

Olfr1138
0.11
0.14
0.13
0.15
0.15
0.15
0.13
0.16

Olfr114
0.10
0.14
0.10
0.14
0.13
0.16
0.13
0.23

Olfr1140
0.10
0.11
0.09
0.13
0.12
0.14
0.13
0.13

Olfr1141
0.05
0.09
0.06
0.08
0.08
0.07
0.08
0.09

Olfr1143
0.06
0.08
0.08
0.08
0.07
0.09
0.09
0.07

Olfr1145
0.10
0.13
0.10
0.11
0.11
0.13
0.14
0.14

Olfr1148
0.35
0.35
0.32
0.33
0.34
0.32
0.29
0.23

Olfr115
0.18
0.21
0.19
0.21
0.20
0.20
0.20
0.18

Olfr1151
0.09
0.15
0.12
0.13
0.13
0.11
0.14
0.16

Olfr1152
0.31
0.38
0.37
0.35
0.35
0.39
0.31
0.35

Olfr1153
0.13
0.15
0.14
0.18
0.18
0.17
0.19
0.17

Olfr1154
0.07
0.10
0.08
0.11
0.11
0.11
0.13
0.22

Olfr1155
0.25
0.29
0.27
0.29
0.29
0.31
0.30
0.33

Olfr1156
0.17
0.20
0.21
0.23
0.22
0.23
0.22
0.20

Olfr1157
0.14
0.16
0.12
0.16
0.16
0.17
0.15
0.17

Olfr1158
0.09
0.11
0.08
0.12
0.12
0.13
0.11
0.11

Olfr116
0.07
0.09
0.08
0.13
0.14
0.10
0.09
0.16

Olfr1160
NA
0.00
0.01
0.03
0.00
NA
0.09
0.08

Olfr1161
0.09
0.11
0.08
0.11
0.11
0.10
0.10
0.16

Olfr1162
0.20
0.23
0.21
0.25
0.22
0.25
0.26
0.25

Olfr1163
0.20
0.23
0.21
0.25
0.22
0.25
0.26
0.25

Olfr1164
0.09
0.07
0.09
0.10
0.07
0.13
0.09
0.15

Olfr1166
0.07
0.11
0.08
0.15
0.10
0.12
0.10
0.15

Olfr1167
0.02
0.01
0.03
0.03
0.03
0.04
0.04
0.04

Olfr1168
0.09
0.12
0.11
0.13
0.13
0.14
0.13
0.20

Olfr117
0.09
0.13
0.11
0.10
0.13
0.12
0.14
0.18

Olfr1170
0.08
0.12
0.09
0.11
0.12
0.10
0.08
0.11

Olfr1173
0.05
0.08
0.06
0.06
0.06
0.08
0.09
0.11

Olfr1174-ps
0.57
0.69
0.61
0.72
0.78
0.67
0.61
0.59

Olfr1176
0.05
0.07
0.07
0.09
0.08
0.08
0.09
0.13

Olfr1178
0.06
0.07
0.06
0.08
0.09
0.08
0.07
0.09

Olfr1179
0.15
0.17
0.17
0.16
0.21
0.21
0.23
0.21

Olfr118
0.12
0.12
0.10
0.16
0.14
0.10
0.16
0.30

Olfr1180
0.06
0.08
0.07
0.09
0.08
0.08
0.08
0.14

Olfr1181
0.03
0.04
0.02
0.04
0.04
0.09
0.08
0.10

Olfr1182
0.09
0.09
0.10
0.13
0.09
0.14
0.15
0.19

Olfr1183
0.01
0.03
NA
0.03
0.10
0.03
0.03
0.08

Olfr1184
0.04
0.05
0.06
0.08
0.08
0.08
0.07
0.05

Olfr1186
0.01
0.04
0.02
0.05
0.05
0.06
0.05
0.06

Olfr1188
0.12
0.13
0.11
0.18
0.16
0.14
0.16
0.15

Olfr1189
0.06
0.07
0.07
0.09
0.10
0.10
0.07
0.10

Olfr119
0.08
0.12
0.10
0.11
0.14
0.12
0.12
0.18

Olfr1193
0.08
0.10
0.11
0.08
0.10
0.12
0.05
0.11

Olfr1195
0.03
0.04
0.04
0.08
0.07
0.08
0.07
0.04

Olfr1196
0.14
0.18
0.14
0.18
0.21
0.18
0.17
0.20

Olfr1197
0.14
0.18
0.14
0.18
0.21
0.18
0.17
0.20

Olfr1198
0.04
0.05
0.04
0.04
0.04
0.04
0.07
0.11

Olfr1199
0.01
NA
0.02
0.03
0.01
0.02
0.02
0.08

Olfr12
0.24
0.27
0.25
0.31
0.27
0.29
0.27
0.25

Olfr120
0.08
0.16
0.11
0.13
0.14
0.14
0.14
0.11

Olfr1200
0.20
0.23
0.20
0.26
0.24
0.26
0.22
0.20

Olfr1201
0.12
0.13
0.13
0.15
0.16
0.12
0.15
0.19

Olfr1202
0.05
0.08
0.05
0.08
0.09
0.09
0.07
0.11

Olfr1204
0.07
0.06
0.06
0.09
0.06
0.06
0.09
0.15

Olfr1205
0.12
0.13
0.13
0.15
0.16
0.12
0.15
0.19

Olfr1206
0.12
0.13
0.13
0.15
0.16
0.12
0.15
0.19

Olfr1208
0.06
0.09
0.10
0.08
0.08
0.11
0.08
0.14

Olfr1209
0.14
0.17
0.15
0.18
0.16
0.20
0.19
0.18

Olfr121
0.09
0.14
0.11
0.14
0.13
0.12
0.10
0.20

Olfr1211
0.08
0.09
0.08
0.10
0.09
0.11
0.10
0.11

Olfr1212
0.00
0.02
0.02
0.03
0.04
0.04
0.05
0.05

Olfr1213
0.06
0.09
0.07
0.09
0.10
0.07
0.08
0.10

Olfr1214
0.04
0.06
0.04
0.03
0.05
0.04
0.05
0.12

Olfr1215
0.05
0.10
0.07
0.08
0.09
0.12
0.10
0.15

Olfr1216
0.05
0.06
0.04
0.05
0.03
0.04
0.10
0.09

Olfr1217
0.00
0.03
0.01
0.04
0.04
0.02
0.03
0.06

Olfr1218
0.05
0.07
0.05
0.08
0.08
0.07
0.08
0.12

Olfr1219
0.07
0.09
0.09
0.12
0.13
0.10
0.11
0.12

Olfr122
0.19
0.24
0.22
0.26
0.30
0.29
0.24
0.29

Olfr1220
0.06
0.06
0.05
0.07
0.08
0.09
0.09
0.09

Olfr1221
NA
0.02
NA
0.00
0.00
0.00
0.02
0.04

Olfr1222
0.19
0.23
0.22
0.22
0.30
0.25
0.27
0.22

Olfr1223
0.07
0.10
0.08
0.07
0.09
0.11
0.07
0.13

Olfr1225
0.10
0.15
0.13
0.15
0.12
0.16
0.15
0.20

Olfr1226
0.13
0.19
0.15
0.18
0.18
0.16
0.19
0.20

Olfr1228
0.01
0.04
0.04
0.05
0.05
0.04
0.05
0.06

Olfr1229
0.30
0.33
0.30
0.38
0.37
0.35
0.32
0.38

Olfr123
0.18
0.25
0.23
0.23
0.23
0.30
0.24
0.25

Olfr1230
0.15
0.20
0.19
0.18
0.17
0.22
0.16
0.19

Olfr1231
0.11
0.16
0.13
0.15
0.17
0.16
0.14
0.17

Olfr1232
0.03
0.04
0.02
0.03
0.03
0.04
0.08
0.11

Olfr1233
0.13
0.16
0.14
0.17
0.14
0.19
0.14
0.14

Olfr1234
0.09
0.10
0.10
0.11
0.12
0.14
0.10
0.15

Olfr1238
0.13
0.14
0.14
0.15
0.19
0.16
0.13
0.18

Olfr1239
0.15
0.21
0.17
0.19
0.21
0.24
0.19
0.21

Olfr124
0.13
0.17
0.17
0.19
0.19
0.17
0.18
0.21

Olfr1240
0.09
0.09
0.09
0.13
0.10
0.12
0.12
0.16

Olfr1241
0.08
0.12
0.08
0.11
0.11
0.12
0.10
0.14

Olfr1242
0.11
0.13
0.14
0.13
0.13
0.16
0.15
0.17

Olfr1243
0.06
0.07
0.07
0.09
0.06
0.07
0.07
0.09

Olfr1245
0.01
0.05
0.06
0.07
0.06
0.09
0.06
0.16

Olfr1246
NA
0.02
0.01
0.02
0.02
0.02
0.01
0.04

Olfr1247
0.05
0.07
0.06
0.09
0.07
0.07
0.08
0.13

Olfr1248
NA
NA
0.01
NA
−0.02
0.00
NA
0.02

Olfr1249
0.09
0.13
0.12
0.16
0.16
0.13
0.15
0.18

Olfr125
0.03
0.05
0.05
0.04
0.05
0.05
0.04
0.08

Olfr1250
0.01
0.05
0.03
0.02
0.04
0.04
0.04
0.07

Olfr1251
NA
NA
NA
NA
−0.02
0.02
NA
0.02

Olfr1252
0.10
0.14
0.11
0.12
0.15
0.15
0.14
0.14

Olfr1253
0.02
0.05
NA
NA
0.04
0.03
0.05
0.09

Olfr1254
NA
NA
NA
0.01
0.00
0.01
0.00
0.06

Olfr1255
0.11
0.14
0.14
0.14
0.15
0.15
0.16
0.19

Olfr1256
0.13
0.17
0.15
0.18
0.17
0.17
0.18
0.17

Olfr1257
0.04
0.04
0.04
0.05
0.09
0.06
0.07
0.09

Olfr1258
0.14
0.16
0.15
0.19
0.17
0.18
0.17
0.19

Olfr1259
0.13
0.15
0.15
0.20
0.15
0.17
0.15
0.16

Olfr126
0.09
0.09
0.08
0.10
0.11
0.09
0.11
0.13

Olfr1260
0.18
0.23
0.21
0.21
0.22
0.25
0.25
0.21

Olfr1261
0.02
0.03
0.02
0.05
0.04
0.05
0.07
0.11

Olfr1262
0.16
0.20
0.17
0.22
0.22
0.21
0.22
0.27

Olfr1263
0.11
0.15
0.12
0.18
0.15
0.14
0.17
0.12

Olfr1264
0.13
0.16
0.13
0.19
0.17
0.17
0.17
0.16

Olfr1265
0.08
0.11
0.07
0.13
0.14
0.10
0.13
0.10

Olfr1269
0.08
0.11
0.07
0.13
0.14
0.10
0.13
0.10

Olfr127
0.09
0.09
0.08
0.10
0.11
0.09
0.11
0.13

Olfr1270
0.08
0.10
0.08
0.12
0.12
0.12
0.13
0.16

Olfr1271
0.09
0.12
0.09
0.10
0.09
0.12
0.12
0.17

Olfr1272
0.24
0.29
0.24
0.30
0.30
0.28
0.26
0.30

Olfr1273-ps
NA
0.01
0.01
0.01
0.03
0.01
0.02
0.08

Olfr1274-ps
0.14
0.18
0.20
0.19
0.15
0.14
0.19
0.19

Olfr1275
0.08
0.10
0.08
0.09
0.13
0.12
0.10
0.11

Olfr1276
0.16
0.18
0.15
0.19
0.18
0.20
0.20
0.21

Olfr1277
0.20
0.22
0.20
0.25
0.23
0.29
0.20
0.21

Olfr1278
0.10
0.11
0.09
0.12
0.11
0.12
0.12
0.11

Olfr1279
0.22
0.27
0.23
0.27
0.26
0.27
0.28
0.28

Olfr128
0.09
0.09
0.08
0.10
0.11
0.09
0.11
0.13

Olfr1280
0.07
0.07
0.06
0.07
0.07
0.08
0.07
0.10

Olfr1281
0.03
0.02
0.03
0.05
0.03
0.06
0.04
0.10

Olfr1282
0.07
0.07
0.06
0.07
0.07
0.08
0.07
0.10

Olfr1283
0.07
0.07
0.06
0.07
0.07
0.08
0.07
0.10

Olfr1284
0.23
0.28
0.27
0.28
0.26
0.27
0.28
0.28

Olfr1286
0.07
0.07
0.06
0.07
0.07
0.08
0.07
0.10

Olfr1287
0.07
0.07
0.06
0.07
0.07
0.08
0.07
0.10

Olfr1288
0.04
0.05
0.05
0.07
0.06
0.04
0.04
0.14

Olfr1289
0.04
0.07
0.05
0.07
0.06
0.06
0.07
0.11

Olfr129
0.21
0.27
0.26
0.26
0.27
0.25
0.27
0.28

Olfr1290
0.05
0.10
0.06
0.09
0.11
0.06
0.11
0.12

Olfr1294
0.09
0.12
0.09
0.11
0.11
0.12
0.11
0.11

Olfr1295
0.07
0.10
0.10
0.11
0.11
0.13
0.11
0.09

Olfr1297
0.04
0.07
0.05
0.07
0.08
0.07
0.07
0.09

Olfr1298
0.05
0.06
0.07
0.06
0.07
0.10
0.11
0.06

Olfr1299
0.06
0.11
0.06
0.11
0.09
0.11
0.10
0.14

Olfr13
0.24
0.31
0.25
0.32
0.29
0.28
0.30
0.27

Olfr130
0.09
0.11
0.11
0.11
0.13
0.10
0.11
0.15

Olfr1300-ps1
0.04
0.04
0.05
0.07
0.07
0.04
0.06
0.08

Olfr1301
0.13
0.16
0.15
0.18
0.15
0.18
0.17
0.16

Olfr1302
0.02
0.02
0.03
0.04
0.02
0.02
0.02
0.05

Olfr1303
0.07
0.10
0.07
0.09
0.11
0.12
0.08
0.13

Olfr1305
0.09
0.11
0.09
0.11
0.13
0.12
0.14
0.14

Olfr1306
NA
NA
NA
0.00
0.02
0.01
0.01
0.05

Olfr1307
0.08
0.15
0.10
0.11
0.12
0.16
0.11
0.17

Olfr1308
NA
0.00
0.00
0.03
0.01
0.01
0.03
0.05

Olfr1309
0.14
0.17
0.17
0.16
0.17
0.17
0.17
0.14

Olfr131
0.12
0.14
0.12
0.16
0.14
0.15
0.13
0.15

Olfr1310
0.09
0.12
0.10
0.16
0.13
0.13
0.13
0.16

Olfr1311
0.12
0.15
0.12
0.18
0.13
0.16
0.17
0.14

Olfr1312
0.01
0.06
0.03
0.01
0.04
0.06
0.02
0.06

Olfr1313
0.09
0.12
0.10
0.12
0.13
0.11
0.15
0.14

Olfr1314
0.09
0.10
0.09
0.11
0.10
0.09
0.11
0.11

Olfr1316
0.07
0.09
0.09
0.10
0.12
0.11
0.12
0.12

Olfr1317
0.03
0.05
0.05
0.08
0.06
0.05
0.06
0.14

Olfr1318
0.06
0.11
0.09
0.11
0.11
0.10
0.08
0.11

Olfr132
0.12
0.14
0.13
0.17
0.15
0.20
0.15
0.18

Olfr1320
0.15
0.20
0.17
0.20
0.19
0.21
0.19
0.20

Olfr1321
0.11
0.12
0.13
0.14
0.15
0.17
0.11
0.17

Olfr1322
0.20
0.21
0.21
0.22
0.22
0.25
0.25
0.21

Olfr1323
0.10
0.14
0.11
0.12
0.12
0.15
0.12
0.13

Olfr1324
0.18
0.24
0.20
0.21
0.23
0.22
0.23
0.24

Olfr1325
0.07
0.09
0.08
0.12
0.09
0.11
0.09
0.13

Olfr1328
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1329
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr133
0.01
0.04
0.04
0.06
0.04
0.06
0.05
0.05

Olfr1330
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1331
0.13
0.20
0.16
0.21
0.23
0.21
0.22
0.22

Olfr1333
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1335
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1336
0.23
0.28
0.24
0.28
0.26
0.29
0.23
0.26

Olfr1337
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1338
0.17
0.21
0.21
0.26
0.23
0.23
0.24
0.22

