Weighted models for insulin Detected by scanone # transcripts that match weighted insulin model in each of 4 tissues: Detected by Ping’s multiQTL model tissue # transcripts Islet 1984 Adipose 605 Liver 485 Gastroc 404 Histogram of transcript-to-insulin correlations Islet – enrichment for 1984 transcripts Set GOCC GOCC GOCC GOBP GOBP GOBP GOBP GOBP GOBP GOMF GOMF GOBP GOBP GOBP GOBP GOCC KEGG GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP Pvalue Qvalue 3.70E-06 0.0073 3.45E-05 0.0294 4.48E-05 0.0294 8.16E-05 0.0402 0.0002 0.0761 0.0003 0.0761 0.0004 0.0761 0.0004 0.0761 0.0004 0.0761 0.0003 0.0761 0.0003 0.0761 0.0006 0.0895 0.0006 0.0895 0.0012 0.1469 0.0012 0.1469 0.0011 0.1469 0.0013 0.1469 0.0025 0.2361 0.0029 0.2361 0.0029 0.2361 0.0033 0.2361 0.0034 0.2361 0.0035 0.2361 0.0036 0.2361 0.0043 0.2361 0.0047 0.2361 0.0047 0.2361 0.0047 0.2361 0.0047 0.2361 Count 192 177 220 37 66 11 35 35 35 381 3 44 44 3 3 536 6 93 3 46 4 22 5 16 7 2 2 2 6 Size 2037 1919 2483 279 623 48 281 281 281 4802 3 386 386 4 4 7011 17 1021 5 442 10 172 16 111 31 2 2 2 24 Term extracellular region part extracellular space extracellular region enzyme linked receptor protein signaling pathway nervous system development neuromuscular process cell projection organization and biogenesis cell part morphogenesis cell projection morphogenesis protein binding siRNA binding cell morphogenesis cellular structure morphogenesis axon choice point recognition rhythmic synaptic transmission membrane Polyunsaturated fatty acid biosynthesis anatomical structure morphogenesis retinol metabolic process cytoskeleton organization and biogenesis microtubule bundle formation transmembrane receptor protein tyrosine kinase signaling pathway regulation of catabolic process forebrain development neuromuscular process controlling balance rhythmic excitation protein amino acid de-ADP-ribosylation ventricular cardiac muscle cell development cytokinesis Islet – modules 17 2 16 14 19 12 9 chromosomes Insulin trait Islet – enrichment for modules Module BLUE GREEN PURPLE BLACK MAGENTA YELLOW RED BROWN TURQUOISE PINK Pvalue Qvalue Count Size 0.0005 0.0006 0.0009 0.0012 0.0008 0.0055 0.0056 0.0463 0.0470 0.0507 0.0593 0.0457 0.0970 0.0970 30 18 11 19 4 2 10 1068 511 241 590 76 20 707 0.0011 0.0078 2.54E-05 0.0001 0.0004 0.0005 0.0006 0.0009 0.0011 0.0012 0.0026 0.0026 0.0026 0.0017 0.0026 0.0057 0.0002 0.0003 0.0003 0.0004 0.0004 0.0092 0.0165 0.0138 0.0011 0.0040 0.0040 0.0040 0.0040 0.0041 0.0041 0.0041 0.0675 0.0675 0.0675 0.0619 0.0619 0.1442 0.0830 0.0830 0.0830 0.0830 0.0608 0.0612 7 2 7 5 5 5 5 5 4 4 7 7 7 2 5 4 17 10 7 40 2 4 2769 68 313 179 225 228 239 266 162 163 281 281 281 13 200 96 279 115 57 1021 14 384 Term biosynthetic process cellular lipid metabolic process lipid biosynthetic process lipid metabolic process phosphate transport intermediate filament-based process ion transport nucleobase, nucleoside, nucleotide and nucleic acid metabolic process sensory perception of sound cell cycle process microtubule-based process mitotic cell cycle M phase cell division cell cycle phase mitosis M phase of mitotic cell cycle cell projection organization and biogenesis cell part morphogenesis cell projection morphogenesis steroid hormone receptor signaling pathway reproductive process response to pheromone enzyme linked receptor protein signaling pathway morphogenesis of an epithelium morphogenesis of embryonic epithelium anatomical structure morphogenesis vesicle organization and biogenesis regulation of apoptosis Insulin chromosomes Adipose – enrichment for 605 transcripts Set GOCC GOMF GOBP GOBP KEGG GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP Pvalue Qvalue 4.87E-07 0.0005 9.54E-05 0.0531 0.0004 0.0846 0.0004 0.0846 0.0003 0.0846 0.0006 0.0886 0.0007 