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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod66

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod66 Module size 94 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 65985 AACS acetoacetyl-CoA synthetase 13 AADAC arylacetamide deacetylase 344752 AADACL2 arylacetamide deacetylase like 2 126767 AADACL3 arylacetamide deacetylase like 3 343066 AADACL4 arylacetamide deacetylase like 4 60496 AASDHPPT aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase 215 ABCD1 ATP binding cassette subfamily D member 1 225 ABCD2 ATP binding cassette subfamily D member 2 5825 ABCD3 ATP binding cassette subfamily D member 3 31 ACACA acetyl-CoA carboxylase alpha 32 ACACB acetyl-CoA carboxylase beta 80724 ACAD10 acyl-CoA dehydrogenase family member 10 84129 ACAD11 acyl-CoA dehydrogenase family member 11 26027 ACOT11 acyl-CoA thioesterase 11 134526 ACOT12 acyl-CoA thioesterase 12 55856 ACOT13 acyl-CoA thioesterase 13 11332 ACOT7 acyl-CoA thioesterase 7 10005 ACOT8 acyl-CoA thioesterase 8 23597 ACOT9 acyl-CoA thioesterase 9 51 ACOX1 acyl-CoA oxidase 1 23205 ACSBG1 acyl-CoA synthetase bubblegum family member 1 81616 ACSBG2 acyl-CoA synthetase bubblegum family member 2 80221 ACSF2 acyl-CoA synthetase family member 2 197322 ACSF3 acyl-CoA synthetase family member 3 2180 ACSL1 acyl-CoA synthetase long chain family member 1 2181 ACSL3 acyl-CoA synthetase long chain family member 3 2182 ACSL4 acyl-CoA synthetase long chain family member 4 51703 ACSL5 acyl-CoA synthetase long chain family member 5 23305 ACSL6 acyl-CoA synthetase long chain family member 6 116285 ACSM1 acyl-CoA synthetase medium chain family member 1 123876 ACSM2A acyl-CoA synthetase medium chain family member 2A 348158 ACSM2B acyl-CoA synthetase medium chain family member 2B 6296 ACSM3 acyl-CoA synthetase medium chain family member 3 341392 ACSM4 acyl-CoA synthetase medium chain family member 4 54988 ACSM5 acyl-CoA synthetase medium chain family member 5 84532 ACSS1 acyl-CoA synthetase short chain family member 1 55902 ACSS2 acyl-CoA synthetase short chain family member 2 79611 ACSS3 acyl-CoA synthetase short chain family member 3 4329 ALDH6A1 aldehyde dehydrogenase 6 family member A1 56898 BDH2 3-hydroxybutyrate dehydrogenase 2 142827 C10orf129 acyl-CoA synthetase medium chain family member 6 165100 C2orf57 testis expressed 44 55322 C5orf22 chromosome 5 open reading frame 22 152206 CCDC13 coiled-coil domain containing 13 9425 CDYL chromodomain Y like 315330 CHAT extra spindle pole bodies like 1, separase 1374 CPT1A carnitine palmitoyltransferase 1A 1375 CPT1B carnitine palmitoyltransferase 1B 126129 CPT1C carnitine palmitoyltransferase 1C 1376 CPT2 carnitine palmitoyltransferase 2 1384 CRAT carnitine O-acetyltransferase 54677 CROT carnitine O-octanoyltransferase 1666 DECR1 2,4-dienoyl-CoA reductase 1 23181 DIP2A disco interacting protein 2 homolog A 57609 DIP2B disco interacting protein 2 homolog B 22982 DIP2C disco interacting protein 2 homolog C 1962 EHHADH enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase 79071 ELOVL6 ELOVL fatty acid elongase 6 55556 ENOSF1 enolase superfamily member 1 253152 EPHX4 epoxide hydrolase 4 55793 FAM63A MINDY lysine 48 deubiquitinase 1 54629 FAM63B MINDY lysine 48 deubiquitinase 2 2194 FASN fatty acid synthase 10249 GLYAT glycine-N-acyltransferase 26061 HACL1 2-hydroxyacyl-CoA lyase 1 3155 HMGCL 3-hydroxy-3-methylglutaryl-CoA lyase 3157 HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 3158 HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 3295 HSD17B4 hydroxysteroid 17-beta dehydrogenase 4 84263 HSDL2 hydroxysteroid dehydrogenase like 2 56922 MCCC1 methylcrotonoyl-CoA carboxylase 1 64087 MCCC2 methylcrotonoyl-CoA carboxylase 2 84693 MCEE methylmalonyl-CoA epimerase 23417 MLYCD malonyl-CoA decarboxylase 387254 MMAA solute carrier family 7 member 5 pseudogene 2 83661 MS4A8B membrane spanning 4-domains A8 4594 MUT methylmalonyl-CoA mutase 57552 NCEH1 neutral cholesterol ester hydrolase 1 55301 OLAH oleoyl-ACP hydrolase 5019 OXCT1 3-oxoacid CoA-transferase 1 5095 PCCA propionyl-CoA carboxylase subunit alpha 5096 PCCB propionyl-CoA carboxylase subunit beta 58488 PCTP phosphatidylcholine transfer protein 5264 PHYH phytanoyl-CoA 2-hydroxylase 5538 PPT1 palmitoyl-protein thioesterase 1 313200 SCP2 hydroxysteroid dehydrogenase like 2 140856 SCP2D1 SCP2 sterol binding domain containing 1 788 SLC25A20 solute carrier family 25 member 20 123096 SLC25A29 solute carrier family 25 member 29 283130 SLC25A45 solute carrier family 25 member 45 153328 SLC25A48 solute carrier family 25 member 48 284486 THEM5 thioesterase superfamily member 5 51300 TIMMDC1 translocase of inner mitochondrial membrane domain containing 1 29914 UBIAD1 UbiA prenyltransferase domain containing 1

