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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod81

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod81 Module size 41 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 6718 AKR1D1 aldo-keto reductase family 1 member D1 316 AOX1 aldehyde oxidase 1 644 BLVRA biliverdin reductase A 645 BLVRB biliverdin reductase B 874 CBR3 carbonyl reductase 3 1066 CES2 carboxylesterase 1 1312 COMT catechol-O-methyltransferase 1584 CYP11B1 cytochrome P450 family 11 subfamily B member 1 1585 CYP11B2 cytochrome P450 family 11 subfamily B member 2 1588 CYP19A1 cytochrome P450 family 19 subfamily A member 1 1543 CYP1A1 cytochrome P450 family 1 subfamily A member 1 1545 CYP1B1 cytochrome P450 family 1 subfamily B member 1 2990 GUSB glucuronidase beta 3290 HSD11B1 hydroxysteroid 11-beta dehydrogenase 1 3291 HSD11B2 hydroxysteroid 11-beta dehydrogenase 2 3292 HSD17B1 hydroxysteroid 17-beta dehydrogenase 1 3294 HSD17B2 hydroxysteroid 17-beta dehydrogenase 2 3293 HSD17B3 hydroxysteroid 17-beta dehydrogenase 3 8630 HSD17B6 hydroxysteroid 17-beta dehydrogenase 6 3283 HSD3B1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 3284 HSD3B2 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 9365 KL klotho 6715 SRD5A1 steroid 5 alpha-reductase 1 79644 SRD5A3 steroid 5 alpha-reductase 3 6783 SULT1E1 sulfotransferase family 1E member 1 7358 UGDH UDP-glucose 6-dehydrogenase 54658 UGT1A1 UDP glucuronosyltransferase family 1 member A1 54575 UGT1A10 UDP glucuronosyltransferase family 1 member A10 54659 UGT1A3 UDP glucuronosyltransferase family 1 member A3 54657 UGT1A4 UDP glucuronosyltransferase family 1 member A4 54579 UGT1A5 UDP glucuronosyltransferase family 1 member A5 54578 UGT1A6 UDP glucuronosyltransferase family 1 member A6 54577 UGT1A7 UDP glucuronosyltransferase family 1 member A7 54576 UGT1A8 UDP glucuronosyltransferase family 1 member A8 54600 UGT1A9 UDP glucuronosyltransferase family 1 member A9 10941 UGT2A1 UDP glucuronosyltransferase family 2 member A1 complex locus 7363 UGT2B11 UDP glucuronosyltransferase family 2 member B4 7367 UGT2B17 UDP glucuronosyltransferase family 2 member B17 7363 UGT2B4 UDP glucuronosyltransferase family 2 member B4 7364 UGT2B7 UDP glucuronosyltransferase family 2 member B7 80146 UXS1 UDP-glucuronate decarboxylase 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 2.73e-01 3.52e-15 Reactome Glucocorticoid biosynthesis Metabolism 2.47e-01 9.79e-25 GO flavonoid glucuronidation biological_process 2.35e-01 5.56e-06 GO steroid 11-beta-monooxygenase activity molecular_function 2.20e-01 5.78e-14 GO estrogen metabolic process biological_process 1.93e-01 5.78e-14 GO androgen biosynthetic process biological_process 1.87e-01 1.19e-27 GO cellular glucuronidation biological_process 1.59e-01 3.22e-35 Reactome Glucuronidation Metabolism 1.40e-01 4.18e-10 Reactome Heme degradation Metabolism 1.31e-01 2.51e-07 Reactome Estrogen biosynthesis Metabolism 1.20e-01 2.00e-26 GO xenobiotic glucuronidation biological_process 1.02e-01 7.89e-25 Reactome Metabolism of steroid hormones Metabolism 6.44e-02 5.02e-33 GO UDP-glycosyltransferase activity molecular_function 6.08e-02 3.35e-12 Reactome Androgen biosynthesis Metabolism 3.36e-02 8.64e-14 GO steroid binding molecular_function 3.18e-02 1.54e-04 Reactome Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) Metabolism 2.91e-02 7.14e-03 Reactome FGFR1c and Klotho ligand binding and activation Signal Transduction 2.91e-02 7.14e-03 Reactome Vitamins B6 activation to pyridoxal phosphate Metabolism 2.36e-02 4.39e-07 GO coumarin metabolic process biological_process 1.90e-02 4.77e-03 Reactome Enzymatic degradation of Dopamine by monoamine oxidase Neuronal System 9.51e-04 2.49e-23 GO retinoic acid binding molecular_function

