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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod21

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod21 Module size 49 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 1586 CYP17A1 cytochrome P450 family 17 subfamily A member 1 1544 CYP1A2 cytochrome P450 family 1 subfamily A member 2 1589 CYP21A2 cytochrome P450 family 21 subfamily A member 2 1591 CYP24A1 cytochrome P450 family 24 subfamily A member 1 1592 CYP26A1 cytochrome P450 family 26 subfamily A member 1 56603 CYP26B1 cytochrome P450 family 26 subfamily B member 1 340665 CYP26C1 cytochrome P450 family 26 subfamily C member 1 1593 CYP27A1 cytochrome P450 family 27 subfamily A member 1 1594 CYP27B1 cytochrome P450 family 27 subfamily B member 1 339761 CYP27C1 cytochrome P450 family 27 subfamily C member 1 1553 CYP2A13 cytochrome P450 family 2 subfamily A member 13 1549 CYP2A7 cytochrome P450 family 2 subfamily A member 7 1555 CYP2B6 cytochrome P450 family 2 subfamily B member 6 1562 CYP2C18 cytochrome P450 family 2 subfamily C member 18 1557 CYP2C19 cytochrome P450 family 2 subfamily C member 19 1558 CYP2C8 cytochrome P450 family 2 subfamily C member 8 1559 CYP2C9 cytochrome P450 family 2 subfamily C member 9 1564 CYP2D6 cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene) 1572 CYP2F1 cytochrome P450 family 2 subfamily F member 1 1573 CYP2J2 cytochrome P450 family 2 subfamily J member 2 120227 CYP2R1 cytochrome P450 family 2 subfamily R member 1 29785 CYP2S1 cytochrome P450 family 2 subfamily S member 1 113612 CYP2U1 cytochrome P450 family 2 subfamily U member 1 54905 CYP2W1 cytochrome P450 family 2 subfamily W member 1 1576 CYP3A4 cytochrome P450 family 3 subfamily A member 4 64816 CYP3A43 cytochrome P450 family 3 subfamily A member 43 1577 CYP3A5 cytochrome P450 family 3 subfamily A member 5 1551 CYP3A7 cytochrome P450 family 3 subfamily A member 7 10858 CYP46A1 cytochrome P450 family 46 subfamily A member 1 1579 CYP4A11 cytochrome P450 family 4 subfamily A member 11 284541 CYP4A22 cytochrome P450 family 4 subfamily A member 22 1580 CYP4B1 cytochrome P450 family 4 subfamily B member 1 57834 CYP4F11 cytochrome P450 family 4 subfamily F member 11 66002 CYP4F12 cytochrome P450 family 4 subfamily F member 12 8529 CYP4F2 cytochrome P450 family 4 subfamily F member 2 126410 CYP4F22 cytochrome P450 family 4 subfamily F member 22 4051 CYP4F3 cytochrome P450 family 4 subfamily F member 3 285440 CYP4V2 cytochrome P450 family 4 subfamily V member 2 260293 CYP4X1 cytochrome P450 family 4 subfamily X member 1 199974 CYP4Z1 cytochrome P450 family 4 subfamily Z member 1 2326 FMO1 flavin containing monooxygenase 1 2329 FMO2 flavin containing monooxygenase 4 2328 FMO3 flavin containing monooxygenase 3 2329 FMO4 flavin containing monooxygenase 4 2330 FMO5 flavin containing monooxygenase 5 388714 FMO6P flavin containing monooxygenase 6 pseudogene 80020 FOXRED2 FAD dependent oxidoreductase domain containing 2 10424 PGRMC2 progesterone receptor membrane component 2 6916 TBXAS1 thromboxane A synthase 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 4.98e-01 3.92e-16 Reactome Vitamins Metabolism 3.11e-01 7.79e-79 GO monooxygenase activity molecular_function 2.86e-01 2.18e-08 Reactome FMO oxidises nucleophiles Metabolism 2.04e-01 6.73e-32 Reactome Miscellaneous substrates Metabolism 1.59e-01 1.18e-91 Reactome Cytochrome P450 - arranged by substrate type Metabolism 1.26e-01 1.75e-44 GO steroid hydroxylase activity molecular_function 7.92e-02 2.10e-82 GO organelle membrane cellular_component 7.25e-02 4.56e-36 Reactome Fatty acids Metabolism 4.75e-02 6.17e-41 GO aromatase activity molecular_function 2.58e-02 5.84e-11 GO retinoic acid 4-hydroxylase activity molecular_function 2.23e-02 2.68e-42 Reactome Xenobiotics Metabolism 1.54e-02 1.69e-83 GO heme binding molecular_function 2.82e-03 3.75e-81 GO iron ion binding molecular_function 1.36e-03 1.22e-87 Reactome Phase I - Functionalization of compounds Metabolism