Olfr1339
0.30
0.34
0.32
0.36
0.34
0.36
0.36
0.30

Olfr134
NA
NA
NA
0.03
0.01
0.00
0.01
0.04

Olfr1340
0.26
0.30
0.26
0.36
0.33
0.29
0.29
0.36

Olfr1341
0.12
0.16
0.14
0.15
0.18
0.18
0.17
0.19

Olfr1342
0.23
0.25
0.26
0.32
0.26
0.30
0.29
0.24

Olfr1344
0.28
0.32
0.28
0.32
0.32
0.35
0.31
0.32

Olfr1346
0.32
0.37
0.32
0.42
0.41
0.38
0.36
0.45

Olfr1347
0.37
0.46
0.38
0.46
0.48
0.48
0.40
0.47

Olfr1348
0.26
0.26
0.24
0.29
0.28
0.32
0.29
0.27

Olfr1349
0.36
0.41
0.37
0.44
0.43
0.42
0.41
0.41

Olfr135
0.02
0.04
0.01
0.06
0.05
0.04
0.06
0.07

Olfr1350
0.24
0.27
0.24
0.30
0.28
0.29
0.26
0.28

Olfr1351
0.13
0.15
0.17
0.18
0.15
0.16
0.18
0.17

Olfr1352
0.10
0.12
0.10
0.15
0.12
0.11
0.14
0.16

Olfr1353
0.09
0.11
0.10
0.12
0.11
0.13
0.12
0.14

Olfr1354
0.16
0.19
0.18
0.21
0.21
0.21
0.19
0.24

Olfr1355
0.16
0.19
0.18
0.21
0.21
0.21
0.19
0.24

Olfr1356
0.08
0.10
0.09
0.11
0.11
0.12
0.09
0.14

Olfr1357
0.20
0.23
0.20
0.22
0.23
0.24
0.20
0.29

Olfr1359
0.22
0.29
0.25
0.28
0.29
0.28
0.28
0.28

Olfr136
0.03
0.04
0.04
0.04
0.07
0.06
0.07
0.09

Olfr1360
0.22
0.29
0.25
0.28
0.29
0.28
0.28
0.28

Olfr1361
0.25
0.27
0.25
0.30
0.27
0.28
0.23
0.29

Olfr1362
0.31
0.35
0.33
0.34
0.36
0.35
0.30
0.33

Olfr1364
0.29
0.31
0.30
0.33
0.32
0.30
0.33
0.31

Olfr1366
0.24
0.27
0.28
0.27
0.26
0.30
0.32
0.27

Olfr1367
0.11
0.11
0.11
0.15
0.13
0.10
0.12
0.22

Olfr1368
0.08
0.09
0.08
0.10
0.08
0.11
0.14
0.15

Olfr137
0.22
0.24
0.22
0.25
0.25
0.25
0.21
0.25

Olfr1370
0.16
0.19
0.19
0.20
0.18
0.18
0.21
0.23

Olfr1371
0.24
0.22
0.18
0.28
0.25
0.22
0.20
0.20

Olfr1372-ps1
0.13
0.12
0.10
0.14
0.16
0.12
0.14
0.18

Olfr1373
0.24
0.22
0.18
0.28
0.25
0.22
0.20
0.20

Olfr1377
0.17
0.25
0.21
0.26
0.20
0.22
0.21
0.26

Olfr1378
0.24
0.26
0.26
0.27
0.27
0.26
0.27
0.31

Olfr138
NA
NA
NA
NA
0.01
0.01
0.02
NA

Olfr1380
0.24
0.22
0.18
0.28
0.25
0.22
0.20
0.20

Olfr1381
0.24
0.22
0.18
0.28
0.25
0.22
0.20
0.20

Olfr1382
0.24
0.22
0.18
0.28
0.25
0.22
0.20
0.20

Olfr1383
0.20
0.26
0.20
0.27
0.29
0.24
0.21
0.33

Olfr1384
0.16
0.22
0.18
0.23
0.22
0.23
0.21
0.19

Olfr1385
0.18
0.22
0.19
0.22
0.20
0.20
0.22
0.23

Olfr1386
0.18
0.22
0.19
0.22
0.20
0.20
0.22
0.23

Olfr1387
0.15
0.19
0.15
0.20
0.17
0.20
0.14
0.17

Olfr1388
0.25
0.32
0.28
0.32
0.31
0.30
0.29
0.35

Olfr1389
0.21
0.26
0.26
0.25
0.25
0.30
0.27
0.27

Olfr139
0.28
0.34
0.28
0.35
0.35
0.35
0.34
0.35

Olfr1390
0.25
0.25
0.27
0.28
0.29
0.28
0.30
0.25

Olfr1391
0.18
0.21
0.17
0.21
0.21
0.24
0.22
0.21

Olfr1392
0.23
0.28
0.25
0.29
0.29
0.28
0.27
0.36

Olfr1393
0.29
0.38
0.34
0.39
0.33
0.37
0.36
0.35

Olfr1394
0.38
0.43
0.41
0.46
0.46
0.45
0.43
0.46

Olfr1395
0.41
0.46
0.42
0.49
0.47
0.46
0.46
0.44

Olfr1396
0.20
0.24
0.25
0.30
0.25
0.28
0.29
0.19

Olfr140
0.21
0.30
0.27
0.30
0.27
0.31
0.26
0.27

Olfr1402
0.26
0.32
0.30
0.32
0.31
0.33
0.29
0.35

Olfr1404
0.08
0.11
0.09
0.14
0.12
0.10
0.12
0.11

Olfr1406
0.09
0.13
0.13
0.13
0.13
0.14
0.09
0.14

Olfr1408
0.14
0.16
0.17
0.17
0.18
0.21
0.20
0.21

Olfr141
0.09
0.10
0.11
0.12
0.10
0.11
0.12
0.13

Olfr1410
0.37
0.45
0.40
0.42
0.40
0.46
0.41
0.42

Olfr1411
0.21
0.28
0.24
0.30
0.25
0.27
0.25
0.29

Olfr1412
0.30
0.32
0.29
0.33
0.29
0.35
0.30
0.25

Olfr1413
0.30
0.35
0.34
0.37
0.34
0.37
0.36
0.31

Olfr1414
0.32
0.37
0.36
0.39
0.39
0.40
0.37
0.35

Olfr1415
0.32
0.37
0.36
0.39
0.39
0.40
0.37
0.35

Olfr1416
0.32
0.37
0.36
0.39
0.39
0.40
0.37
0.35

Olfr1417
0.23
0.29
0.27
0.29
0.32
0.33
0.30
0.29

Olfr1418
0.18
0.23
0.23
0.19
0.24
0.18
0.22
0.23

Olfr1419
0.22
0.22
0.24
0.26
0.25
0.26
0.21
0.23

Olfr142
0.06
0.11
0.10
0.13
0.12
0.13
0.11
0.15

Olfr1420
0.20
0.23
0.21
0.22
0.21
0.22
0.23
0.26

Olfr1423
0.17
0.22
0.19
0.23
0.23
0.22
0.22
0.22

Olfr1424
0.04
0.09
0.05
0.05
0.08
0.09
0.09
0.10

Olfr1425
0.19
0.25
0.22
0.27
0.22
0.25
0.24
0.25

Olfr1426
0.19
0.24
0.20
0.22
0.21
0.22
0.19
0.28

Olfr1427
0.17
0.19
0.16
0.19
0.19
0.21
0.17
0.24

Olfr1428
0.25
0.30
0.25
0.31
0.28
0.28
0.26
0.27

Olfr143
0.16
0.21
0.19
0.19
0.19
0.21
0.20
0.23

Olfr1431
0.07
0.10
0.10
0.10
0.10
0.11
0.08
0.12

Olfr1434
NA
NA
0.02
0.03
0.04
0.03
0.06
0.12

Olfr1436
0.00
0.05
NA
0.01
0.03
0.03
0.05
0.03

Olfr1437
0.09
0.15
0.14
0.14
0.11
0.13
0.17
0.17

Olfr1440
0.20
0.24
0.21
0.22
0.21
0.24
0.22
0.27

Olfr1441
0.16
0.18
0.15
0.17
0.18
0.21
0.18
0.17

Olfr1442
0.10
0.11
0.11
0.11
0.12
0.14
0.12
0.13

Olfr1443
0.02
0.04
0.04
0.06
0.05
0.07
0.05
0.06

Olfr1444
0.12
0.14
0.15
0.18
0.15
0.16
0.15
0.16

Olfr1445
0.10
0.15
0.14
0.16
0.15
0.16
0.14
0.13

Olfr1446
0.05
0.07
0.07
0.06
0.10
0.08
0.06
0.10

Olfr1447
0.06
0.07
0.07
0.09
0.09
0.09
0.11
0.12

Olfr1448
0.02
0.04
0.03
0.05
0.07
0.05
0.07
0.08

Olfr1449
0.19
0.20
0.21
0.20
0.21
0.22
0.24
0.27

Olfr145
0.16
0.20
0.18
0.23
0.21
0.22
0.20
0.19

Olfr1450
0.14
0.16
0.17
0.16
0.17
0.18
0.17
0.18

Olfr1451
0.05
0.08
0.06
0.08
0.07
0.07
0.06
0.08

Olfr1453
0.08
0.13
0.10
0.13
0.13
0.12
0.13
0.20

Olfr1454
0.03
0.06
0.04
0.07
0.05
0.04
0.05
0.06

Olfr1457
0.01
0.03
0.02
0.03
0.03
0.01
0.02
0.05

Olfr1459
0.05
0.06
0.08
0.07
0.07
0.08
0.05
0.10

Olfr146
0.07
0.10
0.07
0.10
0.08
0.10
0.09
0.12

Olfr1461
0.12
0.15
0.13
0.18
0.12
0.17
0.17
0.15

Olfr1462
0.03
0.05
0.04
0.04
0.08
0.04
0.08
0.08

Olfr1463
0.22
0.21
0.23
0.25
0.24
0.22
0.23
0.22

Olfr1465
0.19
0.21
0.21
0.24
0.21
0.22
0.19
0.29

Olfr1466
0.07
0.11
0.09
0.13
0.09
0.13
0.15
0.11

Olfr1467
0.07
0.10
0.08
0.10
0.11
0.10
0.10
0.17

Olfr1469
0.06
0.10
0.08
0.10
0.10
0.11
0.10
0.10

Olfr147
0.27
0.33
0.30
0.34
0.31
0.34
0.31
0.36

Olfr1471
0.03
0.04
0.04
0.03
0.05
0.07
0.04
0.10

Olfr1472
0.06
0.07
0.09
0.08
0.09
0.09
0.09
0.11

Olfr1474
0.08
0.10
0.08
0.13
0.12
0.10
0.11
0.16

Olfr1475
0.01
0.04
0.04
0.06
0.07
0.06
0.04
0.14

Olfr1477
NA
NA
NA
NA
−0.01
0.01
NA
0.05

Olfr148
0.15
0.21
0.18
0.20
0.23
0.21
0.19
0.24

Olfr1480
0.07
0.10
0.10
0.11
0.10
0.09
0.10
0.12

Olfr1484
0.07
0.09
0.07
0.10
0.08
0.10
0.07
0.08

Olfr1487
0.02
0.05
0.04
0.05
0.07
0.10
0.04
0.09

Olfr1489
0.06
0.09
0.06
0.09
0.09
0.09
0.10
0.11

Olfr149
0.33
0.41
0.36
0.38
0.39
0.42
0.38
0.40

Olfr1490
0.18
0.23
0.20
0.23
0.20
0.24
0.20
0.22

Olfr1491
0.22
0.26
0.25
0.31
0.30
0.31
0.26
0.21

Olfr1494
0.08
0.08
0.07
0.08
0.09
0.08
0.10
0.11

Olfr1495
0.20
0.26
0.21
0.28
0.28
0.27
0.25
0.33

Olfr1496
0.03
0.03
0.03
0.05
0.05
0.04
0.05
0.05

Olfr1497
0.31
0.33
0.31
0.38
0.34
0.36
0.33
0.39

Olfr1499
0.10
0.11
0.11
0.15
0.11
0.12
0.14
0.16

Olfr15
0.13
0.17
0.13
0.20
0.17
0.19
0.18
0.23

Olfr150
0.15
0.23
0.20
0.21
0.20
0.25
0.22
0.24

Olfr1500
0.19
0.25
0.21
0.24
0.23
0.25
0.22
0.30

Olfr1501
0.04
0.08
0.06
0.08
0.08
0.10
0.08
0.16

Olfr1502
0.22
0.27
0.24
0.26
0.26
0.26
0.27
0.28

Olfr1504
0.09
0.13
0.09
0.13
0.12
0.13
0.11
0.18

Olfr1505
0.16
0.19
0.16
0.20
0.22
0.24
0.19
0.18

Olfr1506
0.17
0.23
0.23
0.27
0.23
0.25
0.21
0.23

Olfr1507
0.07
0.10
0.08
0.09
0.13
0.11
0.13
0.13

Olfr1508
0.18
0.22
0.18
0.22
0.22
0.27
0.21
0.18

Olfr1509
0.09
0.11
0.10
0.14
0.10
0.15
0.11
0.16

Olfr151
0.09
0.13
0.10
0.13
0.12
0.14
0.13
0.13

Olfr1510
0.31
0.42
0.34
0.44
0.41
0.40
0.36
0.40

Olfr1511
0.19
0.28
0.24
0.26
0.28
0.25
0.24
0.29

Olfr1512
0.12
0.16
0.13
0.17
0.16
0.16
0.16
0.21

Olfr1513
0.12
0.16
0.13
0.17
0.16
0.16
0.16
0.21

Olfr152
0.12
0.15
0.14
0.14
0.21
0.16
0.17
0.23

Olfr153
0.07
0.10
0.09
0.12
0.13
0.10
0.09
0.15

Olfr1532-ps1
0.31
0.39
0.35
0.40
0.38
0.41
0.38
0.39

Olfr1535
0.22
0.29
0.26
0.26
0.25
0.26
0.26
0.24

Olfr1537
0.08
0.16
0.10
0.10
0.10
0.08
0.14
0.08

Olfr154
0.08
0.11
0.08
0.10
0.10
0.11
0.10
0.15

Olfr155
0.24
0.25
0.24
0.28
0.27
0.26
0.27
0.30

Olfr156
0.12
0.16
0.12
0.18
0.17
0.19
0.13
0.17

Olfr157
0.28
0.35
0.32
0.33
0.35
0.36
0.34
0.37

Olfr159
0.20
0.21
0.20
0.24
0.20
0.23
0.22
0.24

Olfr16
0.21
0.24
0.23
0.24
0.22
0.26
0.23
0.26

Olfr160
0.18
0.22
0.19
0.22
0.18
0.22
0.21
0.22

Olfr161
0.22
0.27
0.25
0.27
0.26
0.28
0.28
0.26

Olfr164
0.09
0.13
0.13
0.18
0.16
0.14
0.16
0.15

Olfr165
0.13
0.17
0.16
0.19
0.21
0.20
0.17
0.23

Olfr166
0.20
0.21
0.15
0.23
0.18
0.15
0.17
0.23

Olfr167
0.09
0.13
0.12
0.13
0.15
0.13
0.11
0.10

Olfr168
0.09
0.14
0.12
0.15
0.15
0.12
0.14
0.18

Olfr169
0.26
0.32
0.25
0.33
0.34
0.30
0.32
0.33

Olfr17
0.16
0.21
0.18
0.20
0.21
0.24
0.22
0.27

Olfr170
0.26
0.32
0.25
0.33
0.34
0.30
0.32
0.33

Olfr171
0.26
0.32
0.25
0.33
0.34
0.30
0.32
0.33

Olfr172
0.11
0.18
0.19
0.15
0.15
0.17
0.23
0.19

Olfr173
0.04
0.07
0.09
0.07
0.05
0.08
0.10
0.13

Olfr175-ps1
NA
NA
0.00
0.01
0.01
0.01
0.02
0.05

Olfr176
0.02
0.03
0.03
0.03
0.05
0.05
0.06
0.07

Olfr177
0.02
0.03
0.03
0.03
0.05
0.05
0.06
0.07

Olfr178
NA
0.02
0.01
0.04
−0.01
0.03
0.00
0.09

Olfr18
0.06
0.08
0.06
0.10
0.09
0.10
0.07
0.14

Olfr180
0.18
0.21
0.19
0.21
0.18
0.27
0.22
0.20

Olfr181
0.00
0.01
0.01
0.04
0.00
0.01
0.02
0.06

Olfr183
0.04
0.06
0.04
0.05
0.07
0.05
0.08
0.08

Olfr186
0.04
0.06
0.06
0.09
0.09
0.08
0.10
0.13

Olfr187
0.06
0.04
0.06
0.08
0.07
0.08
0.10
0.07

Olfr19
0.19
0.24
0.21
0.23
0.22
0.21
0.22
0.19

Olfr190
NA
0.01
NA
0.01
0.01
NA
0.03
0.09

Olfr191
0.02
0.04
0.03
0.04
0.03
0.02
0.05
0.06

Olfr192
NA
NA
NA
0.01
0.01
NA
0.02
0.01

Olfr193
NA
NA
NA
0.00
0.00
NA
NA
0.02

Olfr194
0.04
0.06
0.04
0.06
0.08
0.06
0.08
0.13

Olfr195
0.06
0.08
0.08
0.09
0.07
0.10
0.11
0.16

Olfr196
NA
NA
NA
NA
−0.01
NA
NA
NA

Olfr197
0.16
0.17
0.15
0.18
0.15
0.22
0.18
0.28

Olfr198
0.09
0.11
0.12
0.12
0.16
0.15
0.16
0.17

Olfr199
0.03
0.04
0.03
0.04
0.04
0.06
0.05
0.06

Olfr2
0.06
0.07
0.08
0.12
0.09
0.13
0.11
0.15

Olfr20
0.14
0.18
0.17
0.21
0.19
0.19
0.18
0.17

Olfr201
0.05
0.06
0.06
0.09
0.08
0.07
0.09
0.08

Olfr202
0.12
0.17
0.15
0.18
0.16
0.18
0.14
0.25

Olfr203
NA
NA
NA
NA
0.00
0.03
0.01
0.04

Olfr204
0.06
0.10
0.08
0.11
0.13
0.09
0.10
0.11

Olfr205
0.06
0.10
0.08
0.11
0.13
0.09
0.10
0.11

Olfr206
NA
0.03
0.02
0.02
0.02
0.02
0.03
0.09

Olfr207
0.10
0.12
0.07
0.11
0.12
0.11
0.07
0.15

Olfr208
0.10
0.12
0.07
0.11
0.12
0.11
0.07
0.15

Olfr209
0.10
0.12
0.07
0.11
0.12
0.11
0.07
0.15

Olfr211
0.21
0.25
0.22
0.26
0.24
0.28
0.26
0.24

Olfr212
0.17
0.20
0.17
0.20
0.21
0.22
0.23
0.19

Olfr213
0.23
0.27
0.22
0.27
0.26
0.23
0.25
0.25

Olfr214
0.25
0.31
0.27
0.30
0.29
0.32
0.29
0.29

Olfr215
0.23
0.25
0.23
0.31
0.29
0.27
0.29
0.33

Olfr218
0.09
0.11
0.09
0.11
0.11
0.13
0.12
0.08

Olfr220
0.24
0.26
0.26
0.26
0.26
0.25
0.26
0.24

Olfr221
0.25
0.30
0.29
0.33
0.30
0.30
0.30
0.35

Olfr222
0.32
0.38
0.33
0.39
0.41
0.38
0.38
0.39

Olfr223
0.16
0.20
0.18
0.22
0.22
0.22
0.22
0.29

Olfr224
0.03
0.02
0.02
0.08
0.02
0.05
0.06
0.07

Olfr225
0.27
0.31
0.26
0.32
0.30
0.31
0.30
0.26

Olfr228
0.02
0.04
0.02
0.04
0.02
0.03
0.06
0.12

Olfr229
0.03
0.03
0.02
0.04
0.02
0.00
0.02
0.04

Olfr23
0.17
0.20
0.15
0.18
0.18
0.20
0.16
0.19

Olfr231
0.24
0.30
0.26
0.30
0.28
0.30
0.25
0.30

Olfr235
0.09
0.15
0.14
0.14
0.11
0.13
0.17
0.17

Olfr237-ps1
0.08
0.13
0.09
0.14
0.15
0.11
0.09
0.13

Olfr239
0.50
0.62
0.56
0.63
0.59
0.60
0.54
0.65

Olfr24
0.17
0.22
0.19
0.22
0.19
0.22
0.20
0.25

Olfr242
0.04
0.07
0.06
0.08
0.09
0.07
0.11
0.09

Olfr243
NA
NA
NA
NA
0.00
0.04
NA
0.04

Olfr247
0.22
0.27
0.24
0.26
0.27
0.31
0.26
0.28

Olfr248
0.08
0.10
0.09
0.11
0.11
0.13
0.08
0.12

Olfr25
0.06
0.10
0.07
0.10
0.12
0.09
0.09
0.15

Olfr250
0.11
0.15
0.13
0.14
0.14
0.17
0.16
0.14

Olfr251
0.11
0.15
0.12
0.16
0.15
0.16
0.13
0.12

Olfr255
0.14
0.18
0.17
0.21
0.19
0.19