Functional annotation

Modules were tested for enrichment in functional and pathway annotations using two complementary approaches:
1. To select a small number of specific / non-redundant annotations for each module, a regression-based approach was used;
2. To obtain the complete set of enriched annotations, an extension of Fisher’s exact test that takes annotation bias into account was employed (Wallenius’ non-central hypergeometric distribution).

Most specific annotations for this module

Coeff.1 P-value.2 Source.3 Term.4 Class.5 5.82e-01 5.59e-10 GO carnitine O-palmitoyltransferase activity molecular_function 4.78e-01 2.63e-12 Reactome Propionyl-CoA catabolism Metabolism 3.29e-01 2.54e-12 Reactome Ketone body metabolism Metabolism 3.19e-01 9.05e-35 GO acyl-CoA metabolic process biological_process 2.32e-01 1.61e-15 GO fatty acid beta-oxidation using acyl-CoA oxidase biological_process 1.81e-01 9.46e-14 GO long-chain fatty acid-CoA ligase activity molecular_function 1.69e-01 1.93e-08 Reactome TYSND1 cleaves peroxisomal proteins Metabolism of proteins 1.60e-01 5.40e-17 GO long-chain fatty-acyl-CoA biosynthetic process biological_process 1.52e-01 1.57e-11 Reactome Defective HLCS causes multiple carboxylase deficiency Disease 1.51e-01 1.57e-11 Reactome Defects in biotin (Btn) metabolism Disease 1.19e-01 1.02e-12 Reactome Amino Acid conjugation Metabolism 1.16e-01 1.02e-12 Reactome Conjugation of carboxylic acids Metabolism 8.24e-02 5.56e-12 Reactome Biotin transport and metabolism Metabolism 8.23e-02 8.12e-23 GO fatty acid beta-oxidation biological_process 6.94e-02 2.42e-05 Reactome Defective MMAA causes methylmalonic aciduria type cblA Disease 6.08e-02 4.42e-21 GO fatty acid biosynthetic process biological_process 5.96e-02 8.62e-22 Reactome Fatty acyl-CoA biosynthesis Metabolism 5.12e-02 8.45e-67 Reactome Fatty acid metabolism Metabolism 4.96e-02 6.43e-06 Reactome ChREBP activates metabolic gene expression Metabolism 4.68e-02 1.46e-10 Reactome Synthesis of Ketone Bodies Metabolism 4.66e-02 4.04e-06 GO very long-chain fatty acid catabolic process biological_process 2.89e-02 1.48e-02 Reactome Metabolism of vitamin K Metabolism 2.74e-02 3.44e-28 Reactome Mitochondrial Fatty Acid Beta-Oxidation Metabolism 1.80e-02 1.85e-12 GO carboxylic ester hydrolase activity molecular_function 1.62e-02 2.37e-07 Reactome Activation of gene expression by SREBF (SREBP) Metabolism 1.38e-02 2.42e-05 Reactome Conjugation of phenylacetate with glutamine Metabolism 1.12e-02 1.55e-03 GO ethanol oxidation biological_process 7.14e-03 1.37e-05 GO positive regulation of fatty acid beta-oxidation biological_process 3.08e-03 3.27e-10 Reactome Beta-oxidation of pristanoyl-CoA Metabolism 2.98e-03 1.55e-03 Reactome Ethanol oxidation Metabolism 2.53e-03 1.17e-04 GO catalytic activity molecular_function 5.60e-04 9.05e-05 Reactome ABC transporters in lipid homeostasis Transport of small molecules

¹Regression coefficient

²Fisher’s exact test nominal P-value

³Annotation source (Reactome, GO biological process (BP), molecular function (MF) and cellular component (CC))