0.0886 0.0010 0.1077 0.0020 0.1790 0.0030 0.1790 0.0038 0.1790 0.0040 0.1790 0.0042 0.1790 0.0043 0.1790 0.0046 0.1790 0.0062 0.1790 0.0086 0.1790 0.0087 0.1790 0.0087 0.1790 0.0090 0.1790 0.0098 0.1790 0.0121 0.1790 0.0130 0.1790 0.0134 0.1790 0.0136 0.1790 0.0158 0.1790 0.0173 0.1790 0.0197 0.1790 0.0206 0.1790 Count 174 151 11 11 4 4 15 40 3 7 4 5 3 4 24 3 16 3 3 24 13 6 4 17 6 16 3 7 7 Size 5332 4801 132 135 12 17 237 993 11 79 27 44 14 28 558 16 340 18 18 590 257 79 38 388 81 364 23 113 114 Term cytoplasm catalytic activity hexose metabolic process monosaccharide metabolic process Circadian rhythm T cell selection cellular carbohydrate metabolic process intracellular signaling cascade inositol metabolic process positive regulation of signal transduction monosaccharide biosynthetic process cell redox homeostasis thymic T cell selection alcohol biosynthetic process catabolic process polyamine metabolic process carbohydrate metabolic process glucosamine metabolic process N-acetylglucosamine metabolic process lipid metabolic process alcohol metabolic process one-carbon compound metabolic process protein ubiquitination regulation of signal transduction carbohydrate biosynthetic process small GTPase mediated signal transduction amino sugar metabolic process peptidyl-amino acid modification lipid catabolic process Adipose – modules 19 2 9 14 17 12 chromosomes Insulin trait Adipose – enrichment for modules Module GREEN PINK BLACK YELLOW TURQUOISE BLUE PURPLE BROWN RED MAGENTA Pvalue Qvalue Count 0.014 0.0560 4 0.019 0.0654 1 0.001 0.0430 4 0.004 0.0516 5 0.015 0.0743 1 0.003 0.0366 2 0.007 0.0436 2 0.021 0.0684 1 0.002 0.0173 2 0.002 0.0173 3 0.007 0.0280 2 0.010 0.0287 2 0.014 0.0327 2 0.019 0.0342 2 0.001 0.0713 4 0.002 0.0713 2 0.002 0.0713 3 0.003 0.0713 10 1.60E-06 0.0004 4 4.90E-05 0.0023 3 0.0002 0.0039 7 0.0002 0.0054 7 0.0003 0.0061 3 0.0019 0.0652 3 0.0080 0.0869 3 0.0002 0.0234 3 0.0005 0.0234 2 0.0006 0.0234 3 0.0009 0.0234 2 0.0011 0.0260 2 0.0017 0.0346 2 0.0044 0.0446 2 0.0049 0.0446 2 0.0051 0.0446 2 0.0062 0.0446 2 0.0069 0.0475 3 0.0153 0.0969 1 0.0278 0.1410 1 0.0030 0.0789 2 0.0147 0.1436 1 Size 605 12 364 993 13 46 79 13 28 113 56 69 82 97 70 12 44 590 17 14 221 237 25 237 392 58 16 78 21 24 29 47 50 51 56 187 12 22 79 14 Term proteolysis nucleoside diphosphate metabolic process small GTPase mediated signal transduction intracellular signaling cascade cellular protein complex disassembly methylation one-carbon compound metabolic process sulfate transport response to hormone stimulus peptidyl-amino acid modification hemostasis regulation of body fluid levels lipid transport glycoprotein metabolic process rhythmic process negative regulation of blood pressure cell redox homeostasis lipid metabolic process T cell selection thymic T cell selection leukocyte activation cell activation hexose biosynthetic process synapse cell junction amine biosynthetic process polyamine metabolic process nitrogen compound biosynthetic process biogenic amine biosynthetic process amino acid derivative biosynthetic process sulfur compound biosynthetic process detection of abiotic stimulus inner ear morphogenesis detection of external stimulus ear morphogenesis positive regulation of cell proliferation hydrogen peroxide metabolic process cellular response to stimulus one-carbon compound metabolic process protein targeting to membrane Insulin chromosomes Liver – enrichment for 485 transcripts Set GOBP GOBP GOMF GOMF GOBP GOBP GOBP GOCC GOCC GOMF GOCC GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP Pvalue Qvalue 0.0005 0.0584 0.0006 0.0584 0.0005 0.0584 0.0009 0.0584 0.0012 0.0658 0.0016 0.0808 0.0020 0.0882 0.0023 0.0922 0.0024 0.0922 0.0026 0.0945 0.0028 0.0990 0.0036 0.1197 0.0044 0.1197 0.0048 0.1197 0.0055 