0.18
0.17

Olfr257
0.27
0.30
0.27
0.32
0.32
0.30
0.30
0.26

Olfr259
0.00
0.02
0.02
0.03
0.04
0.04
0.01
0.06

Olfr26
0.13
0.16
0.14
0.16
0.14
0.14
0.13
0.16

Olfr262
0.12
0.17
0.14
0.17
0.16
0.19
0.16
0.16

Olfr263
0.02
0.04
0.04
0.04
0.05
0.04
0.07
0.12

Olfr266
0.16
0.18
0.18
0.17
0.19
0.25
0.19
0.19

Olfr267
0.32
0.34
0.30
0.35
0.32
0.34
0.30
0.32

Olfr27
0.04
0.07
0.06
0.08
0.09
0.07
0.11
0.09

Olfr270
0.09
0.11
0.10
0.12
0.13
0.16
0.14
0.14

Olfr272
0.19
0.20
0.19
0.24
0.21
0.23
0.19
0.24

Olfr273
0.14
0.16
0.15
0.19
0.18
0.21
0.16
0.16

Olfr275
0.15
0.19
0.17
0.18
0.18
0.18
0.17
0.17

Olfr279
0.27
0.32
0.30
0.35
0.36
0.36
0.31
0.38

Olfr281
0.25
0.28
0.25
0.32
0.27
0.28
0.26
0.32

Olfr282
0.34
0.40
0.35
0.43
0.41
0.40
0.40
0.38

Olfr283
0.24
0.29
0.27
0.27
0.32
0.27
0.28
0.28

Olfr284
0.27
0.31
0.30
0.39
0.32
0.35
0.34
0.37

Olfr285
0.27
0.30
0.27
0.32
0.32
0.30
0.30
0.26

Olfr286
0.19
0.22
0.18
0.23
0.22
0.19
0.22
0.24

Olfr288
0.15
0.16
0.22
0.22
0.15
0.24
0.22
0.19

Olfr29-ps1
0.25
0.30
0.29
0.32
0.28
0.29
0.28
0.27

Olfr290
0.04
0.05
0.03
0.04
0.05
0.08
0.05
0.07

Olfr291
0.06
0.09
0.04
0.07
0.08
0.06
0.07
0.09

Olfr292
0.05
0.06
0.05
0.08
0.08
0.11
0.06
0.08

Olfr293
0.11
0.14
0.12
0.13
0.13
0.13
0.12
0.15

Olfr294
0.07
0.11
0.10
0.10
0.11
0.10
0.13
0.17

Olfr295
0.00
0.02
0.01
0.02
0.02
0.05
0.01
0.06

Olfr297
0.08
0.10
0.11
0.13
0.11
0.12
0.16
0.14

Olfr298
0.06
0.08
0.07
0.09
0.08
0.09
0.07
0.08

Olfr299
NA
NA
NA
NA
−0.04
NA
NA
0.03

Olfr3
0.18
0.25
0.20
0.25
0.21
0.25
0.22
0.25

Olfr30
0.31
0.36
0.30
0.44
0.40
0.36
0.34
0.37

Olfr301
0.05
0.06
0.06
0.07
0.07
0.08
0.07
0.15

Olfr303
0.11
0.15
0.11
0.15
0.19
0.17
0.14
0.21

Olfr304
0.06
0.07
0.07
0.10
0.09
0.10
0.11
0.16

Olfr305
0.12
0.15
0.17
0.18
0.19
0.22
0.19
0.21

Olfr307
0.15
0.18
0.16
0.21
0.20
0.18
0.20
0.29

Olfr308
0.07
0.09
0.08
0.07
0.10
0.11
0.10
0.11

Olfr309
0.19
0.21
0.21
0.22
0.21
0.21
0.21
0.22

Olfr31
0.23
0.26
0.24
0.28
0.28
0.30
0.27
0.27

Olfr310
0.05
0.04
0.04
0.09
0.08
0.10
0.10
0.13

Olfr311
0.14
0.15
0.14
0.20
0.17
0.19
0.17
0.20

Olfr312
0.19
0.22
0.18
0.24
0.23
0.23
0.20
0.25

Olfr313
0.16
0.20
0.19
0.20
0.21
0.20
0.17
0.17

Olfr314
0.41
0.49
0.43
0.53
0.48
0.50
0.47
0.46

Olfr315
0.30
0.32
0.32
0.38
0.38
0.37
0.35
0.34

Olfr316
0.36
0.37
0.37
0.42
0.42
0.41
0.37
0.31

Olfr317
0.27
0.30
0.29
0.33
0.28
0.31
0.30
0.29

Olfr318
0.18
0.19
0.16
0.20
0.20
0.22
0.21
0.22

Olfr319
0.19
0.25
0.19
0.24
0.25
0.24
0.21
0.22

Olfr32
0.08
0.09
0.09
0.09
0.09
0.12
0.09
0.09

Olfr320
0.26
0.31
0.32
0.35
0.32
0.36
0.31
0.33

Olfr322
0.33
0.34
0.35
0.39
0.38
0.38
0.38
0.43

Olfr323
0.12
0.15
0.13
0.19
0.16
0.14
0.13
0.23

Olfr324
0.20
0.24
0.20
0.27
0.29
0.26
0.27
0.22

Olfr325
0.08
0.11
0.09
0.14
0.15
0.11
0.11
0.16

Olfr328
0.24
0.28
0.27
0.33
0.32
0.32
0.31
0.37

Olfr329-ps
0.26
0.32
0.29
0.34
0.29
0.33
0.30
0.29

Olfr33
0.16
0.22
0.18
0.23
0.22
0.26
0.20
0.25

Olfr330
0.25
0.30
0.27
0.29
0.26
0.29
0.28
0.30

Olfr331
0.26
0.32
0.29
0.34
0.29
0.33
0.30
0.29

Olfr332
0.24
0.33
0.27
0.35
0.34
0.32
0.30
0.31

Olfr338
0.04
0.05
0.04
0.07
0.10
0.10
0.08
0.14

Olfr339
0.02
0.03
0.04
0.03
0.04
0.07
0.05
0.11

Olfr340
0.01
0.05
0.03
0.04
0.06
0.06
0.02
0.11

Olfr341
0.13
0.17
0.15
0.21
0.21
0.20
0.18
0.17

Olfr342
0.06
0.10
0.09
0.09
0.10
0.11
0.12
0.18

Olfr344
0.08
0.12
0.07
0.08
0.12
0.13
0.11
0.13

Olfr345
0.05
0.07
0.06
0.09
0.04
0.06
0.06
0.10

Olfr346
0.08
0.11
0.09
0.12
0.12
0.11
0.11
0.14

Olfr347
0.10
0.12
0.09
0.15
0.13
0.15
0.13
0.14

Olfr348
0.07
0.09
0.09
0.11
0.12
0.13
0.11
0.11

Olfr350
0.08
0.12
0.12
0.13
0.11
0.11
0.12
0.13

Olfr351
0.21
0.25
0.21
0.25
0.23
0.26
0.24
0.24

Olfr352
0.12
0.16
0.15
0.20
0.16
0.18
0.15
0.20

Olfr353
0.11
0.15
0.13
0.13
0.14
0.17
0.14
0.20

Olfr354
0.16
0.20
0.20
0.22
0.19
0.24
0.19
0.21

Olfr355
0.08
0.08
0.08
0.11
0.10
0.08
0.07
0.11

Olfr356
0.14
0.16
0.18
0.17
0.17
0.16
0.19
0.16

Olfr357
0.11
0.14
0.13
0.16
0.14
0.15
0.14
0.15

Olfr358
0.07
0.10
0.08
0.11
0.10
0.11
0.10
0.07

Olfr360
0.07
0.10
0.08
0.11
0.10
0.11
0.10
0.07

Olfr361
0.18
0.19
0.17
0.23
0.23
0.21
0.19
0.24

Olfr362
0.26
0.30
0.28
0.33
0.30
0.31
0.29
0.30

Olfr365
0.24
0.28
0.28
0.34
0.33
0.33
0.31
0.30

Olfr366
0.19
0.22
0.21
0.26
0.24
0.25
0.22
0.24

Olfr367-ps
0.24
0.27
0.25
0.29
0.26
0.32
0.28
0.27

Olfr368
0.33
0.36
0.34
0.38
0.39
0.37
0.34
0.38

Olfr370
0.26
0.30
0.27
0.34
0.33
0.32
0.28
0.32

Olfr371
0.24
0.28
0.27
0.30
0.28
0.31
0.28
0.32

Olfr372
0.32
0.37
0.33
0.39
0.36
0.39
0.34
0.39

Olfr373
0.27
0.35
0.28
0.36
0.37
0.37
0.33
0.43

Olfr374
0.21
0.25
0.21
0.22
0.28
0.26
0.24
0.27

Olfr376
0.15
0.19
0.18
0.19
0.19
0.22
0.19
0.20

Olfr378
0.05
0.05
0.05
0.08
0.07
0.08
0.09
0.12

Olfr38
0.22
0.24
0.23
0.25
0.23
0.27
0.23
0.27

Olfr380
0.02
0.06
0.03
0.08
0.07
0.07
0.05
0.13

Olfr381
0.11
0.15
0.15
0.15
0.16
0.15
0.12
0.19

Olfr382
0.12
0.15
0.13
0.15
0.15
0.14
0.17
0.20

Olfr384
0.05
0.09
0.06
0.09
0.09
0.10
0.10
0.09

Olfr385
0.04
0.05
0.05
0.06
0.06
0.09
0.06
0.09

Olfr389
0.11
0.14
0.14
0.15
0.13
0.14
0.11
0.16

Olfr39
0.19
0.24
0.23
0.24
0.25
0.26
0.24
0.28

Olfr390
0.09
0.12
0.10
0.11
0.11
0.14
0.10
0.08

Olfr391-ps
0.14
0.18
0.17
0.21
0.19
0.19
0.18
0.17

Olfr392
0.03
0.05
0.04
0.04
0.05
0.07
0.06
0.09

Olfr393
0.05
0.07
0.08
0.07
0.08
0.11
0.10
0.08

Olfr394
0.11
0.14
0.11
0.15
0.16
0.14
0.11
0.15

Olfr395
0.14
0.18
0.17
0.21
0.19
0.19
0.18
0.17

Olfr397
0.10
0.14
0.11
0.12
0.12
0.12
0.15
0.16

Olfr398
0.31
0.36
0.32
0.35
0.35
0.35
0.33
0.35

Olfr399
0.21
0.26
0.23
0.27
0.25
0.24
0.23
0.24

Olfr401
0.37
0.44
0.40
0.48
0.47
0.42
0.39
0.41

Olfr402
0.21
0.28
0.24
0.28
0.25
0.26
0.24
0.28

Olfr403
0.17
0.21
0.16
0.23
0.20
0.23
0.21
0.22

Olfr406
0.20
0.24
0.20
0.28
0.25
0.26
0.26
0.26

Olfr410
0.15
0.18
0.16
0.18
0.22
0.20
0.16
0.20

Olfr411
0.32
0.38
0.34
0.44
0.38
0.39
0.36
0.38

Olfr412
0.29
0.35
0.31
0.34
0.34
0.36
0.34
0.34

Olfr414
0.25
0.26
0.26
0.29
0.29
0.29
0.28
0.30

Olfr417
0.30
0.34
0.33
0.35
0.36
0.32
0.34
0.35

Olfr418
0.15
0.19
0.17
0.20
0.19
0.20
0.20
0.22

Olfr419
0.24
0.27
0.23
0.27
0.29
0.29
0.28
0.22

Olfr420
0.19
0.22
0.23
0.25
0.23
0.22
0.23
0.20

Olfr421-ps1
0.10
0.13
0.13
0.14
0.15
0.16
0.18
0.21

Olfr424
0.19
0.25
0.23
0.26
0.24
0.26
0.21
0.28

Olfr426
0.11
0.15
0.15
0.14
0.14
0.17
0.16
0.14

Olfr427
0.11
0.15
0.15
0.14
0.14
0.17
0.16
0.14

Olfr429
0.16
0.21
0.17
0.24
0.23
0.21
0.22
0.19

Olfr43
0.01
0.06
0.06
0.06
0.07
0.05
0.08
0.10

Olfr430
0.09
0.13
0.13
0.13
0.11
0.13
0.09
0.12

Olfr432
0.15
0.18
0.18
0.20
0.16
0.18
0.19
0.17

Olfr433
0.29
0.31
0.28
0.33
0.31
0.29
0.27
0.31

Olfr434
0.20
0.20
0.20
0.23
0.24
0.24
0.20
0.26

Olfr435
0.29
0.32
0.29
0.35
0.33
0.33
0.30
0.35

Olfr437
0.19
0.23
0.21
0.24
0.23
0.26
0.21
0.24

Olfr44
0.03
0.05
0.05
0.06
0.06
0.05
0.05
0.05

Olfr441
0.21
0.25
0.24
0.27
0.25
0.27
0.23
0.23

Olfr444
0.24
0.29
0.26
0.33
0.32
0.31
0.35
0.38

Olfr446
0.14
0.16
0.13
0.17
0.20
0.20
0.20
0.24

Olfr447
0.22
0.28
0.23
0.29
0.25
0.25
0.26
0.25

Olfr448
0.20
0.24
0.20
0.24
0.23
0.25
0.19
0.27

Olfr449
0.17
0.16
0.18
0.20
0.21
0.22
0.22
0.18

Olfr45
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr450
0.19
0.24
0.22
0.23
0.21
0.26
0.24
0.20

Olfr452
0.05
0.05
0.05
0.05
0.03
0.05
0.10
0.07

Olfr453
0.18
0.20
0.18
0.21
0.21
0.20
0.23
0.20

Olfr455
0.20
0.21
0.22
0.22
0.23
0.24
0.24
0.23

Olfr456
0.25
0.34
0.31
0.33
0.32
0.34
0.29
0.36

Olfr457
0.25
0.34
0.31
0.33
0.32
0.34
0.29
0.36

Olfr458
0.26
0.33
0.31
0.37
0.32
0.36
0.31
0.38

Olfr459
0.22
0.27
0.22
0.27
0.24
0.28
0.27
0.28

Olfr46
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr460
0.14
0.16
0.14
0.18
0.17
0.17
0.16
0.16

Olfr461
0.10
0.12
0.09
0.16
0.10
0.15
0.10
0.13

Olfr462
0.37
0.48
0.40
0.46
0.46
0.42
0.43
0.42

Olfr463
0.27
0.31
0.28
0.38
0.36
0.35
0.35
0.31

Olfr464
0.29
0.34
0.32
0.37
0.39
0.36
0.35
0.37

Olfr466
0.08
0.11
0.09
0.11
0.13
0.12
0.09
0.11

Olfr467
0.21
0.27
0.23
0.25
0.24
0.28
0.24
0.24

Olfr469
0.09
0.11
0.11
0.13
0.15
0.13
0.16
0.20

Olfr47
0.16
0.20
0.17
0.20
0.23
0.21
0.24
0.24

Olfr470
0.09
0.10
0.08
0.11
0.12
0.13
0.10
0.15

Olfr472
NA
0.00
NA
NA
−0.01
NA
0.01
0.02

Olfr473
0.08
0.10
0.09
0.10
0.14
0.12
0.11
0.14

Olfr474
0.02
0.04
0.03
0.05
0.03
0.03
0.06
0.08

Olfr476
0.14
0.18
0.16
0.17
0.15
0.22
0.16
0.19

Olfr477
0.22
0.25
0.23
0.28
0.24
0.26
0.25
0.26

Olfr478
0.08
0.11
0.10
0.10
0.11
0.14
0.11
0.16

Olfr479
0.24
0.25
0.24
0.25
0.26
0.25
0.25
0.24

Olfr48
0.34
0.38
0.37
0.39
0.38
0.39
0.37
0.39

Olfr480
0.02
0.01
0.02
0.01
0.03
0.03
0.01
0.06

Olfr481
0.15
0.16
0.16
0.17
0.17
0.18
0.16
0.20

Olfr482
0.08
0.12
0.12
0.14
0.15
0.11
0.15
0.16

Olfr483
0.15
0.19
0.17
0.18
0.20
0.20
0.19
0.19

Olfr484
0.13
0.14
0.15
0.14
0.16
0.14
0.16
0.18

Olfr485
0.21
0.25
0.24
0.26
0.28
0.25
0.24
0.34

Olfr486
0.15
0.19
0.17
0.20
0.19
0.20
0.18
0.26

Olfr487
0.15
0.19
0.17
0.20
0.19
0.20
0.18
0.26

Olfr488
0.08
0.13
0.11
0.12
0.12
0.15
0.13
0.14

Olfr49
0.12
0.16
0.14
0.15
0.19
0.17
0.15
0.17

Olfr490
NA
0.02
NA
0.02
0.00
0.00
NA
0.05

Olfr491
0.15
0.20
0.15
0.19
0.17
0.19
0.15
0.20

Olfr492
0.09
0.13
0.11
0.14
0.14
0.14
0.14
0.15

Olfr493
0.07
0.09
0.09
0.12
0.09
0.11
0.11
0.18

Olfr494
0.13
0.16
0.15
0.18
0.16
0.17
0.16
0.18

Olfr495
0.09
0.11
0.13
0.11
0.11
0.14
0.09
0.15

Olfr497
0.06
0.10
0.11
0.10
0.10
0.13
0.15
0.15

Olfr498
0.08
0.10
0.09
0.11
0.11
0.12
0.12
0.13

Olfr5
0.24
0.31
0.27
0.35
0.29
0.28
0.26
0.29

Olfr50
0.06
0.09
0.11
0.10
0.14
0.08
0.14
0.05

Olfr502
0.13
0.17
0.13
0.13
0.16
0.16
0.15
0.13

Olfr503
0.21
0.29
0.23
0.25
0.26
0.27
0.26
0.27

Olfr504
0.07
0.08
0.09
0.12
0.10
0.12
0.12
0.14

Olfr506
0.08
0.12
0.12
0.14
0.15
0.11
0.15
0.16

Olfr507
0.08
0.12
0.12
0.14
0.15
0.11
0.15
0.16

Olfr508
0.11
0.18
0.13
0.13
0.20
0.17
0.14
0.16

Olfr509
0.05
0.06
0.04
0.07
0.10
0.07
0.07
0.11

Olfr51
0.24
0.26
0.26
0.27
0.27
0.26
0.27
0.31

Olfr510
0.09
0.09
0.07
0.11
0.09
0.11
0.12
0.17

Olfr512
0.02
0.04
0.05
0.05
0.07
0.06
0.04
0.11

Olfr513
0.19
0.24
0.23
0.23
0.26
0.25
0.24
0.22

Olfr514
0.21
0.28
0.25
0.28
0.24
0.30
0.27
0.27

Olfr516
0.02
0.06
0.04
0.10
0.09
0.06
0.09
0.11

Olfr517
0.18
0.21
0.20
0.24
0.22
0.22
0.19
0.28

Olfr518
0.08
0.13
0.10
0.12
0.12
0.10
0.13
0.13

Olfr519
0.08
0.13
0.10
0.12
0.12
0.10
0.13
0.13

Olfr52
0.17
0.20
0.19
0.20
0.21
0.20
0.21
0.27

Olfr520
0.18
0.22
0.21
0.22
0.25
0.24
0.24
0.27

Olfr521
0.12
0.20
0.12
0.19
0.22
0.17
0.13
0.18

Olfr522
0.33
0.37
0.34
0.36
0.36
0.39
0.37
0.36

Olfr523
0.28
0.35
0.31
0.37
0.36
0.36
0.32
0.32

Olfr524
0.40
0.48
0.43
0.49
0.48
0.48
0.46
0.45

Olfr525
0.20
0.22
0.20
0.25
0.26
0.25
0.23
0.25

Olfr527
0.23
0.26
0.26
0.29
0.26
0.32
0.26
0.24

Olfr53
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr530
0.27
0.33
0.28
0.34
0.32
0.36
0.30
0.27

Olfr531
0.18
0.17
0.17
0.20
0.21
0.21
0.18
0.22

Olfr532
0.22
0.26
0.24
0.28
0.27
0.28
0.24
0.26

Olfr533
0.27
0.33
0.28
0.34
0.32
0.36
0.30
0.27

Olfr535
0.34
0.40
0.35
0.42
0.40
0.39
0.38
0.37

Olfr536
0.27
0.33
0.28
0.34
0.32
0.36
0.30
0.27

Olfr538
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr539
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr54
0.35
0.43
0.39
0.46
0.42
0.43
0.40
0.43

Olfr541
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr543
0.35
0.36
0.36
0.39
0.38
0.41
0.38
0.35

