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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod239

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod239 Module size 77 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 231 AR aldo-keto reductase family 1 member B 221481 ARMC12 armadillo repeat containing 12 1822 ATN1 atrophin 1 148523 C1orf51 circadian associated repressor of transcription 56683 C21orf59 cilia and flagella associated protein 298 285464 CRIPAK cysteine rich PAK1 inhibitor 9166 EBAG9 estrogen receptor binding site associated, antigen, 9 26298 EHF ETS homologous factor 1997 ELF1 E74 like ETS transcription factor 1 1998 ELF2 E74 like ETS transcription factor 2 1999 ELF3 E74 like ETS transcription factor 3 2000 ELF4 E74 like ETS transcription factor 4 2001 ELF5 E74 like ETS transcription factor 5 83401 ELOVL3 ELOVL fatty acid elongase 3 3757 ERG potassium voltage-gated channel subfamily H member 2 2099 ESR1 estrogen receptor 1 2113 ETS1 ETS proto-oncogene 1, transcription factor 2114 ETS2 ETS proto-oncogene 2, transcription factor 2120 ETV6 ETS variant 6 51513 ETV7 ETS variant 7 400451 FAM174B family with sequence similarity 174 member B 2551 GABPA GA binding protein transcription factor subunit alpha 9687 GREB1 growth regulating estrogen receptor binding 1 23199 GSE1 Gse1 coiled-coil protein 55806 HR HR, lysine demethylase and nuclear receptor corepressor 3605 IL17A interleukin 17A 221037 JMJD1C jumonji domain containing 1C 51780 KDM3B lysine demethylase 3B 51348 KLRF1 killer cell lectin like receptor F1 84458 LCOR ligand dependent nuclear receptor corepressor 254251 LCORL ligand dependent nuclear receptor corepressor like 55791 LRIF1 ligand dependent nuclear receptor interacting factor 1 255374 MBLAC1 metallo-beta-lactamase domain containing 1 10150 MBNL2 muscleblind like splicing regulator 2 55796 MBNL3 muscleblind like splicing regulator 3 79812 MMRN2 multimerin 2 4350 MPG N-methylpurine DNA glycosylase 744 MPPED2 metallophosphoesterase domain containing 2 7978 MTERF mitochondrial transcription termination factor 1 8031 NCOA4 nuclear receptor coactivator 4 135112 NCOA7 nuclear receptor coactivator 7 644524 NKX2-4 NK2 homeobox 4 338322 NLRP10 NLR family pyrin domain containing 10 190 NR0B1 nuclear receptor subfamily 0 group B member 1 9971 NR1H4 nuclear receptor subfamily 1 group H member 4 8856 NR1I2 nuclear receptor subfamily 1 group I member 2 9970 NR1I3 nuclear receptor subfamily 1 group I member 3 7026 NR2F2 nuclear receptor subfamily 2 group F member 2 2908 NR3C1 nuclear receptor subfamily 3 group C member 1 4306 NR3C2 nuclear receptor subfamily 3 group C member 2 8013 NR4A3 nuclear receptor subfamily 4 group A member 3 2649 NR6A1 nuclear receptor subfamily 6 group A member 1 29982 NRBF2 nuclear receptor binding factor 2 8204 NRIP1 nuclear receptor interacting protein 1 133060 OTOP1 otopetrin 1 57326 PBXIP1 PBX homeobox interacting protein 1 10957 PNRC1 proline rich nuclear receptor coactivator 1 55629 PNRC2 proline rich nuclear receptor coactivator 2 5449 POU1F1 POU class 1 homeobox 1 5452 POU2F2 POU class 2 homeobox 2 7799 PRDM2 PR/SET domain 2 56729 RETN resistin 8501 SLC43A1 solute carrier family 43 member 1 85414 SLC45A3 solute carrier family 45 member 3 64783 SPEN RNA binding motif protein 15 152185 SPICE1 spindle and centriole associated protein 1 9038 TAAR5 trace amine associated receptor 5 6942 TCF20 transcription factor 20 7023 TFAP4 transcription factor AP-4 9032 TM4SF5 transmembrane 4 L six family member 5 113452 TMEM54 transmembrane protein 54 7141 TNP1 transition protein 1 286827 TRIM59 tripartite motif containing 59 91875 TTC5 tetratricopeptide repeat domain 5 64854 USP46 ubiquitin specific peptidase 46 7494 XBP1 X-box binding protein 1 9326 ZNHIT3 zinc finger HIT-type containing 3