0.1197 0.0063 0.1197 0.0070 0.1197 0.0076 0.1197 0.0106 0.1197 0.0109 0.1197 0.0109 0.1197 0.0109 0.1197 0.0122 0.1197 0.0122 0.1197 0.0138 0.1197 0.0144 0.1197 0.0144 0.1197 0.0149 0.1197 0.0151 0.1197 Count 4 4 114 3 3 11 3 180 9 5 9 3 4 6 5 7 4 3 6 3 3 3 3 3 5 7 6 3 6 Size 20 21 4801 11 12 205 14 8478 155 52 159 17 36 84 61 117 41 22 99 25 25 25 26 26 76 137 106 28 107 Term nucleotide catabolic process glutathione metabolic process catalytic activity nucleotidase activity response to dsRNA regulation of cell differentiation thymic T cell selection intracellular microsome transferase activity, transferring alkyl or aryl (other than methyl) groups vesicular fraction T cell selection regulation of lymphocyte differentiation microtubule-based movement sulfur metabolic process bone remodeling dendrite development positive regulation of T cell differentiation cytoskeleton-dependent intracellular transport bone mineralization fat cell differentiation positive regulation of lymphocyte differentiation regulation of ossification T cell differentiation in the thymus phosphate transport tissue remodeling ossification gene silencing biomineral formation Liver – modules 14 9 12 17 chromosomes Insulin trait Liver – enrichment for modules Module YELLOW GREEN RED BROWN TURQUOISE BLUE Pvalue Qvalue Count 0.0004 0.0592 2 0.0035 0.0634 7 0.0050 0.0634 2 0.0132 0.0144 0.0144 0.0090 0.0868 0.0882 0.0882 0.0128 1 1 1 1 0.0135 0.0162 0.0005 0.0007 0.0012 0.0015 0.0017 0.0021 0.0032 0.0067 0.0077 0.0020 0.0020 0.0022 0.0025 0.0025 0.0029 0.0036 0.0062 0.0054 0.0076 0.0082 0.0102 0.0109 0.0115 0.0123 0.0158 0.0177 0.0186 0.0170 0.0189 0.0210 0.0210 0.0210 0.0222 0.0310 0.0313 0.0313 0.0648 0.0648 0.0648 0.0648 0.0648 0.0648 0.0648 0.0648 0.0730 0.0764 0.0764 0.0764 0.0764 0.0764 0.0764 0.0764 1 2 2 2 2 2 2 2 2 2 4 4 3 3 2 2 3 4 8 2 2 2 5 4 2 2 3 Size Term 15 lamellipodium biogenesis 1021 anatomical structure morphogenesis 52 cell projection biogenesis negative regulation of protein amino acid 11 phosphorylation 12 negative regulation of phosphorylation 12 negative regulation of hydrolase activity 12 nucleoside diphosphate metabolic process antigen processing and presentation of peptide antigen 18 via MHC class I 266 cell cycle phase 14 thymic T cell selection 17 T cell selection 22 positive regulation of T cell differentiation 25 positive regulation of lymphocyte differentiation 26 T cell differentiation in the thymus 29 regulation of T cell differentiation 36 regulation of lymphocyte differentiation 53 positive regulation of T cell activation 340 regulation of cell proliferation 84 microtubule-based movement 40 protein polymerization 41 dendrite development 12 neuron recognition 12 response to dsRNA 45 protein modification by small protein conjugation 99 cytoskeleton-dependent intracellular transport 436 response to chemical stimulus 21 glutathione metabolic process 25 fat cell differentiation 26 regulation of ossification 250 gamete generation 164 chromatin modification 31 regulation of bone remodeling 32 regulation of tissue remodeling 100 response to bacterium Insulin chromosomes Gastroc – enrichment for 404 transcripts Set GOBP GOBP GOMF GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP GOBP Pvalue Qvalue 0.0003 0.1718 0.0012 0.1718 0.0012 0.1718 0.0019 0.1748 0.0047 0.1748 0.0065 0.1748 0.0075 0.1748 0.0080 0.1748 0.0089 0.1748 0.0093 0.1748 0.0094 0.1748 0.0123 0.1748 0.0123 0.1748 0.0125 0.1748 0.0125 0.1748 0.0134 0.1748 0.0148 0.1748 0.0155 0.1748 0.0157 0.1748 0.0163 0.1748 0.0172 0.1748 0.0174 0.1748 0.0178 0.1748 0.0181 0.1748 0.0191 0.1748 0.0198 0.1748 0.0198 0.1748 0.0198 0.1748 0.0199 0.1748 Count 4 3 5 28 68 112 112 71 4 77 5 2 2 3 3 15 3 4 119 4 2 3 21 7 76 2 2 2 12 Size 21 14 49 993 3246 5957 5980 3492 52 3869 82 