Olfr544
0.18
0.22
0.19
0.24
0.27
0.21
0.19
0.15

Olfr545
0.38
0.44
0.40
0.44
0.46
0.45
0.43
0.47

Olfr547
0.13
0.16
0.13
0.18
0.17
0.16
0.18
0.22

Olfr549
0.26
0.32
0.29
0.35
0.31
0.35
0.33
0.33

Olfr55
0.26
0.35
0.29
0.36
0.33
0.35
0.30
0.30

Olfr550
0.32
0.35
0.31
0.38
0.36
0.39
0.34
0.37

Olfr551
0.19
0.22
0.18
0.24
0.24
0.26
0.21
0.22

Olfr552
0.21
0.22
0.20
0.25
0.20
0.22
0.25
0.23

Olfr553
0.16
0.18
0.18
0.20
0.19
0.19
0.20
0.17

Olfr554
0.20
0.22
0.21
0.24
0.23
0.25
0.24
0.23

Olfr555
0.19
0.21
0.21
0.24
0.23
0.25
0.23
0.26

Olfr556
0.16
0.20
0.18
0.21
0.20
0.22
0.19
0.22

Olfr557
0.15
0.20
0.16
0.21
0.20
0.20
0.18
0.26

Olfr558
0.23
0.25
0.22
0.26
0.26
0.28
0.25
0.24

Olfr559
0.09
0.12
0.13
0.14
0.19
0.12
0.11
0.18

Olfr56
0.23
0.39
0.47
0.28
0.20
0.34
0.46
0.49

Olfr560
0.07
0.10
0.08
0.11
0.12
0.11
0.10
0.14

Olfr561
0.10
0.15
0.13
0.14
0.14
0.13
0.13
0.13

Olfr564
0.07
0.07
0.06
0.11
0.10
0.10
0.11
0.13

Olfr566
0.24
0.34
0.35
0.40
0.38
0.40
0.38
0.46

Olfr568
0.15
0.19
0.15
0.21
0.19
0.18
0.18
0.23

Olfr569
0.16
0.20
0.16
0.21
0.21
0.24
0.21
0.23

Olfr57
0.03
0.07
0.06
0.07
0.09
0.09
0.08
0.11

Olfr570
0.10
0.10
0.12
0.12
0.12
0.15
0.15
0.13

Olfr571
0.20
0.28
0.25
0.27
0.24
0.29
0.27
0.23

Olfr572
0.17
0.22
0.20
0.23
0.21
0.22
0.22
0.23

Olfr574
0.14
0.15
0.16
0.18
0.16
0.17
0.17
0.14

Olfr575
0.17
0.15
0.16
0.15
0.17
0.19
0.14
0.18

Olfr576
0.16
0.21
0.21
0.21
0.20
0.25
0.25
0.17

Olfr577
0.20
0.24
0.24
0.24
0.23
0.29
0.20
0.21

Olfr578
0.08
0.09
0.08
0.10
0.12
0.10
0.11
0.16

Olfr58
0.00
0.01
0.01
0.00
0.01
0.01
0.02
0.07

Olfr582
0.24
0.29
0.26
0.30
0.28
0.34
0.28
0.29

Olfr583
0.04
0.05
0.04
0.06
0.06
0.08
0.07
0.13

Olfr584
0.12
0.14
0.14
0.18
0.16
0.15
0.14
0.23

Olfr585
0.04
0.05
0.04
0.06
0.06
0.08
0.07
0.13

Olfr586
0.21
0.22
0.20
0.24
0.24
0.27
0.24
0.24

Olfr589
0.18
0.20
0.20
0.21
0.21
0.22
0.23
0.28

Olfr59
0.21
0.25
0.23
0.24
0.25
0.26
0.27
0.26

Olfr591
0.09
0.11
0.12
0.09
0.13
0.12
0.10
0.14

Olfr592
0.08
0.11
0.08
0.12
0.09
0.14
0.09
0.16

Olfr593
0.13
0.18
0.14
0.17
0.17
0.15
0.16
0.19

Olfr594
0.17
0.23
0.21
0.25
0.24
0.24
0.19
0.22

Olfr596
0.12
0.16
0.14
0.17
0.18
0.16
0.17
0.17

Olfr597
NA
0.03
0.06
0.03
0.05
0.07
0.05
0.11

Olfr598
0.16
0.16
0.16
0.20
0.21
0.19
0.19
0.38

Olfr599
0.13
0.14
0.10
0.15
0.16
0.18
0.14
0.18

Olfr6
0.21
0.23
0.22
0.24
0.25
0.29
0.22
0.25

Olfr60
0.10
0.11
0.08
0.12
0.14
0.14
0.13
0.17

Olfr600
0.11
0.17
0.12
0.13
0.16
0.13
0.14
0.11

Olfr601
0.26
0.31
0.29
0.33
0.32
0.31
0.31
0.35

Olfr603
0.08
0.09
0.10
0.17
0.14
0.14
0.12
0.17

Olfr605
0.21
0.24
0.19
0.33
0.26
0.27
0.26
0.25

Olfr606
0.08
0.10
0.09
0.10
0.11
0.12
0.10
0.13

Olfr607
0.13
0.14
0.16
0.15
0.17
0.19
0.15
0.19

Olfr608
0.25
0.31
0.27
0.31
0.31
0.31
0.30
0.24

Olfr609
0.24
0.29
0.27
0.29
0.28
0.29
0.28
0.28

Olfr61
0.22
0.29
0.24
0.31
0.27
0.30
0.28
0.26

Olfr610
0.25
0.30
0.30
0.32
0.30
0.31
0.32
0.32

Olfr611
0.15
0.16
0.11
0.18
0.14
0.19
0.16
0.17

Olfr612
0.09
0.10
0.11
0.14
0.11
0.13
0.11
0.16

Olfr613
0.12
0.14
0.12
0.14
0.14
0.13
0.13
0.12

Olfr615
0.13
0.14
0.13
0.16
0.15
0.16
0.16
0.21

Olfr616
0.14
0.18
0.16
0.19
0.20
0.20
0.17
0.19

Olfr617
0.08
0.13
0.09
0.11
0.11
0.10
0.11
0.11

Olfr618
0.04
0.06
0.05
0.06
0.06
0.07
0.05
0.09

Olfr619
0.07
0.08
0.08
0.10
0.10
0.09
0.09
0.08

Olfr62
0.16
0.19
0.19
0.23
0.22
0.21
0.20
0.22

Olfr620
0.13
0.17
0.14
0.18
0.16
0.21
0.14
0.17

Olfr622
0.12
0.13
0.13
0.17
0.17
0.19
0.18
0.20

Olfr623
0.13
0.11
0.10
0.12
0.14
0.14
0.09
0.17

Olfr624
0.05
0.05
0.05
0.07
0.08
0.04
0.04
0.07

Olfr628
0.02
0.02
0.02
0.02
0.04
0.02
0.01
0.07

Olfr629
0.11
0.12
0.12
0.13
0.12
0.13
0.11
0.15

Olfr63
0.30
0.31
0.30
0.36
0.36
0.34
0.34
0.31

Olfr630
0.07
0.09
0.07
0.09
0.09
0.11
0.08
0.14

Olfr631
0.05
0.07
0.06
0.08
0.07
0.10
0.06
0.09

Olfr632
0.30
0.33
0.30
0.34
0.34
0.36
0.31
0.33

Olfr633
0.24
0.27
0.24
0.32
0.25
0.28
0.29
0.28

Olfr635
0.18
0.23
0.19
0.24
0.20
0.22
0.20
0.20

Olfr638
0.23
0.28
0.25
0.27
0.28
0.31
0.30
0.27

Olfr639
0.13
0.17
0.15
0.19
0.14
0.16
0.18
0.19

Olfr64
0.13
0.15
0.13
0.19
0.15
0.16
0.16
0.17

Olfr640
0.14
0.14
0.15
0.18
0.16
0.18
0.16
0.19

Olfr641
0.18
0.22
0.19
0.24
0.22
0.21
0.23
0.22

Olfr642
0.21
0.26
0.22
0.25
0.24
0.24
0.27
0.25

Olfr643
0.06
0.10
0.08
0.09
0.11
0.10
0.12
0.13

Olfr644
0.16
0.18
0.17
0.19
0.20
0.20
0.18
0.22

Olfr645
0.23
0.28
0.24
0.27
0.26
0.29
0.25
0.26

Olfr646
0.25
0.29
0.24
0.29
0.29
0.31
0.27
0.29

Olfr648
0.19
0.23
0.21
0.24
0.24
0.24
0.22
0.23

Olfr649
0.14
0.15
0.14
0.18
0.19
0.18
0.18
0.21

Olfr65
0.09
0.11
0.09
0.11
0.11
0.11
0.13
0.19

Olfr651
0.20
0.24
0.21
0.22
0.21
0.22
0.22
0.22

Olfr652
0.19
0.22
0.20
0.22
0.20
0.24
0.21
0.20

Olfr653
0.21
0.26
0.25
0.25
0.25
0.28
0.26
0.23

Olfr654
0.12
0.18
0.12
0.15
0.13
0.17
0.12
0.13

Olfr655
0.14
0.18
0.15
0.17
0.15
0.17
0.17
0.19

Olfr656
0.22
0.30
0.25
0.26
0.28
0.28
0.27
0.27

Olfr657
0.19
0.26
0.21
0.23
0.23
0.23
0.23
0.23

Olfr658
0.29
0.36
0.31
0.35
0.34
0.32
0.33
0.36

Olfr659
0.11
0.14
0.14
0.18
0.15
0.17
0.21
0.15

Olfr66
0.07
0.11
0.10
0.09
0.09
0.14
0.11
0.10

Olfr661
0.16
0.17
0.17
0.18
0.19
0.18
0.17
0.17

Olfr663
0.13
0.16
0.16
0.16
0.18
0.14
0.16
0.17

Olfr665
0.04
0.08
0.08
0.06
0.08
0.11
0.05
0.10

Olfr666
0.18
0.24
0.21
0.21
0.21
0.26
0.22
0.21

Olfr667
0.18
0.21
0.19
0.20
0.21
0.20
0.20
0.26

Olfr668
0.07
0.11
0.07
0.10
0.10
0.13
0.09
0.10

Olfr669
0.23
0.25
0.25
0.27
0.27
0.27
0.26
0.32

Olfr67
0.02
0.04
0.04
0.07
0.04
0.07
0.08
0.12

Olfr670
0.19
0.22
0.20
0.24
0.21
0.24
0.22
0.29

Olfr671
0.11
0.17
0.15
0.17
0.20
0.14
0.16
0.15

Olfr672
0.11
0.14
0.13
0.16
0.14
0.19
0.16
0.16

Olfr675
0.06
0.09
0.08
0.09
0.09
0.05
0.11
0.11

Olfr676
0.08
0.11
0.09
0.11
0.12
0.15
0.13
0.14

Olfr677
0.09
0.09
0.11
0.14
0.12
0.13
0.11
0.13

Olfr678
0.29
0.35
0.31
0.36
0.32
0.36
0.33
0.35

Olfr679
0.07
0.09
0.09
0.09
0.11
0.12
0.09
0.12

Olfr68
0.12
0.14
0.13
0.18
0.15
0.14
0.14
0.16

Olfr681
0.07
0.09
0.09
0.09
0.11
0.12
0.09
0.12

Olfr683
0.10
0.14
0.11
0.12
0.15
0.15
0.16
0.13

Olfr684
0.09
0.12
0.09
0.14
0.14
0.15
0.15
0.19

Olfr685
0.20
0.21
0.21
0.24
0.21
0.21
0.23
0.20

Olfr686
0.24
0.27
0.24
0.27
0.28
0.27
0.25
0.26

Olfr688
0.12
0.17
0.14
0.17
0.16
0.17
0.18
0.17

Olfr689
0.20
0.26
0.20
0.25
0.26
0.24
0.25
0.28

Olfr69
0.01
0.01
0.00
0.03
0.02
0.01
0.04
0.04

Olfr690
0.20
0.26
0.24
0.28
0.26
0.24
0.25
0.25

Olfr691
0.19
0.21
0.20
0.22
0.24
0.24
0.19
0.24

Olfr692
0.24
0.27
0.26
0.29
0.27
0.30
0.27
0.25

Olfr693
0.20
0.25
0.20
0.27
0.24
0.28
0.20
0.26

Olfr694
0.17
0.21
0.16
0.19
0.21
0.23
0.18
0.19

Olfr695
0.12
0.16
0.12
0.15
0.14
0.16
0.14
0.17

Olfr697
0.22
0.25
0.21
0.25
0.22
0.25
0.22
0.22

Olfr698
0.18
0.20
0.21
0.24
0.22
0.22
0.22
0.25

Olfr699
0.14
0.20
0.17
0.18
0.18
0.21
0.21
0.16

Olfr70
0.30
0.35
0.31
0.34
0.34
0.34
0.34
0.35

Olfr700
0.18
0.20
0.20
0.23
0.22
0.20
0.22
0.21

Olfr701
0.07
0.12
0.07
0.13
0.12
0.10
0.07
0.13

Olfr702
0.05
0.09
0.07
0.09
0.10
0.10
0.08
0.12

Olfr703
0.16
0.20
0.19
0.19
0.19
0.20
0.20
0.19

Olfr704
0.11
0.15
0.12
0.16
0.17
0.14
0.18
0.14

Olfr705
0.11
0.16
0.13
0.18
0.17
0.15
0.15
0.16

Olfr706
0.18
0.19
0.19
0.21
0.20
0.21
0.18
0.24

Olfr707
0.09
0.09
0.11
0.16
0.16
0.10
0.13
0.20

Olfr71
0.43
0.49
0.46
0.51
0.46
0.48
0.50
0.53

Olfr710
0.21
0.25
0.22
0.27
0.23
0.27
0.24
0.27

Olfr711
0.22
0.25
0.24
0.28
0.25
0.27
0.24
0.32

Olfr713
0.22
0.27
0.25
0.28
0.28
0.27
0.27
0.26

Olfr714
0.22
0.26
0.25
0.25
0.28
0.24
0.24
0.27

Olfr715
0.05
0.07
0.07
0.08
0.08
0.08
0.09
0.15

Olfr716
0.14
0.15
0.13
0.18
0.17
0.16
0.16
0.13

Olfr720
0.17
0.21
0.18
0.20
0.18
0.21
0.16
0.21

Olfr722
0.00
0.01
NA
0.02
0.01
NA
0.01
0.06

Olfr723
0.19
0.24
0.22
0.24
0.21
0.22
0.26
0.21

Olfr724
0.19
0.24
0.22
0.24
0.21
0.22
0.26
0.21

Olfr725
0.09
0.11
0.08
0.11
0.15
0.13
0.09
0.18

Olfr726
0.04
0.08
0.05
0.08
0.08
0.10
0.08
0.16

Olfr727
0.05
0.06
0.05
0.08
0.07
0.05
0.08
0.15

Olfr728
0.10
0.14
0.13
0.16
0.15
0.19
0.15
0.15

Olfr729
0.07
0.08
0.07
0.08
0.07
0.11
0.07
0.10

Olfr73
0.14
0.18
0.16
0.21
0.23
0.26
0.17
0.20

Olfr730
0.10
0.10
0.13
0.14
0.14
0.18
0.16
0.17

Olfr731
0.08
0.10
0.07
0.09
0.10
0.10
0.08
0.12

Olfr732
0.09
0.11
0.09
0.10
0.11
0.12
0.11
0.13

Olfr733
0.08
0.12
0.10
0.09
0.10
0.14
0.12
0.12

Olfr734
0.18
0.22
0.17
0.23
0.20
0.23
0.23
0.25

Olfr735
0.14
0.17
0.17
0.21
0.17
0.17
0.18
0.20

Olfr736
0.20
0.23
0.21
0.24
0.22
0.24
0.23
0.24

Olfr738
0.17
0.18
0.19
0.18
0.16
0.20
0.20
0.24

Olfr739
NA
0.03
NA
NA
0.01
0.05
0.01
0.01

Olfr74
0.13
0.16
0.15
0.17
0.15
0.18
0.16
0.16

Olfr740
0.14
0.17
0.15
0.19
0.19
0.20
0.18
0.24

Olfr741
0.14
0.19
0.16
0.19
0.20
0.18
0.16
0.21

Olfr742
0.01
0.02
NA
0.03
0.03
0.02
0.08
0.03

Olfr743
0.08
0.11
0.09
0.12
0.12
0.14
0.11
0.20

Olfr744
0.23
0.22
0.21
0.26
0.25
0.26
0.24
0.24

Olfr745
0.24
0.27
0.25
0.30
0.26
0.30
0.30
0.27

Olfr746
0.06
0.07
0.08
0.05
0.08
0.13
0.07
0.11

Olfr747
0.02
0.04
0.01
0.03
0.05
0.03
0.07
0.06

Olfr748
0.07
0.10
0.09
0.08
0.12
0.11
0.10
0.15

Olfr749
0.03
0.05
0.03
0.04
0.03
0.06
0.04
0.06

Olfr750
0.26
0.29
0.26
0.30
0.29
0.28
0.28
0.27

Olfr76
0.21
0.27
0.21
0.24
0.23
0.24
0.21
0.21

Olfr761
0.09
0.09
0.08
0.10
0.11
0.09
0.11
0.13

Olfr763
0.16
0.20
0.15
0.20
0.23
0.19
0.18
0.25

Olfr765
0.25
0.26
0.25
0.29
0.24
0.30
0.26
0.25

Olfr767
0.53
0.54
0.47
0.62
0.57
0.51
0.42
0.46

Olfr768
0.01
0.02
0.02
0.05
0.05
0.02
0.05
0.10

Olfr769
0.13
0.17
0.14
0.20
0.19
0.21
0.15
0.19

Olfr77
0.07
0.11
0.11
0.12
0.11
0.13
0.11
0.12

Olfr770
0.19
0.26
0.22
0.27
0.21
0.24
0.22
0.22

Olfr771
0.05
0.08
0.08
0.06
0.10
0.09
0.08
0.15

Olfr772
0.04
0.08
0.05
0.07
0.08
0.09
0.08
0.05

Olfr773
0.08
0.11
0.11
0.10
0.14
0.12
0.11
0.13

Olfr774
0.22
0.26
0.23
0.26
0.26
0.30
0.26
0.27

Olfr775
0.07
0.08
0.09
0.10
0.14
0.13
0.07
0.18

Olfr776
0.01
0.04
0.01
0.03
0.04
0.06
0.02
0.03

Olfr777
0.04
0.05
0.05
0.05
0.05
0.05
0.04
0.10

Olfr78
0.07
0.10
0.08
0.11
0.12
0.11
0.10
0.14

Olfr780
0.09
0.11
0.09
0.12
0.12
0.11
0.11
0.14

Olfr781
0.03
0.05
0.03
0.05
0.07
0.06
0.06
0.15

Olfr782
0.07
0.09
0.08
0.09
0.12
0.10
0.09
0.13

Olfr784
0.12
0.18
0.16
0.15
0.17
0.18
0.20
0.22

Olfr786
0.07
0.11
0.09
0.13
0.10
0.08
0.09
0.10

Olfr787
NA
0.03
0.01
0.05
0.04
0.02
0.02
0.09

Olfr788
0.15
0.18
0.17
0.20
0.20
0.20
0.23
0.21

Olfr790
0.14
0.18
0.16
0.17
0.18
0.18
0.17
0.20

Olfr791
0.08
0.07
0.08
0.08
0.11
0.08
0.11
0.13

Olfr792
0.04
0.05
0.05
0.06
0.04
0.06
0.07
0.10

Olfr794
0.13
0.15
0.13
0.16
0.15
0.15
0.15
0.18

Olfr796
0.27
0.34
0.30
0.34
0.36
0.35
0.32
0.35

Olfr798
0.02
0.04
0.05
0.05
0.06
0.05
0.03
0.14

Olfr799
0.06
0.09
0.07
0.09
0.10
0.10
0.11
0.14

Olfr8
NA
0.03
0.02
0.04
0.03
0.02
0.06
0.11

Olfr800
0.04
0.05
0.05
0.05
0.05
0.05
0.04
0.10

Olfr801
0.12
0.17
0.14
0.14
0.15
0.15
0.14
0.15

Olfr802
0.05
0.08
0.06
0.08
0.08
0.07
0.09
0.08

Olfr803
0.02
0.03
0.05
0.02
0.04
0.04
0.03
0.10

Olfr804
0.07
0.09
0.08
0.09
0.12
0.10
0.09
0.13

Olfr805
0.06
0.10
0.07
0.07
0.08
0.11
0.10
0.10

Olfr806
NA
NA
NA
NA
−0.03
NA
0.02
NA

Olfr807
0.28
0.32
0.29
0.32
0.31
0.30
0.31
0.31

Olfr808
0.11
0.11
0.12
0.15
0.12
0.15
0.15
0.13

Olfr809
0.02
0.06
0.03
0.06
0.06
0.06
0.06
0.11

Olfr810
0.19
0.25
0.20
0.22
0.23
0.26
0.25
0.25

Olfr811
0.14
0.17
0.15
0.17
0.18
0.18
0.16
0.20

Olfr812
0.12
0.15
0.14
0.14
0.15
0.17
0.16
0.14

Olfr813
0.06
0.10
0.06
0.08
0.09
0.09
0.11
0.13

Olfr814
NA
0.01
0.00
0.01
0.01
NA
0.05
0.08

Olfr815
NA
0.01
0.00
0.01
0.02
0.03
0.04
0.06

Olfr816
0.04
0.05
0.03
0.05
0.07
0.06
0.07
0.09

Olfr818
0.08
0.09
0.09
0.10
0.10
0.10
0.10
0.11

Olfr819
0.22
0.27
0.24
0.26
0.27
0.31
0.26
0.28

Olfr820
0.05
0.06
0.06
0.09
0.08
0.07
0.07
0.07

Olfr821
0.09
0.11
0.11
0.12
0.13
0.14
0.11
0.14

Olfr822
0.05
0.09
0.07
0.09
0.08
0.09
0.10
0.13

Olfr823
0.03
0.04
0.04
0.04
0.05
0.04
0.07
0.11

Olfr824
0.03
0.04
0.04
0.04
0.05
0.04
0.07
0.11

Olfr825
0.12
0.16
0.12
0.15
0.14
0.14
0.14
0.23

Olfr826
0.00
0.01
0.02
0.05
0.06
0.02
0.04
0.11

Olfr827
0.05
0.06
0.04
0.07
0.06
0.07
0.09
0.08

Olfr828
0.08
0.09
0.10
0.12
0.11
0.07
0.12
0.14

Olfr829
0.09
0.14
0.11
0.12
0.13
0.14
0.12
0.16

Olfr830
0.09
0.12
0.12
0.12
0.10
0.15
0.16
0.12

Olfr832
0.02
0.05
0.03
0.05
0.05
0.04
0.04
0.11

Olfr834
NA
0.01
0.01
0.01
0.02
0.01
NA
0.08

Olfr835
0.16
0.14
0.18
0.19
0.14
0.21
0.16
0.18

Olfr836
0.01
0.05
0.02
0.03
0.02
0.05
0.09
0.12

Olfr837
NA
0.02
NA
0.02
0.03
0.02
0.06
0.14

Olfr843
0.09
0.14
0.13
0.12
0.14
0.14
0.15
0.14

Olfr845
0.13
0.17
0.14
0.17
0.14
0.14
0.13
0.16

Olfr846
0.00
0.03
0.01
0.01
0.03
0.03
0.04
0.08

Olfr847
0.01
0.03
0.01
0.06
0.05
0.06
0.05
0.10

Olfr849
0.00
0.03
NA
0.04
0.02
0.05
0.01
0.03

Olfr850
0.16
0.18
0.21
0.20
0.17
0.19
0.19
0.15

Olfr851
0.09
0.10
0.08
0.08
0.12
0.11
0.09
0.13

Olfr853
0.05
0.08
0.06
0.07
0.09
0.08
0.10
0.12

Olfr854
0.06
0.06
0.06
0.07
0.07
0.09
0.09
0.09

Olfr855
0.06
0.08
0.09
0.07
0.08
0.11
0.11
0.16

Olfr856-ps1
0.12
0.14
0.13
0.17
0.13
0.17
0.11
0.18

Olfr857
0.03
0.05
0.04
0.05
0.10
0.09
0.09
0.08

Olfr859
0.00
NA
NA
0.02
0.05
0.04
0.05
0.17

Olfr860
0.05
0.04
0.05
0.07
0.06
0.05
0.09
0.11

Olfr862
0.08
0.07
0.09
0.11
0.12
0.09
0.09
0.13

Olfr866
0.06
0.08
0.09
0.09
0.07
0.09
0.10
0.09

Olfr867
0.18
0.22
0.17
0.21
0.20
0.24
0.19
0.22

Olfr868
0.01
0.04
0.02
0.06
0.04
0.06
0.05
0.07

Olfr869
0.02
0.06
0.02
0.02
0.03
0.03
0.05
0.13

Olfr870
0.13
0.16
0.14
0.18
0.19
0.17
0.13
0.20

Olfr871
0.13
0.16
0.15
0.17
0.16
0.16
0.17
0.20

Olfr872
NA
0.01
0.01
0.01
0.03
0.03
0.05
0.10

Olfr873
0.07
0.08
0.06
0.08
0.09
0.09
0.08
0.11

Olfr874
0.22
0.25
0.24
0.24
0.28
0.27
0.26
0.27

Olfr875
0.15
0.14
0.16
0.16
0.16
0.18
0.19
0.16

Olfr876
0.14
0.17
0.14
0.16
0.20
0.18
0.16
0.15

Olfr877
0.07
0.10
0.07
0.13
0.13
0.13
0.11
0.15

Olfr878
0.17
0.20
0.18
0.19
0.19
0.20
0.22
0.19

Olfr881
0.04
0.07
0.05
0.09
0.08
0.08
0.09
0.08

Olfr883
0.03
0.06
0.03
0.06
0.07
0.05
0.04
0.06

Olfr884
0.03
0.06
0.03
0.06
0.07
0.05
0.04
0.06

Olfr885
0.03
0.06
0.03
0.06
0.07
0.05
0.04
0.06

Olfr887
0.03
0.06
0.03
0.06
0.07
0.05
0.04
0.06

Olfr888
0.05
0.06
0.07
0.07
0.07
0.11
0.07
0.07

Olfr889
0.02
0.04
0.03
0.04
0.05
0.03
0.05
0.10

Olfr890
0.04
0.05
0.04
0.04
0.03
0.06
0.07
0.08

Olfr891
0.07
0.10
0.09
0.11
0.11
0.09
0.10
0.15

Olfr893
0.06
0.05
0.04
0.06
0.05
0.07
0.06
0.09

Olfr894
0.05
0.07
0.04
0.05
0.06
0.07
0.06
0.09

Olfr895
0.01
0.02
0.02
0.06
0.07
0.03
0.05
0.08

Olfr898
0.14
0.20
0.19
0.21
0.18
0.21
0.21
0.17

Olfr899
0.11
0.15
0.13
0.14
0.14
0.17
0.16
0.14

Olfr9
0.09
0.12
0.14
0.14
0.14
0.14
0.11
0.14

Olfr90
0.15
0.20
0.19
0.23
0.19
0.23
0.20
0.25

Olfr900
0.11
0.15
0.12
0.16
0.15
0.16
0.13
0.12

Olfr901
0.16
0.18
0.19
0.26
0.20
0.22
0.19
0.23

Olfr902
0.13
0.14
0.15
0.17
0.17
0.21
0.19
0.22

Olfr904
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.08

Olfr905
0.01
0.05
0.05
0.07
0.04
0.05
0.08
0.10

Olfr906
0.06
0.11
0.10
0.09
0.09
0.11
0.11
0.13

Olfr907
0.07
0.07
0.07
0.10
0.09
0.10
0.09
0.09

Olfr908
0.06
0.12
0.07
0.10
0.12
0.11
0.09
0.13

Olfr91
0.40
0.47
0.41
0.46
0.46
0.47
0.43
0.50

Olfr910
0.00
0.02
0.01
0.06
0.02
0.03
0.02
0.03

Olfr911-ps1
0.04
0.05
0.04
0.05
0.05
0.04
0.06
0.10

Olfr912
0.02
0.02
0.03
0.03
0.06
0.03
0.05
0.07

Olfr913
0.06
0.11
0.08
0.09
0.09
0.09
0.10
0.14

Olfr914
0.11
0.12
0.14
0.15
0.14
0.15
0.16
0.19

Olfr915
0.10
0.13
0.13
0.14
0.14
0.12
0.12
0.16

Olfr916
0.03
0.08
0.05
0.06
0.05
0.06
0.05
0.07

Olfr917
0.12
0.16
0.11
0.16
0.16
0.15
0.14
0.13

Olfr918
0.07
0.09
0.08
0.09
0.08
0.09
0.09
0.15

Olfr919
0.15
0.23
0.20
0.21
0.20
0.25
0.22
0.24

Olfr92
0.24
0.35
0.28
0.37
0.33
0.35
0.31
0.32

Olfr920
0.30
0.27
0.34
0.29
0.21
0.21
0.29
0.26

Olfr921
0.04
0.07
0.05
0.06
0.08
0.05
0.08
0.09

Olfr922
0.17
0.16
0.16
0.19
0.16
0.19
0.20
0.17

Olfr923
0.15
0.16
0.16
0.19
0.16
0.17
0.17
0.21

Olfr924
NA
NA
0.01
NA
0.00
0.00
0.04
0.01

Olfr926
NA
0.01
0.01
0.02
0.04
0.03
0.03
0.09

Olfr93
0.20
0.26
0.21
0.28
0.24
0.26
0.20
0.22

Olfr930
0.06
0.09
0.07
0.09
0.08
0.11
0.08
0.11

Olfr933
0.14
0.18
0.17
0.17
0.19
0.19
0.20
0.23

Olfr934
0.06
0.09
0.07
0.08
0.10
0.09
0.11
0.11

Olfr935
0.10
0.11
0.11
0.13
0.12
0.11
0.15
0.17

Olfr936
NA
0.02
0.01
0.01
0.02
NA
0.01
0.05

Olfr937
0.06
0.07
0.06
0.07
0.08
0.10
0.07
0.09

Olfr938
0.09
0.13
0.12
0.10
0.13
0.16
0.12
0.14

Olfr94
0.24
0.26
0.24
0.28
0.29
0.26
0.27
0.26

Olfr943
0.04
0.07
0.05
0.07
0.05
0.08
0.07
0.08

Olfr944
0.02
0.06
0.04
0.06
0.05
0.05
0.04
0.06

Olfr945
0.03
0.03
0.03
0.02
0.04
0.05
0.03
0.05

Olfr947-ps1
0.05
0.07
0.06
0.06
0.06
0.09
0.07
0.10

Olfr948
NA
0.00
0.01
0.04
0.04
NA
0.01
0.08

Olfr95
0.31
0.34
0.31
0.40
0.38
0.40
0.37
0.35

Olfr951
0.07
0.09
0.07
0.10
0.08
0.10
0.08
0.10

Olfr952
0.02
0.03
0.02
0.03
0.03
0.04
0.03
0.06

Olfr954
0.07
0.09
0.07
0.10
0.08
0.10
0.08
0.10

Olfr955
0.08
0.09
0.09
0.11
0.09
0.12
0.11
0.15

Olfr957
0.10
0.13
0.09
0.11
0.13
0.12
0.11
0.13

Olfr958
0.23
0.23
0.24
0.26
0.23
0.27
0.25
0.23

Olfr959
0.23
0.28
0.25
0.27
0.28
0.27
0.26
0.26

Olfr96
0.22
0.28
0.23
0.28
0.26
0.29
0.24
0.27

Olfr960
0.12
0.12
0.10
0.16
0.13
0.16
0.16
0.17

Olfr961
0.06
0.10
0.06
0.09
0.09
0.10
0.10
0.15

Olfr963
0.13
0.11
0.15
0.13
0.14
0.12
0.09
0.08

Olfr965
0.13
0.14
0.15
0.16
0.13
0.17
0.13
0.17

Olfr967
0.14
0.16
0.14
0.17
0.16
0.17
0.14
0.17

Olfr968
0.00
0.03
0.03
0.01
0.00
0.03
0.03
0.05

Olfr969
0.03
0.05
0.05
0.08
0.08
0.07
0.05
0.08

Olfr97
0.06
0.17
0.09
0.15
0.12
0.10
0.11
0.15

Olfr970
0.01
0.05
0.02
0.05
0.06
0.05
0.04
0.06

Olfr971
0.08
0.11
0.08
0.09
0.10
0.10
0.10
0.09

Olfr972
0.03
0.05
0.05
0.08
0.07
0.04
0.08
0.07

Olfr974
0.23
0.27
0.24
0.30
0.30
0.28
0.28
0.29

Olfr975
0.27
0.31
0.30
0.32
0.32
0.32
0.31
0.33

Olfr976
0.16
0.19
0.18
0.21
0.19
0.23
0.21
0.25

Olfr978
0.24
0.29
0.26
0.30
0.32
0.28
0.26
0.27

Olfr979
0.17
0.22
0.18
0.21
0.20
0.21
0.20
0.23

Olfr98
0.06
0.17
0.09
0.15
0.12
0.10
0.11
0.15

Olfr980
0.16
0.19
0.20
0.21
0.22
0.23
0.21
0.23

Olfr981
0.22
0.25
0.23
0.26
0.30
0.25
0.23
0.28

Olfr982
0.35
0.41
0.34
0.42
0.42
0.45
0.37
0.44

Olfr983
0.03
0.06
0.03
0.06
0.07
0.05
0.04
0.06

Olfr984
0.29
0.33
0.32
0.36
0.34
0.37
0.36
0.35

Olfr985
0.16
0.20
0.18
0.22
0.19
0.25
0.21
0.21

Olfr986
0.19
0.21
0.19
0.22
0.23
0.22
0.20
0.27

Olfr987
0.06
0.08
0.10
0.11
0.08
0.11
0.10
0.08

Olfr988
0.10
0.12
0.12
0.14
0.13
0.13
0.12
0.16

Olfr99
0.14
0.31
0.19
0.34
0.25
0.30
0.30
0.30

Olfr992
0.08
0.11
0.11
0.11
0.11
0.16
0.17
0.13

Olfr993
0.02
0.05
0.03
0.11
0.05
0.06
0.06
0.11

Olfr994
0.06
0.06
0.05
0.08
0.08
0.07
0.04
0.14

Olfr995
0.01
0.02
0.02
0.03
0.04
0.04
0.02
0.09

Olfr996
0.04
0.03
0.05
0.05
0.04
0.04
0.07
0.13

Olfr998
0.17
0.20
0.19
0.21
0.19
0.19
0.19
0.22

TABLE 2

Olfactory receptors and accessory genes expression in sorted vascular macrophages from Apoe −/− mice in