⁴GO category or Reactome pathway

⁵High-level branch of annotation tree

Gene membership

All enriched annotations

Gene Ontology

P-value1 FDR2 Term 0.00e+00 0.00e+00 long-chain fatty acid transport 0.00e+00 0.00e+00 short-chain fatty acid metabolic process 0.00e+00 0.00e+00 peroxisome 0.00e+00 0.00e+00 peroxisomal matrix 0.00e+00 0.00e+00 CoA-ligase activity 0.00e+00 0.00e+00 thiolester hydrolase activity 0.00e+00 0.00e+00 acyl-CoA hydrolase activity 0.00e+00 0.00e+00 CoA hydrolase activity 0.00e+00 0.00e+00 acyl-CoA ligase activity 0.00e+00 0.00e+00 butyrate-CoA ligase activity 0.00e+00 0.00e+00 decanoate--CoA ligase activity 7.73e-67 7.63e-64 fatty acid metabolic process 2.41e-61 2.38e-58 monocarboxylic acid metabolic process 1.60e-50 1.58e-47 acyl-CoA metabolic process 1.30e-42 1.28e-39 cofactor metabolic process 9.00e-37 8.85e-34 sulfur compound metabolic process 2.67e-35 2.62e-32 fatty acid catabolic process 4.68e-34 3.41e-31 acid-thiol ligase activity 3.78e-33 3.71e-30 carboxylic acid catabolic process 6.48e-31 6.36e-28 long-chain fatty-acyl-CoA biosynthetic process

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 0.00e+00 0.00e+00 FATTY ACYL COA BIOSYNTHESIS 0.00e+00 0.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 0.00e+00 0.00e+00 PEROXISOMAL LIPID METABOLISM 0.00e+00 0.00e+00 FATTY ACYL COA BIOSYNTHESIS 0.00e+00 0.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 0.00e+00 0.00e+00 PEROXISOMAL LIPID METABOLISM 2.26e-10 5.94e-08 ALPHA LINOLENIC ACID ALA METABOLISM 2.83e-10 7.36e-08 ACTIVATED AMPK STIMULATES FATTY ACID OXIDATION IN MUSCLE 4.14e-10 1.42e-07 ALPHA LINOLENIC ACID ALA METABOLISM 2.23e-09 7.02e-07 TRIGLYCERIDE BIOSYNTHESIS 2.27e-09 5.30e-07 TRIGLYCERIDE BIOSYNTHESIS 3.39e-09 1.04e-06 SYNTHESIS OF VERY LONG CHAIN FATTY ACYL COAS 4.26e-09 9.66e-07 SYNTHESIS OF VERY LONG CHAIN FATTY ACYL COAS 1.12e-08 3.26e-06 ACTIVATED AMPK STIMULATES FATTY ACID OXIDATION IN MUSCLE 3.84e-08 1.04e-05 MITOCHONDRIAL FATTY ACID BETA OXIDATION 7.65e-07 1.35e-04 MITOCHONDRIAL FATTY ACID BETA OXIDATION 4.54e-05 6.11e-03 PPARA ACTIVATES GENE EXPRESSION 1.01e-04 1.57e-02 PPARA ACTIVATES GENE EXPRESSION 1.60e-04 2.36e-02 BRANCHED CHAIN AMINO ACID CATABOLISM 3.35e-04 3.79e-02 SYNTHESIS OF BILE ACIDS AND BILE SALTS VIA 7ALPHA HYDROXYCHOLESTEROL

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.66e-10 1.23e-05 increased fatty acid level 6.59e-07 6.48e-03 hepatic steatosis 3.95e-05 1.22e-01 abnormal lipid homeostasis 1.15e-04 2.48e-01 abnormal bile salt level 1.22e-04 2.57e-01 abnormal fatty acid oxidation 1.41e-04 2.85e-01 astrocytosis 2.16e-04 3.65e-01 decreased fatty acid level 3.26e-04 4.72e-01 abnormal lipid level 5.20e-04 6.20e-01 abnormal liver morphology 5.55e-04 6.46e-01 impaired adaptive thermogenesis 8.84e-04 8.39e-01 abnormal hepatocyte morphology 1.17e-03 9.85e-01 abnormal blood homeostasis 1.19e-03 9.96e-01 abnormal bile secretion 1.24e-03 1.00e+00 other phenotype 1.29e-03 1.00e+00 other aberrant phenotype 1.29e-03 1.00e+00 axon degeneration 1.38e-03 1.00e+00 increased circulating triglyceride level 1.47e-03 1.00e+00 Purkinje cell degeneration 2.01e-03 1.00e+00 decreased liver cholesterol level 2.24e-03 1.00e+00 hyperlipidemia

¹1Nominal enrichment p-value (Wallenius’ noncentral hypergeometric distribution)

²FDR corrected p-value (Benjamini-Hochberg)