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 0e+00 0e+00 steroid metabolic process 0e+00 0e+00 regulation of hormone levels 0e+00 0e+00 lipid biosynthetic process 0e+00 0e+00 steroid biosynthetic process 0e+00 0e+00 glucocorticoid metabolic process 0e+00 0e+00 hormone metabolic process 0e+00 0e+00 hormone biosynthetic process 0e+00 0e+00 glucocorticoid biosynthetic process 0e+00 0e+00 estrogen metabolic process 0e+00 0e+00 androgen metabolic process 0e+00 0e+00 androgen biosynthetic process 0e+00 0e+00 carbohydrate metabolic process 0e+00 0e+00 response to xenobiotic stimulus 0e+00 0e+00 flavonoid metabolic process 0e+00 0e+00 monosaccharide metabolic process 0e+00 0e+00 xenobiotic glucuronidation 0e+00 0e+00 cellular glucuronidation 0e+00 0e+00 monocarboxylic acid metabolic process 0e+00 0e+00 xenobiotic metabolic process 0e+00 0e+00 cellular response to xenobiotic stimulus

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 METABOLISM OF STEROID HORMONES AND VITAMINS A AND D 0.00e+00 0.00e+00 BIOLOGICAL OXIDATIONS 0.00e+00 0.00e+00 STEROID HORMONES 0.00e+00 0.00e+00 PHASE II CONJUGATION 0.00e+00 0.00e+00 GLUCURONIDATION 0.00e+00 0.00e+00 METABOLISM OF STEROID HORMONES AND VITAMINS A AND D 0.00e+00 0.00e+00 BIOLOGICAL OXIDATIONS 0.00e+00 0.00e+00 STEROID HORMONES 0.00e+00 0.00e+00 PHASE II CONJUGATION 0.00e+00 0.00e+00 GLUCURONIDATION 4.08e-09 9.31e-07 ANDROGEN BIOSYNTHESIS 1.32e-08 3.81e-06 ANDROGEN BIOSYNTHESIS 1.08e-06 1.86e-04 ENDOGENOUS STEROLS 4.77e-06 9.58e-04 ENDOGENOUS STEROLS 7.88e-06 1.54e-03 CYTOCHROME P450 ARRANGED BY SUBSTRATE TYPE 2.38e-05 3.36e-03 METABOLISM OF PORPHYRINS 5.89e-05 9.69e-03 METABOLISM OF PORPHYRINS 6.23e-05 1.02e-02 PHASE1 FUNCTIONALIZATION OF COMPOUNDS 7.27e-05 9.49e-03 CYTOCHROME P450 ARRANGED BY SUBSTRATE TYPE 3.00e-04 3.43e-02 PHASE1 FUNCTIONALIZATION OF COMPOUNDS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.65e-04 3.13e-01 increased seminal vesicle weight 1.65e-04 3.13e-01 abnormal amniotic fluid composition 4.12e-04 5.40e-01 abnormal enzyme/coenzyme level 5.73e-04 6.58e-01 hypokalemia 9.93e-04 8.99e-01 decreased circulating aldosterone level 1.04e-03 9.21e-01 decreased circulating chloride level 1.09e-03 9.45e-01 abnormal kidney medulla morphology 1.29e-03 1.00e+00 abnormal xenobiotic pharmacokinetics 1.94e-03 1.00e+00 abnormal liver physiology 2.04e-03 1.00e+00 enlarged adrenal glands 3.76e-03 1.00e+00 decreased circulating corticosterone level 6.00e-03 1.00e+00 abnormal renal glomerulus morphology 6.44e-03 1.00e+00 decreased thymus weight 7.15e-03 1.00e+00 abnormal seminiferous tubule morphology 7.49e-03 1.00e+00 Leydig cell hypertrophy 7.67e-03 1.00e+00 Leydig cell hyperplasia 8.10e-03 1.00e+00 hypertension 1.01e-02 1.00e+00 abnormal sexual interaction 1.08e-02 1.00e+00 increased circulating corticosterone level 1.12e-02 1.00e+00 enlarged prostate gland

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

²FDR corrected p-value (Benjamini-Hochberg)