western diet

RPKM value

RPKM value

RPKM value

Gene name
Cut-off 0.05
Gene name
Cut-off 0.05
Gene name
Cut-off 0.05

Rtp1
0.112
Olfr108
0.09
Olfr118
0.05

Rtp2
0.106
Olfr1082
0.15
Olfr1180
0.05

Reep3
11.44
Olfr1085
0.17
Olfr1183
0.07

Cngal
0.106
Olfr1086
0.06
Olfr1188
0.08

Cnga2
0.12
Olfr109
0.09
Olfr1189
0.05

Cnga3
0.147
Olfr1090
0.47
Olfr119
0.05

Cnga4
0.157
Olfr1094
0.08
Olfr1193
0.07

Cngb1
0.283
Olfr1095
0.08
Olfr1195
0.11

Acy3
0.862
Olfr110
0.27
Olfr1196
0.05

Gnal
1.513
Olfr1102
0.05
Olfr1199
0.05

Olfr1
0.09
Olfr1104
0.11
Olfr12
0.36

Olfr10
0.08
Olfr1107
0.06
Olfr1200
0.09

Olfr1000
0.23
Olfr1109
0.19
Olfr1201
0.19

Olfr1006
0.09
Olfr111
0.26
Olfr1202
0.05

Olfr1009
0.08
Olfr1112
0.60
Olfr1204
0.05

Olfr101
0.10
Olfr1120
0.09
Olfr1205
0.05

Olfr1010
0.28
Olfr1121
0.11
Olfr1206
0.14

Olfr1012
0.07
Olfr1122
0.21
Olfr1208
0.07

Olfr1014
0.09
Olfr1124
0.30
Olfr1211
0.07

Olfr1015
0.05
Olfr1128
0.05
Olfr1213
0.10

Olfr1016
0.37
Olfr1131
0.05
Olfr1214
0.07

Olfr1019
0.06
Olfr1132
0.11
Olfr1215
0.09

Olfr1020
0.08
Olfr1133
0.11
Olfr1216
0.07

Olfr1022
0.07
Olfr1134
0.05
Olfr1218
0.11

Olfr1023
0.10
Olfr1135
0.08
Olfr122
0.09

Olfr1026
0.12
Olfr1137
0.07
Olfr1221
0.10

Olfr1029
0.06
Olfr1138
0.11
Olfr1222
0.05

Olfr103
0.06
Olfr1143
0.09
Olfr1223
0.07

Olfr1030
0.28
Olfr1145
0.23
Olfr1226
0.07

Olfr1031
0.05
Olfr1148
0.11
Olfr1228
0.05

Olfr1032
0.06
Olfr115
0.16
Olfr123
0.50

Olfr1033
3.64
Olfr1152
0.23
Olfr1230
0.06

Olfr1037
0.07
Olfr1156
0.09
Olfr1231
0.09

Olfr1042
0.10
Olfr1157
0.06
Olfr1233
0.07

Olfr1043
0.08
Olfr1161
0.12
Olfr1238
0.11

Olfr1044
0.06
Olfr1162
0.06
Olfr124
0.05

Olfr1046
0.09
Olfr1163
0.05
Olfr1240
0.09

Olfr1047
0.08
Olfr1166
0.09
Olfr1243
0.06

Olfr1048
0.05
Olfr1167
0.08
Olfr1245
0.06

Olfr1055
0.05
Olfr1168
0.11
Olfr1246
0.08

Olfr1056
0.06
Olfr117
0.12
Olfr1248
0.05

Olfr1065
0.07
Olfr1173
0.05
Olfr125
0.05

Olfr1066
0.08
Olfr1176
0.05
Olfr1251
0.05

Olfr1076
0.06
Olfr1178
0.15
Olfr1253
0.06

Olfr1079
0.11
Olfr1179
0.09
Olfr1255
0.07

Olfr1256
0.06
Olfr134
0.08
Olfr1412
0.20

Olfr1257
0.07
Olfr1340
0.07
Olfr1413
0.23

Olfr1258
0.15
Olfr1341
0.17
Olfr1414
0.52

Olfr1259
0.09
Olfr1342
0.09
Olfr1415
0.06

Olfr126
0.12
Olfr1344
0.45
Olfr1416
0.10

Olfr1260
0.06
Olfr1346
0.10
Olfr1417
0.21

Olfr1261
0.07
Olfr1347
0.10
Olfr1419
0.19

Olfr1262
0.05
Olfr1348
0.15
Olfr142
0.13

Olfr1264
0.13
Olfr1349
0.17
Olfr1420
0.98

Olfr1265
0.06
Olfr1350
0.19
Olfr1424
0.08

Olfr1269
0.25
Olfr1351
0.12
Olfr1426
0.06

Olfr1270
0.07
Olfr1353
0.05
Olfr1427
0.09

Olfr1271
0.05
Olfr1355
0.08
Olfr1428
0.15

Olfr1272
0.05
Olfr1356
0.40
Olfr143
0.08

Olfr1273-ps
0.06
Olfr1357
0.15
Olfr1431
0.13

Olfr1275
0.08
Olfr1361
0.19
Olfr1437
0.10

Olfr1278
0.06
Olfr1362
0.05
Olfr1440
0.14

Olfr128
0.09
Olfr1364
0.06
Olfr1441
0.06

Olfr1282
0.05
Olfr1366
0.13
Olfr1442
0.08

Olfr1284
0.13
Olfr1367
0.06
Olfr1443
0.05

Olfr1289
0.06
Olfr137
0.08
Olfr1444
0.16

Olfr129
0.07
Olfr1370
0.06
Olfr1445
0.09

Olfr1290
0.07
Olfr1372-ps1
0.10
Olfr1446
0.14

Olfr1299
0.08
Olfr1377
0.07
Olfr1447
0.06

Olfr13
0.09
Olfr1378
0.22
Olfr1448
0.09

Olfr1300-ps1
0.07
Olfr138
0.07
Olfr1449
0.15

Olfr1302
0.06
Olfr1380
0.05
Olfr145
0.07

Olfr1303
0.15
Olfr1382
0.10
Olfr1450
0.17

Olfr1305
0.07
Olfr1384
0.08
Olfr1451
0.05

Olfr1309
0.11
Olfr1385
0.09
Olfr1454
0.05

Olfr131
0.11
Olfr1386
0.05
Olfr1461
0.05

Olfr1311
0.05
Olfr1387
0.12
Olfr1462
0.08

Olfr1312
0.06
Olfr1388
0.12
Olfr1463
0.05

Olfr1313
0.05
Olfr1389
0.32
Olfr1465
0.07

Olfr1316
0.05
Olfr139
0.13
Olfr1469
0.17

Olfr1318
0.09
Olfr1390
0.13
Olfr147
0.09

Olfr132
0.11
Olfr1391
0.08
Olfr149
0.20

Olfr1321
0.07
Olfr1392
0.17
Olfr1490
0.12

Olfr1322
0.22
Olfr1393
0.12
Olfr1491
0.06

Olfr1328
0.10
Olfr1394
0.19
Olfr1494
0.10

Olfr1329
0.05
Olfr1395
0.17
Olfr1495
0.11

Olfr133
0.10
Olfr1396
0.13
Olfr1496
0.11

Olfr1330
0.25
Olfr140
0.09
Olfr15
0.19

Olfr1331
0.33
Olfr1402
0.13
Olfr150
0.10

Olfr1335
0.11
Olfr1404
0.14
Olfr1500
0.27

Olfr1336
0.15
Olfr1406
0.24
Olfr1501
0.21

Olfr1337
0.17
Olfr1408
0.17
Olfr1504
0.05

Olfr1338
0.23
Olfr1410
0.16
Olfr1505
0.12

Olfr1339
0.16
Olfr1411
0.19
Olfr1507
0.24

Olfr1508
0.07
Olfr24
0.07
Olfr330
0.12

Olfr151
0.08
Olfr248
0.05
Olfr332
0.15

Olfr1511
0.06
Olfr25
0.05
Olfr338
0.06

Olfr1512
0.09
Olfr259
0.06
Olfr339
0.06

Olfr1513
0.09
Olfr26
0.12
Olfr341
0.14

Olfr153
0.05
Olfr262
0.09
Olfr342
0.07

Olfr1535
0.09
Olfr263
0.11
Olfr344
0.06

Olfr155
0.13
Olfr266
0.05
Olfr345
0.06

Olfr156
0.17
Olfr267
0.11
Olfr346
0.11

Olfr157
0.26
Olfr272
0.11
Olfr347
0.06

Olfr159
0.16
Olfr273
0.09
Olfr350
0.18

Olfr160
0.07
Olfr279
0.20
Olfr351
0.10

Olfr161
0.15
Olfr281
0.32
Olfr352
0.12

Olfr164
0.06
Olfr282
0.24
Olfr353
0.12

Olfr165
0.08
Olfr283
0.08
Olfr354
0.13

Olfr166
0.08
Olfr284
0.16
Olfr356
0.07

Olfr167
0.09
Olfr286
0.20
Olfr357
0.08

Olfr169
0.06
Olfr287
0.11
Olfr358
0.19

Olfr17
0.46
Olfr288
0.09
Olfr360
0.06

Olfr170
0.08
Olfr29-ps1
0.10
Olfr361
0.14

Olfr172
0.08
Olfr291
0.06
Olfr362
0.09

Olfr175-ps1
0.06
Olfr294
0.06
Olfr365
0.12

Olfr179
0.15
Olfr295
0.05
Olfr366
0.20

Olfr18
0.08
Olfr299
0.07
Olfr368
0.12

Olfr187
0.09
Olfr3
0.19
Olfr370
0.16

Olfr19
0.05
Olfr30
0.25
Olfr371
0.12

Olfr190
0.05
Olfr301
0.06
Olfr372
0.14

Olfr191
0.08
Olfr303
0.11
Olfr373
0.15

Olfr196
0.13
Olfr304
0.08
Olfr374
0.28

Olfr197
0.07
Olfr308
0.05
Olfr376
0.07

Olfr198
0.05
Olfr309
0.11
Olfr378
0.12

Olfr2
0.05
Olfr31
0.25
Olfr382
0.06

Olfr202
0.11
Olfr310
0.10
Olfr384
0.05

Olfr211
0.22
Olfr311
0.13
Olfr389
0.05

Olfr212
0.13
Olfr312
0.05
Olfr39
0.88

Olfr213
0.08
Olfr313
0.13
Olfr390
0.11

Olfr214
0.10
Olfr314
0.20
Olfr393
0.05

Olfr215
0.10
Olfr315
0.22
Olfr394
0.07

Olfr218
0.11
Olfr316
0.16
Olfr395
0.10

Olfr220
0.14
Olfr317
0.15
Olfr397
0.09

Olfr221
0.15
Olfr318
0.11
Olfr398
0.17

Olfr222
0.36
Olfr319
0.12
Olfr399
0.14

Olfr223
0.21
Olfr32
0.10
Olfr401
0.05

Olfr224
0.19
Olfr320
0.14
Olfr406-ps
0.12

Olfr225
0.12
Olfr323
0.12
Olfr411
0.21

Olfr229
0.33
Olfr324
0.10
Olfr412
0.11

Olfr23
0.64
Olfr328
0.12
Olfr414
0.08

Olfr237-ps1
0.11
Olfr329-ps
0.06
Olfr417
0.05

Olfr239
0.06
Olfr33
0.06
Olfr418-ps1
0.23

Olfr419
0.05
Olfr498
0.20
Olfr566
0.10

Olfr424
0.24
Olfr5
0.28
Olfr568
0.07

Olfr43
0.21
Olfr50
0.48
Olfr57
0.19

Olfr432
0.37
Olfr506
0.16
Olfr571
0.14

Olfr433
0.61
Olfr507
0.14
Olfr572
0.08

Olfr434
0.05
Olfr508
0.17
Olfr575
0.05

Olfr435
0.05
Olfr509
0.09
Olfr576
0.08

Olfr437
0.11
Olfr51
0.12
Olfr577
0.16

Olfr444
0.12
Olfr510
0.15
Olfr578
0.13

Olfr446
0.14
Olfr512
0.12
Olfr58
0.08

Olfr447
0.08
Olfr513
0.14
Olfr582
0.10

Olfr448
0.10
Olfr514
0.09
Olfr584
0.09

Olfr449
0.09
Olfr517
0.14
Olfr585
0.09

Olfr450
0.09
Olfr52
0.07
Olfr589
0.09

Olfr452
0.15
Olfr520
0.11
Olfr59
0.18

Olfr453
0.07
Olfr521
0.09
Olfr592
0.07

Olfr455
0.26
Olfr522
0.15
Olfr593
0.05

Olfr456
0.42
Olfr523
0.19
Olfr594
0.06

Olfr457
0.11
Olfr524
0.15
Olfr598
0.05

Olfr458
0.16
Olfr525
0.08
Olfr6
0.08

Olfr46
0.13
Olfr527
0.15
Olfr60
0.45

Olfr460
0.10
Olfr53
0.10
Olfr600
0.09

Olfr461
0.08
Olfr530
0.12
Olfr601
0.09

Olfr462
0.10
Olfr531
0.05
Olfr603
0.06

Olfr463
0.06
Olfr532
0.11
Olfr605
0.07

Olfr464
0.14
Olfr533
0.11
Olfr606
0.06

Olfr466
0.09
Olfr535
0.25
Olfr608
0.06

Olfr467
0.13
Olfr536
0.09
Olfr609
0.14

Olfr47
0.09
Olfr538
0.14
Olfr61
0.09

Olfr470
0.18
Olfr539
0.09
Olfr610
0.07

Olfr472
0.08
Olfr54
0.19
Olfr612
0.05

Olfr473
0.18
Olfr541
0.10
Olfr613
30.74

Olfr479
0.12
Olfr543
0.54
Olfr615
0.19

Olfr48
0.07
Olfr544
0.07
Olfr617
0.17

Olfr480
0.08
Olfr545
0.16
Olfr619
0.05

Olfr481
0.10
Olfr547
0.19
Olfr62
0.15

Olfr482
0.09
Olfr549
0.24
Olfr622
0.05

Olfr483
0.08
Olfr550
0.15
Olfr623
0.05

Olfr484
0.11
Olfr551
0.34
Olfr624
0.05

Olfr485
0.26
Olfr552
0.09
Olfr629
0.08

Olfr486
0.10
Olfr553
0.05
Olfr63
0.06

Olfr487
0.06
Olfr554
0.63
Olfr630
0.05

Olfr49
0.08
Olfr555
0.09
Olfr631
0.07

Olfr490
0.05
Olfr556
0.18
Olfr632
0.26

Olfr491
0.07
Olfr557
0.05
Olfr633
0.12

Olfr493
0.08
Olfr558
0.09
Olfr635
0.10

Olfr494
0.09
Olfr559
0.17
Olfr638
0.09

Olfr495
0.08
Olfr56
0.20
Olfr639
0.15

Olfr497
0.13
Olfr561
0.15
Olfr64
0.06

Olfr640
0.18
Olfr703
0.15
Olfr801
0.22

Olfr641
0.11
Olfr704
0.11
Olfr802
0.14

Olfr642
0.11
Olfr705
0.17
Olfr803
0.05

Olfr643
0.05
Olfr706
0.19
Olfr806
0.06

Olfr644
0.06
Olfr71
0.20
Olfr808
0.22

Olfr645
0.20
Olfr710
0.31
Olfr810
0.07

Olfr646
0.18
Olfr711
0.10
Olfr812
0.05

Olfr648
0.24
Olfr714
0.17
Olfr814
0.16

Olfr649
0.09
Olfr715
0.07
Olfr816
0.43

Olfr65
0.07
Olfr716
0.11
Olfr818
0.08

Olfr651
0.16
Olfr720
0.23
Olfr822
0.10

Olfr652
0.10
Olfr73
0.11
Olfr827
0.06

Olfr653
0.19
Olfr731
0.10
Olfr829
0.07

Olfr655
0.09
Olfr733
0.05
Olfr832
0.09

Olfr656
0.05
Olfr734
0.11
Olfr834
0.06

Olfr658
0.06
Olfr735
0.08
Olfr835
0.13

Olfr659
0.14
Olfr736
0.12
Olfr836
0.17

Olfr66
0.10
Olfr738
0.26
Olfr843
0.07

Olfr661
0.08
Olfr739
0.07
Olfr854
0.11

Olfr663
0.06
Olfr74
0.11
Olfr856-ps1
79.03

Olfr665
0.07
Olfr740
0.12
Olfr857
0.23

Olfr666
0.12
Olfr741
0.08
Olfr860
0.14

Olfr667
0.05
Olfr742
0.06
Olfr866
0.06

Olfr668
0.10
Olfr744
0.08
Olfr869
0.06

Olfr669
0.44
Olfr745
0.60
Olfr871
0.05

Olfr67
0.05
Olfr747
0.09
Olfr874
0.06

Olfr670
0.08
Olfr748
0.05
Olfr875
0.12

Olfr672
0.08
Olfr749
0.08
Olfr876
0.07

Olfr676
0.44
Olfr75-ps1
0.16
Olfr877
0.12

Olfr678
0.07
Olfr750
0.21
Olfr878
0.09

Olfr683
0.05
Olfr76
0.10
Olfr881
0.15

Olfr684
0.07
Olfr763
0.13
Olfr883
0.12

Olfr685
0.20
Olfr765
0.05
Olfr884
0.06

Olfr686
0.13
Olfr767
0.07
Olfr885
0.14

Olfr688
0.15
Olfr768
0.06
Olfr887
0.06

Olfr689
0.09
Olfr769
0.05
Olfr888
0.14

Olfr690
0.06
Olfr770
0.07
Olfr891
0.06

Olfr691
0.21
Olfr772
0.06
Olfr893
0.14

Olfr692
0.18
Olfr773
0.06
Olfr894
0.05

Olfr693
0.09
Olfr777
0.05
Olfr9
0.17

Olfr694
0.08
Olfr78
0.05
Olfr90
0.10

Olfr695
0.26
Olfr782
0.05
Olfr904
0.08

Olfr697
0.06
Olfr784
0.11
Olfr905
0.09

Olfr698
0.23
Olfr786
0.15
Olfr906
0.22

Olfr699
0.07
Olfr790
0.18
Olfr907
0.09

Olfr70
0.18
Olfr791
0.12
Olfr91
0.12

Olfr700
0.32
Olfr794
0.09
Olfr911-ps1
0.17

Olfr701
0.08
Olfr796
0.12
Olfr876
0.07

Olfr702
0.10
Olfr800
0.09
Olfr877
0.12

Olfr917
0.05
Olfr914
0.09
Olfr878
0.09

Olfr92
0.19
Olfr916
0.08
Olfr881
0.15

Olfr922
0.06
Olfr917
0.05
Olfr883
0.12

Olfr923
0.17
Olfr92
0.19
Olfr884
0.06

Olfr803
0.05
Olfr922
0.06
Olfr885
0.14

Olfr806
0.06
Olfr923
0.17
Olfr887
0.06

Olfr808
0.22
Olfr924
0.05
Olfr888
0.14

Olfr810
0.07
Olfr926
0.05
Olfr891
0.06

Olfr812
0.05
Olfr930
0.06
Olfr893
0.14

Olfr814
0.16
Olfr934
0.12
Olfr894
0.05

Olfr816
0.43
Olfr935
0.05
Olfr9
0.17

Olfr818
0.08
Olfr937
0.07
Olfr90
0.10

Olfr822
0.10
Olfr94
0.15
Olfr904
0.08

Olfr827
0.06
Olfr945
0.08
Olfr905
0.09

Olfr829
0.07
Olfr948
0.05
Olfr906
0.22

Olfr832
0.09
Olfr95
0.20
Olfr907
0.09

Olfr834
0.06
Olfr951
0.11
Olfr91
0.12

Olfr835
0.13
Olfr952
0.06
Olfr911-ps1
0.17

Olfr836
0.17
Olfr957
0.10
Olfr979
0.15

Olfr843
0.07
Olfr958
0.21
Olfr98
0.19

Olfr854
0.11
Olfr959
0.13
Olfr981
0.07

Olfr856-ps1
79.03
Olfr961
0.05
Olfr982
0.10

Olfr857
0.23
Olfr963
0.07
Olfr983
0.14

Olfr860
0.14
Olfr967
0.08
Olfr984
0.07

Olfr866
0.06
Olfr969
0.06
Olfr986
0.13

Olfr869
0.06
Olfr97
0.07
Olfr988
0.05

Olfr871
0.05
Olfr971
0.12
Olfr99
0.32

Olfr874
0.06
Olfr974
0.06
Olfr996
0.08

Olfr875
0.12
Olfr975
0.12
Olfr998
0.06

TABLE 3

Olfrs expressed in vascular macrophages in mice, along with corresponding human ortholog

Mouse
Human orth.
Mouse
Human orth.
Mouse
Human orth.
Mouse
Human orth.

Olfr239
OR10H1
Olfr1461
OR5B3
Olfr694
OR2AG1, OR2AG2
Olfr1022
OR5M1, OR5M10

Olfr1174-ps
AP006437.1
Olfr874
OR8B12
Olfr1028
OR5M11
Olfr1138
OR5W2

Olfr401
OR3A1
Olfr406
OR1P1
Olfr469
OR5P2
Olfr470
OR5P2

Olfr91
OR2H1, OR2H2
Olfr638
OR51Q1
Olfr486
OR5P2
Olfr1219
OR4C15

Olfr1029
OR5M11
Olfr460
OR9A4
Olfr487
OR5P2
Olfr430
OR6N2, OR2A42

Olfr314
OR2T12
Olfr1222
OR4C15
Olfr376
OR1E1
Olfr1038-ps
OR5R1, OR8J3

Olfr320
OR2AK2, OR2T4,
Olfr692
OR52W1, OR2AG2
Olfr720
OR2T6
Olfr1356
OR7C2, OR2J2,

OR2T5

OR2J3

Olfr566
OR51F1
Olfr441
OR2A14
Olfr574
OR51T1
Olfr77
OR7D4

Olfr55
OR10H1, OR52K2
Olfr447
OR2A25
Olfr1423
OR4D11
Olfr715
OR2D2

Olfr1510
OR10G2
Olfr362
OR1B1, ORIL6
Olfr248
OR10X1
Olfr1211
OR4C15

Olfr316
OR2AK2
Olfr1016
OR9G1, OR12D2
Olfr1104
OR8I2
Olfr218
OR10J3

Olfr92
OR2H1, OR2H2
Olfr419
OR10Z1
Olfr1032
OR5M3
Olfr57
OR7A10

Olfr982
OR10S1
Olfr76
OR5A1
Olfr1136
OR5W2
Olfr495
OR5P2

Olfr398
AC087498.1
Olfr1491
OR10Q1
Olfr1264
OR4C3
Olfr808
OR6C65

Olfr522
OR6Q1, OR10H2,
Olfr96
OR11A1, OR10G7,
Olfr518
OR10A3, OR10A6
Olfr1352
OR7A10, OR7A17,

OR10H5

OR10G8

OR7A5

Olfr147
OR8B2
Olfr211
OR13A1
Olfr519
OR10A3
Olfr393
OR1E1

Olfr678
OR52E5
Olfr986
OR6X1
Olfr835
OR7G2
Olfr631
OR51M1

Olfr1388
OR2Y1
Olfr1506
OR4X2
Olfr420
OR6K2
Olfr1202
OR4C13

Olfr1426
OR4D10
Olfr90
OR2H1, OR2H2
Olfr556
OR52I1
Olfr1097
OR8H2, OR8H3

Olfr169
OR2AJ1
Olfr167
OR2L2
Olfr1193
OR4S2
Olfr802
OR6C1

Olfr170
OR2AJ1
Olfr288
OR10AD1
Olfr1353
OR7A10, OR7A17,
Olfr1241
OR4A16, OR4A5,

OR7A5

OR4A8

Olfr171
OR2AJ1, OR5H14,
Olfr1495
OR10Q1
Olfr410
OR3A1
Olfr292
OR14C36

OR5H15

Olfr370
OR10K2, OR1E2,
Olfr1226
OR4C15
Olfr1255
OR4C12
Olfr677
OR52E4

OR1E1

Olfr267
OR2K2
Olfr558
OR51E1
Olfr1258
OR4C46
Olfr1270
OR4B1

Olfr796
OR10P1, OR7A17,
Olfr448
OR2A5
Olfr1166
OR5D13
Olfr1436
OR5AN1

OR7A5

Olfr63
OR10H3
Olfr1217
OR4C15
Olfr309
OR13G1
Olfr746
OR11H7

Olfr328
OR2T29, OR2DT4,
Olfr1490
OR10W1
Olfr659
OR52N4
Olfr384
OR1E1, OR1E2

OR2T5

Olfr1272
OR4B1
Olfr446
OR2A12
Olfr389
OR1E1
Olfr821
OR6C74

Olfr417
OR10X1
Olfr850
OR7G2
Olfr1057
OR8J1
Olfr937
OR8G1

Olfr485
OR5P2
Olfr641
OR51I2
Olfr979
OR10G4
Olfr836
OR7G2

Olfr222
OR2B11
Olfr137
OR2J1
Olfr1507
OR4E1
Olfr592
OR52J3, OR10H4

Olfr582
OR52R1
Olfr571
ORS1S1
Olfr262
OR5AN1
Olfr1289
OR4F17, OR2A7

Olfr1502
OR9I1
Olfr3
OR1J1
Olfr1387
OR2Y1
Olfr828
OR7G2

Olfr464
OR4D1
Olfr437
OR2A2
Olfr492
OR5P2
Olfr1023
OR5M1

Olfr1260
OR4C5
Olfr1444
OR5B21
Olfr830
OR7G2
Olfr1220
OR4C15

Olfr13
OR2A4, OR4F21,
Olfr635
OR51Q1
Olfr1209
OR4C16
Olfr8
OR7A10

OR4F29

Olfr1511
OR10G2
Olfr1137
OR5W2
Olfr1242
OR4A16, OR4A5,
Olfr679
OR56A3

OR4A8

Olfr95
OR10C1
Olfr102
OR12D1
Olfr168
OR2L13
Olfr681
OR56A3

Olfr750
OR6S1
Olfr1508
OR4E1
Olfr504
OR56B1
Olfr498
OR5P2

Olfr463
OR4D2
Olfr1238
OR4A16, OR4A5,
Olfr557
OR51D1
Olfr1170
OR5D13

OR4A8

Olfr231
OR6K6, OR10H2,
Olfr569
OR52R1, OR7A17,
Olfr1153
OR5W2
Olfr1243
OR4A16, OR4A5,