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 response to xenobiotic stimulus 0e+00 0e+00 vitamin metabolic process 0e+00 0e+00 lipid catabolic process 0e+00 0e+00 xenobiotic metabolic process 0e+00 0e+00 cellular response to xenobiotic stimulus 0e+00 0e+00 monocarboxylic acid metabolic process 0e+00 0e+00 long-chain fatty acid metabolic process 0e+00 0e+00 epoxygenase P450 pathway 0e+00 0e+00 icosanoid metabolic process 0e+00 0e+00 arachidonic acid metabolic process 0e+00 0e+00 fatty acid metabolic process 0e+00 0e+00 drug catabolic process 0e+00 0e+00 exogenous drug catabolic process 0e+00 0e+00 omega-hydroxylase P450 pathway 0e+00 0e+00 drug metabolic process 0e+00 0e+00 oxidative demethylation 0e+00 0e+00 oxygen binding 0e+00 0e+00 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 0e+00 0e+00 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen

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 PHASE1 FUNCTIONALIZATION OF COMPOUNDS 0.00e+00 0.00e+00 CYTOCHROME P450 ARRANGED BY SUBSTRATE TYPE 0.00e+00 0.00e+00 BIOLOGICAL OXIDATIONS 0.00e+00 0.00e+00 XENOBIOTICS 0.00e+00 0.00e+00 PHASE1 FUNCTIONALIZATION OF COMPOUNDS 0.00e+00 0.00e+00 CYTOCHROME P450 ARRANGED BY SUBSTRATE TYPE 0.00e+00 0.00e+00 BIOLOGICAL OXIDATIONS 0.00e+00 0.00e+00 XENOBIOTICS 6.45e-07 1.50e-04 STEROID HORMONES 1.09e-06 2.46e-04 METABOLISM OF STEROID HORMONES AND VITAMINS A AND D 1.49e-06 2.52e-04 STEROID HORMONES 1.82e-06 3.04e-04 METABOLISM OF STEROID HORMONES AND VITAMINS A AND D 5.04e-06 1.01e-03 ENDOGENOUS STEROLS 5.41e-06 8.45e-04 ENDOGENOUS STEROLS 3.81e-03 3.65e-01 SYNTHESIS OF BILE ACIDS AND BILE SALTS VIA 24 HYDROXYCHOLESTEROL 4.77e-03 3.95e-01 SYNTHESIS OF BILE ACIDS AND BILE SALTS VIA 24 HYDROXYCHOLESTEROL 9.38e-03 7.61e-01 SYNTHESIS OF BILE ACIDS AND BILE SALTS 1.24e-02 9.44e-01 BILE ACID AND BILE SALT METABOLISM 1.83e-02 1.00e+00 SYNTHESIS OF BILE ACIDS AND BILE SALTS 2.91e-02 1.00e+00 BILE ACID AND BILE SALT METABOLISM

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.61e-05 9.37e-02 abnormal xenobiotic pharmacokinetics 1.21e-04 2.55e-01 abnormal vitamin D level 9.79e-04 8.93e-01 decreased physiological sensitivity to xenobiotic 1.59e-03 1.00e+00 abnormal hindlimb morphology 1.87e-03 1.00e+00 abnormal primitive urogenital sinus morphology 1.87e-03 1.00e+00 pelvic kidney 1.87e-03 1.00e+00 abnormal urinary system development 2.57e-03 1.00e+00 impaired skin barrier function 3.74e-03 1.00e+00 genital tubercle hypoplasia 3.74e-03 1.00e+00 abnormal ophthalmic nerve morphology 3.74e-03 1.00e+00 fused kidneys 7.47e-03 1.00e+00 sirenomelia 7.47e-03 1.00e+00 enlarged parathyroid gland 7.47e-03 1.00e+00 thickened long bone epiphysis 7.47e-03 1.00e+00 abnormal pulmonary alveolar duct morphology 7.48e-03 1.00e+00 abnormal mesonephros morphology 7.49e-03 1.00e+00 anovulation 1.06e-02 1.00e+00 abnormal kidney morphology 1.12e-02 1.00e+00 abnormal hindgut morphology 1.30e-02 1.00e+00 absent tail

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

²FDR corrected p-value (Benjamini-Hochberg)