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 1.18e-01 1.71e-06 GO thyroid hormone receptor activity molecular_function 1.11e-01 3.30e-17 Reactome Nuclear Receptor transcription pathway Gene expression (Transcription) 1.10e-01 2.03e-04 Reactome RUNX1 regulates transcription of genes involved in BCR signaling Gene expression (Transcription) 6.75e-02 1.74e-05 GO histone demethylase activity (H3-K9 specific) molecular_function 3.61e-02 1.74e-05 GO glucocorticoid receptor binding molecular_function 2.14e-02 1.11e-02 Reactome Cleavage of the damaged purine DNA Repair 1.42e-02 1.68e-06 GO RNA polymerase II transcription factor binding molecular_function 1.35e-02 9.44e-05 GO positive regulation of interleukin-6 secretion biological_process 1.20e-02 1.76e-06 GO steroid binding molecular_function 1.01e-02 8.81e-04 GO determination of adult lifespan biological_process 6.53e-03 1.11e-02 Reactome Depurination DNA Repair 5.70e-03 1.17e-09 Reactome SUMOylation of intracellular receptors Metabolism of proteins 5.51e-03 6.03e-04 GO Leydig cell differentiation biological_process 4.89e-03 4.58e-05 Reactome HSP90 chaperone cycle for steroid hormone receptors (SHR) Cellular responses to external stimuli 3.18e-03 8.81e-04 GO hypothalamus development biological_process 1.22e-03 1.11e-02 Reactome Recognition and association of DNA glycosylase with site containing an affected purine DNA Repair

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 steroid hormone mediated signaling pathway 0.00e+00 0.00e+00 intracellular receptor signaling pathway 0.00e+00 0.00e+00 cellular response to steroid hormone stimulus 0.00e+00 0.00e+00 hormone-mediated signaling pathway 1.41e-18 1.35e-15 transcription from RNA polymerase II promoter 3.69e-12 2.50e-09 transcription regulatory region sequence-specific DNA binding 7.91e-12 5.29e-09 RNA polymerase II transcription factor activity, sequence-specific DNA binding 1.24e-11 8.20e-09 transcription regulatory region DNA binding 1.26e-11 8.32e-09 regulatory region DNA binding 2.07e-11 1.83e-08 transcription initiation from RNA polymerase II promoter 3.64e-11 2.30e-08 double-stranded DNA binding 9.08e-11 5.56e-08 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding 1.60e-10 9.55e-08 steroid hormone receptor activity 5.71e-10 4.38e-07 DNA-templated transcription, initiation 7.85e-10 5.92e-07 response to steroid hormone 1.31e-09 6.81e-07 RNA polymerase II regulatory region sequence-specific DNA binding 1.37e-09 7.11e-07 RNA polymerase II regulatory region DNA binding 4.49e-09 3.06e-06 cellular response to lipid 1.35e-08 6.04e-06 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding 1.61e-08 1.02e-05 cellular response to hormone 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 NUCLEAR RECEPTOR TRANSCRIPTION PATHWAY 0.00e+00 0.00e+00 NUCLEAR RECEPTOR TRANSCRIPTION PATHWAY 6.66e-06 1.31e-03 GENERIC TRANSCRIPTION PATHWAY 2.22e-03 2.04e-01 CIRCADIAN CLOCK 1.24e-02 9.44e-01 CIRCADIAN CLOCK 2.15e-02 1.00e+00 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 2.16e-02 1.00e+00 CIRCADIAN REPRESSION OF EXPRESSION BY REV ERBA 2.48e-02 1.00e+00 ACTIVATION OF CHAPERONES BY ATF6 ALPHA 2.72e-02 1.00e+00 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 3.20e-02 1.00e+00 SYNTHESIS OF VERY LONG CHAIN FATTY ACYL COAS 3.35e-02 1.00e+00 ACTIVATION OF CHAPERONES BY ATF6 ALPHA 4.11e-02 1.00e+00 BMAL1 CLOCK NPAS2 ACTIVATES CIRCADIAN EXPRESSION 4.56e-02 1.00e+00 FATTY ACYL COA BIOSYNTHESIS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.38e-04 2.81e-01 abnormal peritubular myoid cell morphology 3.28e-04 4.72e-01 abnormal efferent ductules of testis morphology 4.90e-04 5.99e-01 dilated seminiferous tubules 1.08e-03 9.40e-01 abnormal physiological response to xenobiotic 1.61e-03 1.00e+00 decreased hippocampus pyramidal cell number 1.61e-03 1.00e+00 increased testis tumor incidence 2.79e-03 1.00e+00 absent trabeculae carneae 3.14e-03 1.00e+00 decreased circulating testosterone level 3.49e-03 1.00e+00 abnormal B cell differentiation 3.77e-03 1.00e+00 increased renin activity 4.36e-03 1.00e+00 translucent skin 5.08e-03 1.00e+00 decreased circulating prolactin level 6.32e-03 1.00e+00 impaired muscle relaxation 6.37e-03 1.00e+00 abnormal vestibular system physiology 6.54e-03 1.00e+00 abnormal bone marrow cell number 6.83e-03 1.00e+00 decreased NK cell number 6.96e-03 1.00e+00 increased circulating testosterone level 7.19e-03 1.00e+00 increased circulating aldosterone level 7.59e-03 1.00e+00 absent linear vestibular evoked potential 7.86e-03 1.00e+00 increased systemic arterial systolic blood pressure

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

²FDR corrected p-value (Benjamini-Hochberg)