OR10H5

OR7A5

OR4A8

Olfr514
OR10A3, OR10A6
Olfr700
OR2AG1, OR2AG2
Olfr26
OR8D1
Olfr729
OR4K5

Olfr984
OR4D5
Olfr577
OR51G2
Olfr1431
OR5AN1
Olfr490
OR5P2

Olfr978
OR10G4, OR10G7,
Olfr706
OR2AG1, OR10A5
Olfr1263
OR4C45
Olfr1058
OR8K3

OR10G8

Olfr666
OR52N2, OR52E8
Olfr1259
OR4C12
Olfr876
OR8B12
Olfr1065
OR8K3

Olfr161
OR1F1, OR2L3,
Olfr1118
OR10AG1
Olfr382
OR1E1, OR1E2
Olfr1454
OR5B3

OR2L5

Olfr1076
OR8K3
Olfr981
OR10G6
Olfr873
OR7E24
Olfr1141
OR5W2

Olfr435
OR2A1
Olfr698
OR2AG1, OR2AG2
Olfr716
OR2D3
Olfr186
OR5H1, OR7A17,

OR7A5

Olfr745
OR11H6
Olfr875
OR8B12
Olfr1467
OR5B3
Olfr1014
OR9G1

Olfr402
OR3A1
Olfr1099
OR8H1
Olfr74
OR5D18
Olfr191
OR5H1, OR5H14,

OR5H15

Olfr788
OR6C3
Olfr1354
OR7A10, OR7A17,
Olfr142
OR4B1
Olfr378
OR1E2

OR7A5

Olfr723
OR4L1
Olfr1355
OR7A10
Olfr786
OR6C1
Olfr2
OR6A2

Olfr724
OR4L1
Olfr552
OR52K1
Olfr357
OR1Q1
Olfr1199
OR4C16

Olfr765
OR2AP1
Olfr790
OR6C75
Olfr640
OR51I1
Olfr1451
OR5B2

Olfr1428
OR4D6
Olfr867
OR7D4
Olfr930
OR8D1
Olfr512
OR10A3, OR10A6

Olfr39
OR7D4, OR1E2
Olfr494
OR5P2
Olfr68
OR52A5
Olfr1020
OR5AP2, OR5M10

Olfr329-ps
OR2T29, OR2T4,
Olfr19
OR7A10, OR5H14,
Olfr1249
OR4A16, OR4A5,
Olfr1273-ps
OR4B1, OR4F4,