11 11 31 31 503 33 61 6550 62 13 35 815 170 3923 14 14 14 388 Term response to toxin regulation of I-kappaB kinase/NF-kappaB cascade lipid transporter activity intracellular signaling cascade regulation of cellular process primary metabolic process cellular metabolic process regulation of biological process antigen processing and presentation biological regulation lipid transport response to metal ion positive regulation of I-kappaB kinase/NF-kappaB cascade neural crest cell development neural crest cell differentiation cell proliferation antigen processing and presentation of peptide antigen regulation of protein amino acid phosphorylation metabolic process regulation of MAP kinase activity embryonic forelimb morphogenesis I-kappaB kinase/NF-kappaB cascade positive regulation of cellular process heart development biopolymer metabolic process tricarboxylic acid cycle intermediate metabolic process response to inorganic substance dicarboxylic acid metabolic process regulation of signal transduction Gastroc – modules 14 2 12 16 19 17 9 Insulin trait chromosomes Gastroc – enrichment for modules Module GREEN YELLOW BLUE RED BLACK TURQUOISE BROWN PINK Pvalue Qvalue Count Size Term 0.0157 0.1870 1 15 vacuolar transport 0.0157 0.1870 1 15 lamellipodium biogenesis 0.0167 0.1870 1 16 activated T cell proliferation 0.0175 0.0472 1 13 regulation of protein polymerization 0.0177 0.0472 13 5957 primary metabolic process 0.0183 0.0472 13 5980 cellular metabolic process regulation of small GTPase mediated signal 0.0188 0.0472 2 157 transduction 0.0088 0.0231 13 3869 biological regulation 0.0102 0.0231 2 85 positive regulation of protein kinase activity 0.0114 0.0231 2 90 positive regulation of kinase activity 0.0116 0.0231 2 91 positive regulation of transferase activity 0.0161 0.0231 2 108 negative regulation of signal transduction 0.0180 0.0231 11 3246 regulation of cellular process 0.0188 0.1749 1 12 response to osmotic stress 0.0266 0.1930 1 17 gluconeogenesis antigen processing and presentation of peptide 0.0281 0.1930 1 18 antigen via MHC class I positive regulation of I-kappaB kinase/NF0.0058 0.0137 1 11 kappaB cascade 0.0074 0.0137 1 14 heart looping regulation of I-kappaB kinase/NF-kappaB 0.0074 0.0137 1 14 cascade 0.0013 0.0692 17 1294 post-translational protein modification 0.0018 0.0692 36 3923 biopolymer metabolic process 0.0024 0.0692 18 1488 protein modification process 0.0032 0.0692 18 1525 biopolymer modification 0.0003 0.0105 2 11 response to metal ion 0.0006 0.0151 2 14 response to inorganic substance antigen processing and presentation of peptide 0.0007 0.0159 2 16 antigen via MHC class II antigen processing and presentation of 0.0007 0.0159 2 16 exogenous peptide antigen via MHC class II antigen processing and presentation of peptide 0.0008 0.0163 2 17 or polysaccharide antigen via MHC class II antigen processing and presentation of 0.0009 0.0168 2 18 exogenous peptide antigen 0.0013 0.0212 2 21 response to toxin antigen processing and presentation of 0.0016 0.0226 2 23 exogenous antigen 0.0016 0.0153 2 82 hormone metabolic process 0.0083 0.0163 1 11 sequestering of lipid 0.0090 0.0173 1 12 negative regulation of hydrolase activity 0.0097 0.0176 1 13 proximal/distal pattern formation 0.0097 0.0176 1 13 embryonic forelimb morphogenesis Insulin chromosomes 4 tissues combined – modules Insulin trait Insulin adipose gastroc islet liver total turquoise 63 83 546 17 709 blue 20 8 308 12 348 brown 33 96 46 128 303 yellow 68 35 165 33 301 green 43 56 132 41 272 red 33 31 198 9 271 black 164 13 58 23 258 pink 32 28 88 98 246 magenta 53 9 149 11 222 purple 34 12 143 19 208 greenyellow 40 31 43 45 159 tan 3 1 106 1 111 salmon 19 1 1 48 69 total 605 404 1983 485 3477
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