OR2T5

OR5H15

OR4A8

OR4F5

Olfr331
OR2T29
Olfr688
OR56B4
Olfr1499
OR9I1
Olfr385
OR1E1, OR1E2

Olfr220
OR6Y1
Olfr985
OR8D4
Olfr497
OR5P2
Olfr295
OR14C36

Olfr459
OR9A2
Olfr354
OR1N2
Olfr1140
OR5W2
Olfr1228
OR4C15, OR4A5,

OR4A8

Olfr713
OR10A2
Olfr703
OR2AG1, OR2AG2
Olfr671
OR52E6
Olfr872
OR7E24

Olfr59
OR1P1
Olfr878
OR8B4, OR2H2
Olfr1303
OR4F16/17, OR7A5
Olfr944
OR8G1

Olfr145
OR8B8
Olfr697
OR2AG1, OR2AG2
Olfr1509
OR4E2
Olfr1116
OR10AG1

Olfr317
OR2W3
Olfr482
OR5P2
Olfr1469
OR5B3, OR8B3
Olfr936
OR8G5

Olfr689
OR56B4
Olfr506
OR5P2
Olfr466
OR9H1P
Olfr943
OR8G1

Olfr365
OR1L4
Olfr507
OR5P2, OR10A6
Olfr502
OR5P2
Olfr849
OR7G2

Olfr1252
OR4A16
Olfr520
OR2AT4
Olfr1466
OR5B3
Olfr1066
OR8K3

Olfr31
OR2T1, OR2T33,
Olfr554
OR52M1, OR52I2
Olfr1404
OR10J3
Olfr199
OR5AC1

OR2T8

Olfr958
OR10D3
Olfr484
OR5P2
Olfr32
OR4B1
Olfr1167
OR5D13

Olfr93
OR2H1
Olfr693
OR2AG1, OR2AG2
Olfr1442
OR5B3
Olfr196
OR5H1

TABLE 4

Human olfactory receptors expressed in coronaries

Gene
Controls NXT_A5
Case NXT_B5
GFOLD(0.01)
Gene_Name

ENSG00000181785.2
546.864638
578.635755
0
OR5AS1

ENSG00000176695.8
504.918616
563.419456
0
OR4F17

ENSG00000127530.3
386.176633
315.330905
−0.162011
OR7C1

ENSG00000204695.4
377.706822
556.177204
0.210455
OR14J1

ENSG00000228198.3
276.882578
318.614617
0
OR2M3

ENSG00000172146.2
276.518697
346.4817
0
OR1A1

ENSG00000183444.10
276.319502
433.805203
0.274878
OR7E38P

ENSG00000177201.2
254.799213
402.89834
0.270254
OR2T12

ENSG00000172519.9
214.260285
265.658244
0
OR10H5

ENSG00000203663.4
201.99031
291.13782
0.0984326
OR2L2

ENSG00000094661.3
181.6724
302.355662
0.299551
OR1I1

ENSG00000186723.4
169.65786
133.203895
−0.0897745
OR10H1

ENSG00000172742.5
162.285486
202.345304
0
OR4D9

ENSG00000254593.1
162.27436
84.3381327
−0.626424
OR7E126P

ENSG00000187847.4
159.507692
254.762033
0.218945
OR7E25P

ENSG00000255804.2
158.239868
112.673288
−0.188318
OR6J1

ENSG00000170356.9
139.080996
69.1550135
−0.640902
OR2A20P

ENSG00000173285.4
138A41653
167.502134
0
OR10K1

ENSG00000228336.2
136.812705
176.281207
0
OR9H1P

ENSG00000171561.4
133.862532
207.151682
0.140105
OR2AT4

ENSG00000172320.3
124.38252
173.357825
0
OR5A1

ENSG00000255303.2
122.229214
168.645339
0
OR5BA1P

ENSG00000184166.2
121.129162
132.773611
0
OR1D2

ENSG00000170790.5
120.097289
80.0655486
−0.232222
OR10A2

ENSG00000180785.9
110.761584
117.063217
0
OR51E1

ENSG00000188000.4
107.470536
136.721424
0
OR7D2

ENSG00000174667.4
105.063188
137.408601
0
OR7D4

ENSG00000170923.3
99.9626014
123.530422
0
OR7G2

ENSG00000284791.1
88.3624998
0
−3.74841
OR7E47P

ENSG00000183389.5
87.4286738
102.511116
0
OR56A4

ENSG00000274052.2
85.9523142
63.7066912
0
OR7E156P

ENSG00000215160.3
85.0764391
268.369648
1.12898
OR7E122P

ENSG00000188558.6
83.3979651
101.176283
0
OR2G6

ENSG00000203757.2
82.0528018
151.775593
0.314364
OR6K3

ENSG00000182070.5
76.7592432
131.555004
0.177862
OR52A1

ENSG00000232268.6
73.9029234
53.1062282
−0.017257
OR52I1

ENSG00000176495.3
73.3445318
8.15428516
−1.91019
OR5AN1

ENSG00000169208.2
72.063169
111.668453
0.00942992
OR10G3

ENSG00000221836.3
70.8155486
76.7516508
0
OR2A5

ENSG00000254737.2
69.2812575
162.790322
0.658625
OR10G4

ENSG00000185385.4
68.9845498
177.591567
0.789019
OR7A17

ENSG00000172324.5
68.9097609
71.4393367
0
OR5A2

ENSG00000197532.2
68.7974219
60.9833381
0
OR6Y1

ENSG00000229386.3
68.3171876
138.37922
0.422025
OR8B9P

ENSG00000249646.2
67.5546022
71.1007876
0
OR7E94P

ENSG00000176230.6
67.3145407
79.9467046
0
OR4K17

ENSG00000254752.2
65.1416483
71.0021782
0
OR5M2P

ENSG00000219926.11
64.8293406
3.86557323
−2.49098
OR7E104P

ENSG00000196119.7
63.3775606
53.0251179
0
OR8A1

ENSG00000180437.5
62.9029845
0
−3.2517
OR6K4P

ENSG00000168158.3
60.0437651
0
−3.18163
OR2C1

ENSG00000227892.1
60.0437207
0
−3.18163
OR5P4P

ENSG00000170929.6
59.4290287
92.9168677
0
OR1M1

ENSG00000169327.5
54.8306032
81.0759544
0
OR5AU1

ENSG00000226413.2
51.4660582
0
−2.9484
OR8T1P

ENSG00000205409.3
50.5129918
0
−2.9484
OR52E6

ENSG00000170683.6
49.5791167
67.8787387
0
OR10A3

ENSG00000196184.9
49.1793067
85.5376168
0.0905611
OR10J1

ENSG00000182652.3
48.8846845
6.12415162
−1.61798
OR4Q3

ENSG00000285474.1
47.6916295
0
−2.86146
OR7E154P

ENSG00000224402.2
45.8477711
63.8943019
0
OR6D1P

ENSG00000236032.3
45.1332562
68.0523365
0
OR5H14

ENSG00000180090.5
44.6279381
4.59413216
−1.66446
OR3A1

ENSG00000180934.6
44.2651434
72.6954164
0
OR56A1

ENSG00000272595.2
42.8095771
61.9533093
0
OR10AH1P

ENSG00000176253.3
42.0160431
69.7616334
0
OR4K13

ENSG00000159961.2
39.9535248
43.73905
0
OR3A3

ENSG00000243896.4
38.6890368
25.9453507
0
OR2A7

ENSG00000182613.2
37.6769509
58.8546337
0
OR2V2

ENSG00000171180.2
36.0617331
71.5995097
0.221662
OR2M4

ENSG00000167332.8
30.0670845
85.1835567
0.686353
OR51E2

ENSG00000179626.4
29.3418447
46.5122723
0
OR6C4

ENSG00000284689.1
28.6439911
12.5393039
−0.0918595
OR7E84P

ENSG00000177535.8
28.6215207
36.0929581
0
OR2B11

ENSG00000204700.5
28.3794383
40.6400862
0
OR2J2

ENSG00000221882.3
28.3044513
16.4305549
0
OR3A2

ENSG00000187857.4
28.2646054
54.1032411
0.042119
OR6C75

ENSG00000188269.9
27.7235813
31.5140557
0
OR7A5

ENSG00000196778.3
26.6804545
51.5584451
0.0208175
OR52K1

ENSG00000237258.8
26.5021368
32.452784
0
OR11A1

ENSG00000182854.8
26.4952553
40.14141
0
OR4F15

ENSG00000196534.5
24.9196619
33.5016257
0
OR9K1P

ENSG00000179615.2
24.3038141
41.804654
0
OR2AP1

ENSG00000224392.1
23.8268859
0
−1.8117
OR2G1P

ENSG00000197309.3
23.8268405
0
−1.8117
OR10D3

ENSG00000236359.1
21.9207231
0
−1.614
OR51B8P

ENSG00000188324.4
21.7452412
14.9005208
0
OR6C6

ENSG00000213215.5
21.0860876
46.3028088
0.189909
OR2F1

ENSG00000181693.8
20.8014812
11.6145091
0
OR8H1

ENSG00000167355.8
20.4650197
40.3322461
0.0112981
OR51B5

ENSG00000197125.3
20.0233414
9.80312258
0
OR8B8

ENSG00000181767.3
19.4605494
27.3553558
0
OR8H2

ENSG00000276240.2
19.2968745
8.23140684
0
OR4E1

ENSG00000180974.4
18.5520959
46.8234928
0.340268
OR52E4

ENSG00000181001.2
18.4750523
36.4094962
0
OR52N1

ENSG00000186513.3
18.1084257
0
−1.30024
OR9Q2

ENSG00000171496.4
18.0900614
9.22728509
0
OR1L8

ENSG00000177212.4
18.0687622
27.4919869
0
OR2T33

ENSG00000228307.2
17.9950181
12.3023386
0
OR2S1P

ENSG00000228960.6
17.9127332
8.88412332
0
OR2A9P

ENSG00000285405.1
17.8618733
0
−1.30024
OR11J6P

ENSG00000231861.2
17.1553819
0
−1.21004
OR5K2

ENSG00000197786.3
17.1553619
0
−1.21004
OR5B17

ENSG00000231548.2
16.1342986
24.5528768
0
OR55B1P

ENSG00000221933.3
16.0915447
83.5895442
1.42166
OR2A25

ENSG00000284768.1
15.8708554
0
−1.11392
OR2A12

ENSG00000197454.2
15.2810263
11.5155112
0
OR2L5

ENSG00000196242.9
15.0452579
12.2219147
0
OR2C3

ENSG00000196341.3
14.429841
13.1216065
0
OR8D1

ENSG00000196832.4
14.0244617
27.5769539
0
OR11G2

ENSG00000234485.5
13.6451259
1.89094436
−0.900453
OR7E46P

ENSG00000180658.4
13.4774257
4.35645584
0
OR2A4

ENSG00000176269.3
13.3430873
0
−0.780893
OR4F21

ENSG00000174957.1
13.3302961
8.15766182
0
OR5J2

ENSG00000197428.3
12.687851
23.1221105
0
OR51D1

ENSG00000188124.3
12.6658524
19.3691531
0
OR2AG2

ENSG00000186119.8
12.3899635
0
−0.65081
OR5D18

ENSG00000176798.2
11.8267594
20.955519
0
OR51L1

ENSG00000227152.6
11.4720377
16.2501062
0
OR2T7

ENSG00000177306.4
11.4603333
0
−0.508248
OR7E125P

ENSG00000184669.9
11.2959781
21.721789
0
OR7E14P

ENSG00000181927.3
10.9751701
32.4867146
0.127801
OR4P4

ENSG00000181518.4
10.7557213
35.1191278
0.286733
OR8D4

ENSG00000141194.6
10.5631057
15.2371567
0
OR4D1

ENSG00000244292.1
10.4837954
0
−0.350579
OR9N1P

ENSG00000273423.1
10.4319367
7.66719819
0
OR13I1P

ENSG00000176510.5
9.68307826
9.19509916
0
OR10AC1

ENSG00000205240.4
8.44623198
0
−0.008352
OR7E36P

ENSG00000233606.2
8.14883753
8.8199876
0
OR6C66P

ENSG00000237988.5
7.9657598
58.3501724
1.27572
OR2I1P

ENSG00000221888.4
7.80105605
3.0412225
0
OR1C1

ENSG00000279301.4
7.64688388
11.6049031
0
OR2T11

ENSG00000238243.3
7.62459069
0
−0.008352
OR2W3

ENSG00000254613.2
6.9527864
7.83296348
0
OR6M2P

ENSG00000187747.2
6.67155028
0
0
OR52B6

ENSG00000231049.2
6.53827785
7.00611683
0
OR52B5P

ENSG00000272937.2
5.81627334
17.507293
0
OR6U2P

ENSG00000166693.7
5.71844202
0
0
OR5M13P

ENSG00000181214.7
5.71843666
0
0
OR8G2P

ENSG00000254743.1
5.02054052
0
0
OR10V3P

ENSG00000258822.2
5.01359415
3.06027254
0
OR4K16P

ENSG00000167822.2
4.99342079
13.3152596
0
OR8J3

ENSG00000231237.1
4.90876873
5.2754809
0
OR6K1P

ENSG00000197849.6
4.8214225
6.09046705
0
OR8G1

ENSG00000182634.8
4.76544301
0
0
OR10G7

ENSG00000175398.2
4.76538558
0
0
OR10P1

ENSG00000198128.4
4.76529329
0
0
OR2L3

ENSG00000136834.3
4.50869629
11.5209323
0
OR1J1

ENSG00000267450.1
4.28362022
1.31368778
0
OR1AB1P

ENSG00000221970.2
4.21172164
6.36591094
0
OR2A1

ENSG00000180708.5
4.04281914
7.49534286
0
OR10K2

ENSG00000185372.3
3.86737836
9.5489069
0
OR2V1

ENSG00000237225.2
3.83277315
1.02230229
0
OR13K1P

ENSG00000236083.2
3.78692704
8.20484906
0
OR13E1P

ENSG00000273484.1
3.17139557
15.6655187
0.12071
OR6R2P

ENSG00000176231.2
3.05605359
0
0
OR10H4

ENSG00000221813.4
3.00184947
15.2722523
0.00301549
OR6B1

ENSG00000165762.3
2.9285894
8.15410454
0
OR4K2

ENSG00000251491.2
2.90325628
0
0
OR7E28P

ENSG00000279486.5
2.8894006
3.04534005
0
OR2AG1

ENSG00000231192.2
2.87103993
9.13098984
0
OR5H1

ENSG00000169488.6
2.85923931
0
0
OR4K15

ENSG00000282137.1
2.85923161
0
0
OR4G3P

ENSG00000255203.1
2.85922295
0
0
OR7E2P

ENSG00000183122.5
2.85921245
0
0
OR2A3P

ENSG00000259324.2
2.85920839
0
0
OR11K1P

ENSG00000189398.5
2.63024582
0
0
OR7E12P

ENSG00000254948.1
2.22885391
1.08803581
0
OR7E158P

ENSG00000235623.2
2.20667157
0
0
OR7E110P

ENSG00000184698.5
2.13789161
28.4812714
1.3736
OR51M1

ENSG00000250640.2
1.91942484
0
0
OR7E41P

ENSG00000204657.4
1.91137294
1.01858945
0
OR2H2

ENSG00000175619.3
1.90614891
0
0
OR4B1

ENSG00000172148.3
1.1695972
0
0
OR7A2P

ENSG00000250561.2
1.10800264
9.22895742
0.00835202
OR7E59P

ENSG00000285469.1
1.06276224
0
0
OR7E161P

ENSG00000279000.3
0.9668797
11.050567
0.350579
OR10A6

ENSG00000254472.1
0.96558353
5.02852014
0
OR4A49P

ENSG00000181074.4
0.96528631
28.167611
1.87204
OR52N4

ENSG00000186124.4
0.95922815
8.09787288
0
OR9M1P

ENSG00000221977.2
0.95848729
4.0756067
0
OR4E2

ENSG00000181718.6
0.95630535
4.06116094
0
OR5T2

ENSG00000186509.4
0.95620445
1.01540285
0
OR9Q1

ENSG00000242525.1
0.95430062
1.01824823
0
OR7E100P

ENSG00000176895.9
0.95308364
0
0
OR51A7

ENSG00000184140.6
0.95306147
0
0
OR4F6

ENSG00000225101.6
0.95302828
0
0
OR52K3P

ENSG00000183909.6
0
41.7949942
2.52693
OR4G2P

ENSG00000184022.4
0
37.6930047
2.36796
OR2T10

ENSG00000248553.1
0
36.6743329
2.32534
OR52H2P

ENSG00000238228.1
0
35.6555844
2.28142
OR7E7P

ENSG00000176904.3
0
30.5619742
2.03938
OR51H1

ENSG00000177174.1
0
27.5057615
1.87204
OR14C36

ENSG00000181780.4
0
27.5057426
1.87204
OR5J1P

ENSG00000249633.1
0
22.4120845
1.54166
OR52V1P

ENSG00000228914.2
0
18.3371754
1.21004
OR1H1P

ENSG00000237610.1
0
16.2997032
1.01105
OR4C50P

ENSG00000255030.1
0
14.2622616
0.780893
OR8B5P

ENSG00000205495.1
0
13.2435191
0.65081
OR52J3

ENSG00000231319.3
0
12.2247952
0.508248
OR2B3

ENSG00000244623.1
0
11.5834438
0.508248
OR2AE1

ENSG00000279270.2
0
11.2060429
0.350579
OR52R1

ENSG00000197882.3
0
10.4088558
0
OR7E13P

ENSG00000230655.3
0
9.36785945
0.00835202
OR7E55P

ENSG00000214344.4
0
9.17599513
0.00835202
OR4F13P

ENSG00000226288.2
0
9.16866232
0.00835202
OR52I2

ENSG00000203408.4
0
9.16859147
0.00835202
OR6C71P

ENSG00000184478.7
0
8.14976718
0
OR56A3

ENSG00000258550.1
0
7.7890611
0
OR7E106P

ENSG00000274360.2
0
7.13113873
0
OR6W1P

ENSG00000280094.2
0
7.13113737
0
OR1B1

ENSG00000204701.2
0
5.09376099
0
OR2J3

ENSG00000166884.2
0
5.09365521
0
OR4D6

ENSG00000228547.5
0
4.52426088
0
OR7E26P

ENSG00000230261.1
0
4.07491126
0
OR52J2P

ENSG00000197938.5
0
4.0749112
0
OR5H2

ENSG00000273252.1
0
3.1590137
0
OR7E39P

ENSG00000225980.4
0
3.06023742
0
OR7E19P

ENSG00000232511.4
0
3.05624557
0
OR2AH1P

ENSG00000232381.1
0
3.05620091
0
OR52U1P

ENSG00000254848.1
0
3.05619803
0
OR5BN1P

ENSG00000180409.3
0
3.05619094
0
OR10AA1P

ENSG00000181009.5
0
3.05615923
0
OR52N5

ENSG00000277932.2
0
3.05612603
0
OR52E5

ENSG00000226537.2
0
2.08221903
0
OR7E33P

ENSG00000171936.2
0
2.03745586
0
OR10H3

ENSG00000198601.3
0
1.01876029
0
OR2M2

ENSG00000174937.4
0
1.01875812
0
OR5M3

ENSG00000196099.4
0
1.01875546
0
OR6M1

ENSG00000172640.3
0
1.01875434
0
OR10AD1

ENSG00000189181.4
0
1.01871442
0
OR14I1

ENSG00000176951.6
0
1.01871387
0
OR51N1P

ENSG00000257542.5
17.7745506
0
−1.30024
OR7E47P

ENSG00000221858.3
0
22.0390932
1.54166
OR2A12

TABLE 5

Human olfactory receptors found in the Biobank of Karolinska

Endarterectomy (BiKE) dataset

OR5E1P
OR5AK4P
OR51M1
OR7E111P
OR1J2

OR2I1P
OR2AD1P
OR52A1
OR1F1
OR10D3

OR10A3
OR10C1
OR6W1P
OR51I2
OR2A20P

OR3A2
OR51E2
OR7A5
OR2C1
OR1D2

OR5G1P
OR2A4
OR7A17
OR7E47P
OR10A4

OR7E24
OR2L1P
OR4A1P
OR3A3
OR8B8

OR2H4P
OR6A2
OR10J1
OR1F2P
OR1Q1

OR2B4P
OR2F1
OR2S2
OR13C4
OR1A1

OR8G2
OR51E1
OR5L2
OR52K3P
OR4D2

OR5P2
OR3A1
OR52D1
OR10H1
OR5P3

OR2K2
OR51A10P
OR51I1
OR2N1P
OR12D3

OR2H1
OR7D2
OR51A1P
OR12D2
OR2H2

OR10A5
OR1D5
OR1G1
OR7E12P
OR2B6

OR4C1P
OR1C1
OR51J1
OR7E156P
OR8G1

OR2B3
OR8D1
OR10D1P
OR7C2
OR10H3

OR1J4
OR8D2
OR4D1
OR1E3
OR5I1

OR51B4
OR51B6
OR4F16
OR1I1
OR51B5

OR7E19P
OR7C1
OR51B2
OR7E37P
OR5V1

OR2L2
OR14J1
OR1E1
OR7E104P

TABLE 6

Human olfactory receptors expressed in coronaries or found in BIKE dataset

Gene
Controls NXT_A5
Case NXT_B5
GFOLD(0.01)
OR

ENSG00000221858.3
0
22.0390932
1.54166
OR2A12

ENSG00000184698.5
2.13789161
28.4812714
1.3736
OR51M1

ENSG00000185385.4
68.9845498
177.591567
0.789019
OR7A17

ENSG00000167332.8
30.0670845
85.1835567
0.686353
OR51E2

ENSG00000231319.3
0
12.2247952
0.508248
OR2B3

ENSG00000094661.3
181.6724
302.355662
0.299551
OR1I1

ENSG00000204695.4
377.706822
556.177204
0.210455
OR14J1

ENSG00000213215.5
21.0860876
46.3028088
0.189909
OR2F1

ENSG00000182070.5
76.7592432
131.555004
0.177862
OR52A1

ENSG00000203663.4
201.99031
291.13782
0.0984326
OR2L2

ENSG00000196184.9
49.1793067
85.5376168
0.0905611
OR10J1

ENSG00000167355.8
20.4650197
40.3322461
0.0112981
OR51B5

ENSG00000172146.2
276.518697
346.4817
0
OR1A1

ENSG00000184166.2
121.129162
132.773611
0
OR1D2

ENSG00000180785.9
110.761584
117.063217
0
OR51E1

ENSG00000188000.4
107.470536
136.721424
0
OR7D2

ENSG00000274052.2
85.9523142
63.7066912
0
OR7E156P

ENSG00000170683.6
49.5791167
67.8787387
0
OR10A3

ENSG00000159961.2
39.9535248
43.73905
0
OR3A3

ENSG00000221882.3
28.3044513
16.4305549
0
OR3A2

ENSG00000188269.9
27.7235813
31.5140557
0
OR7A5

ENSG00000197125.3
20.0233414
9.80312258
0
OR8B8

ENSG00000196341.3
14.429841
13.1216065
0
OR8D1

ENSG00000180658.4
13.4774257
4.35645584
0
OR2A4

ENSG00000141194.6
10.5631057
15.2371567
0
OR4D1

ENSG00000221888.4
7.80105605
3.0412225
0
OR1C1

ENSG00000197849.6
4.8214225
6.09046705
0
OR8G1

ENSG00000189398.5
2.63024582
0
0
OR7E12P

ENSG00000204657.4
1.91137294
1.01858945
0
OR2H2

ENSG00000225101.6
0.95302828
0
0
OR52K3P

ENSG00000274360.2
0
7.13113873
0
OR6W1P

ENSG00000225980.4
0
3.06023742
0
OR7E19P

ENSG00000171936.2
0
2.03745586
0
OR10H3

ENSG00000186723.4
169.65786
133.203895
−0.0897745
OR10H1

ENSG00000127530.3
386.176633
315.330905
−0.162011
OR7C1

ENSG00000170356.9
139.080996
69.1550135
−0.640902
OR2A20P

ENSG00000284768.1
15.8708554
0
−1.11392
OR2A12

ENSG00000257542.5
17.7745506
0
−1.30024
OR7E47P

ENSG00000180090.5
44.6279381
4.59413216
−1.66446
OR3A1

ENSG00000197309.3
23.8268405
0
−1.8117
OR10D3

ENSG00000219926.11
64.8293406
3.86557323
−2.49098
OR7E104P

ENSG00000168158.3
60.0437651
0
−3.18163
OR2C1

ENSG00000284791.1
88.3624998
0
−3.74841
OR7E47P

TABLE 7

Olfactory Receptor Screening-Top 17 expressed receptors with known

human orthologue and agonist

Mouse

Ortholog

(Ensemble

Gene Name
source)
Agonist
Known Antagonist

OR2B11
Olfr222
Coumarin

OR3A1
Olfr402
helional, Lilial
Methylcinnamaldehyde,

Hydrocinnamaldehyde,

Bourgeonal

OR4D6
Olfr1428
b-ionone

OR5A1
Olfr76
b-ionone

OR7C1
Olfr1352
Androstadienone

OR7D4
Olfr39
Androstenone,

Androstadienone

OR8D1
Olfr26
Caramel furanone

OR10A6
Olfr519
3-phenyl propyl

propienate

OR10G7
Olfr978
Eugenol

OR10G9
Olfr979
Ethil Vanillin

OR11A1
Olfr96
2-ethyl-fencol

OR11H6
Olfr745
Isovaleric Acid

OR51E1
Olfr558
Nonanoic acid,

Butyl

butyryllactate,

butyric acid,

isovaleric acid,

propionic acid

OR4E2
Olfr1509
N-amyl acetate

OR4D2
Olfr463
eugenol acetate

OR10H1
Olfr239
sandalwood

OR6A2
Olfr2
octanal

TABLE 8

Agonizing odorants: OLFR pairs

Odorant

Odorant

(agonist)
Olfactory receptor
(agonist)
Olfactory receptor

Lyral
OLFR16
vanillin
OR10G4 K295Q

azelaic acid
Olfr544 (human unknown)
2-methoxy-4-
OR10G7

methylphenol

propionic acid
OLFR78
banana
OR10G7

isoeugenol
OR10A6
eugenol
OR10G7

androstenone
OR10A6 A117V/V140G/L287P
eugenol methyl
OR10G7

ether

3-phenyl propyl
OR10A6 L287P
guaiacol
OR10G7

propionate

androstenone
OR10A6 L287P
jasmine
OR10G7

3-phenyl propyl
OR10A6 V140G/L287P
nutmeg
OR10G7

propionate

amyl laurate
OR10A6 V140G/L287P
spearmint
OR10G7

androstadienone
OR10A6 V140G/L287P
eugenol
OR10G7 T13M

androstenone
OR10A6 V140G/L287P
eugenol
OR10G7 T90A

butyric acid
OR10A6 V140G/L287P
sandalwood
OR10H1

isoeugenol
OR10A6 V140G/L287P
Santalol
OR10H1

cinnamon
OR10AG1
Sandranol
OR10H1

eugenol acetate
OR10G3
cinnamaldehyde
OR10H2

vanillin
OR10G3
geranyl acetate
OR10H2

vanillin
OR10G3 S73G
cinnamaldehyde
OR10H2 L40Q

vanillin
OR10G4
eugenol
OR10H5

2-methoxy-4-
OR10G4
lyral
OR10J5

methylphenol
A9V/M134V/V195E/R235G/K295Q

vanillin
OR10G4
α-cedrene
OR10J5

A9V/M134V/V195E/R235G/K295Q

2-decenal
OR14A2
Lyral
OR10J5

cis-3-hexen-1-ol
OR14J1
lyral
OR10J5 R233W

(+)-carvone
OR1A1
(−)-menthol
OR10X1

coumarin
OR1C1
2-ethylfenchol
OR11A1

linalool
OR1C1
isovaleric acid
OR11H4

geranyl acetate
OR1D2
isovaleric acid
OR11H6

bourgeonal
OR1D2
eugenol acetate
OR13C3 G2C

eugenol
OR1D5
sandalwood
OR14A16 Indel

isovaleric acid
OR1E1
cyclohexyl
OR2A4/7

salicylate

cinnamon
OR1N1
amyl butyrate
OR2AG1

cinnamon
OR1N1 P18S
isoeugenol
OR2AT4

linalool
OR1N2
Sandranol
OR2AT4

jasmine
OR1S2
Brahmanol
OR2AT4

jasmine
OR1S2 I46T
cinnamaldehyde
OR2B11

geranyl acetate
OR2A25
coffee difuran
OR2B11

quinoline
OR2A25
coumarin
OR2B11

geranyl acetate
OR2A25 A209P
dicyclohexyl
OR2B11

disulfide

geranyl acetate
OR2A25 S75N
quinoline
OR2B11

geranyl acetate
OR2A25 S75N/A209P
spearmint
OR2B11

quinoline
OR2A25 S75N/A209P
cis-3-hexen-1-
OR2J1 L12I

ol

cinnamaldehyde
OR2B11 I130S/V198M
androstenone
OR2J2

coffee difuran
OR2B11 V198M
butyl
OR2J2

anthranilate

coumarin
OR2B11 V198M
cis-3-hexen-1-
OR2J2

ol

quinoline
OR2B11 V198M
isovaleric acid
OR8U8

spearmint
OR2B11 V198M
cinnamaldehyde
OR9G1

coffee difuran
OR2B11 V198M/T293I/D300G
ethyl vanillin
OR2J2

coumarin
OR2B11 V198M/T293I/D300G
eugenol methyl
OR2J2

ether

quinoline
OR2B11 V198M/T293I/D300G
isoeugenol
OR2J2

spearmint
OR2B11 V198M/T293I/D300G
phenyl
OR2J2

acetaldehyde

1-octanethiol
OR2C1
androstenone
OR2J2 T111A

cinnamaldehyde
OR2C1
butyl
OR2J2 T111A

anthranilate

phenyl
OR2C1 C149W
cis-3-hexen-1-
OR2J2 T111A

acetaldehyde

ol

thioglycolic acid
OR2C1 C149W
ethyl vanillin
OR2J2 T111A

cinnamaldehyde
OR2C1
eugenol methyl
OR2J2 T111A

G16S/C149W/C169Y/R229H
ether

phenyl
OR2C1
isoeugenol
OR2J2 T111A

acetaldehyde
G16S/C149W/C169Y/R229H

eugenol acetate
OR2F1
phenyl
OR2J2 T111A

acetaldehyde

α-cedrene
OR2H2
ethyl vanillin
OR2J2

Y74H/T111A/V146A/T218A

aldehyde 13-13
OR2H2
isoeugenol
OR2J2

Y74H/T111A/V146A/T218A

cis-3-hexen-1-ol
OR2J3 I228V
phenyl
OR2J2

acetaldehyde
Y74H/T111A/V146A/T218A

ethylene
OR2J3 I228V
cinnamaldehyde
OR2J3

brassylate

geranyl acetate
OR2J3 I228V
cis-3-hexen-1-
OR2J3

ol

cinnamaldehyde
OR2J3 I228V/M261I
geranyl acetate
OR2J3

cis-3-hexen-1-ol
OR2J3 I228V/M261I
n-amyl acetate
OR2J3

eugenol methyl
OR2J3 I228V/M261I
cinnamaldehyde
OR2J3 I228V

ether

geranyl acetate
OR2J3 I228V/M261I
butyric acid
OR2T1 P132L

octyl aldehyde
OR2J3 I228V/M261I
sandalwood
OR2T1 P132L

spearmint
OR2J3 I228V/M261I
jasmine
OR2T6 N21D/C23G/S243A

cinnamaldehyde
OR2J3 R226Q/I228V/M261I
cis-3-hexen-1-
OR2W1

ol

cis-3-hexen-1-ol
OR2J3 R226Q/I228V/M261I
cis-3-hexen-1-
OR2W1 D296N

ol

geranyl acetate
OR2J3 R226Q/I228V/M2611
cis-3-hexen-1-
OR2W1 M81V

ol

cinnamaldehyde
OR2J3
cinnamon
OR3A1

T113A/R226Q/I228V/M261I

geranyl acetate
OR2M2 R220G/C235R
dihydrojasmone
OR3A1

geraniol
OR2M7
cinnamon
OR3A1 R125Q

geraniol
OR2M7 F35L/V78A/C178F
ethyl vanillin
OR3A1 R125Q

isoeugenol
OR2S2
jasmine
OR4A4

butyric acid
OR2T1
isovaleric acid
OR4C12 V283L

butyric acid
OR2T1 I76V
PI-23472
OR4D1

Nonanoic acid
OR51E1
eugenol acetate
OR4D2

isovaleric acid
OR51E1 K299R
eugenol acetate
OR4D2 C97S/L187F

isovaleric acid
OR51E1 SUN
eugenol acetate
OR4D2 L29I

propionic acid
OR51E2
androstenone
OR4F17

β-ionone
OR51E2
geranyl acetate
OR4L1 R52S

allyl
OR51L1
jasmine
OR4N4

phenylacetate

allyl
OR51L1 I281M
butyl
OR4Q3

phenylacetate

anthranilate

allyl
OR51L1 T196I/A207V
eugenol
OR4Q3

phenylacetate

eugenol
OR52B6
eugenol
OR4Q3 F238L

T36A/L90H/A146T/H149R/V267I

undecanal
OR56A4
jasmine
OR4X2

butyric acid
OR5AL1
Troenan
OR51B4

butyric acid
OR5AL1 Insertion
isononyl
OR51B5

alcohol

butyric acid
OR5D14
butyric acid
OR51D1

butyric acid
OR5D14 Q102L/S249A
isovaleric acid
OR51E1

eugenol methyl
OR5K1
androstadienone
OR7C1 V126I/E171K/S210P

ether

TMT
OR5K1
androstenone
OR7D4

coumarin
OR5P3
androstenone
OR7D4 P79L

eugenol methyl
OR6F1 F215L
androstenone
OR7D4 R88W/T133M

ether

anisaldehyde
OR6P1
butyric acid
OR7G2 V263A/F281V

phenyl
OR6P1
(+)-carvone
OR8B3

acetaldehyde

H20R/Q24R/V34I/M114I

Myrac
OR7A5
(−)-carvone
OR8B3

H20R/Q24R/V34I/M114I

androstadienone
OR7C1
r-carvone
OR8B3

H20R/Q24R/V34I/M114I

androstenone
OR7C1
caramel
OR8D1

furanone

androstadienone
OR7C1 S99G/V126I/E171K/S210P
sandalwood
OR8D1

eugenol acetate
OR9G1
(+)-menthol
OR8K3 L122R

Coumarin
OR2B11
(−)-menthol
OR8K3 L122R

helional, Lilial
OR3A1
Ethil Vanillin
OR10G9

b-ionone
OR4D6
2-ethyl-fencol
OR11A1

b-ionone
OR5A1
Isovaleric Acid
OR11H6

Androstadienone
OR7C1
Nonanoic acid,
OR51E1

Butyl

butyryllactate,

butyric acid,

isovaleric acid,

propionic acid

Androstenone,
OR7D4
N-amyl acetate
OR4E2

Androstadienone

Caramel
OR8D1
eugenol acetate
OR4D2

furanone

3-phenyl propyl
OR10A6
sandalwood
OR10H1

propienate

Eugenol
OR10G7
octanal
OR6A2

TABLE 9

Antagonistic odorants: OLFR pairs

Odorant (antagonistic)
Olfactory receptor

undecanal
OR17-4

undecanal
OR1D2

oxyphenylon
OR2AT4

phenirat
OR2AT4

methyl cinnamaldehyde
OR3A1

hydrocinamaldehyde
OR3A1

bourgeonal
OR3A1

ethylhexanoic acid
OR51E1

α-ionone
OR51E2

octanoic acid
ORs6

octanoic acid
ORs86

MODULATING IMMUNE RESPONSE VIA TARGETING OF OLFACTORY RECEPTOR ACTIVITY

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