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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod192

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod192 Module size 56 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 116984 ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2 392 ARHGAP1 Rho GTPase activating protein 1 9824 ARHGAP11A Rho GTPase activating protein 11A 89839 ARHGAP11B Rho GTPase activating protein 11B 55114 ARHGAP17 Rho GTPase activating protein 17 23092 ARHGAP26 Rho GTPase activating protein 26 9743 ARHGAP32 Rho GTPase activating protein 32 2909 ARHGAP35 Rho GTPase activating protein 35 394 ARHGAP5 Rho GTPase activating protein 5 395 ARHGAP6 Rho GTPase activating protein 6 9138 ARHGEF1 Rho guanine nucleotide exchange factor 1 9826 ARHGEF11 Rho guanine nucleotide exchange factor 11 23365 ARHGEF12 Rho guanine nucleotide exchange factor 12 50650 ARHGEF3 Rho guanine nucleotide exchange factor 3 54848 ARHGEF38 Rho guanine nucleotide exchange factor 38 9459 ARHGEF6 Rac/Cdc42 guanine nucleotide exchange factor 6 8874 ARHGEF7 Rho guanine nucleotide exchange factor 7 613 BCR BCR, RhoGEF and GTPase activating protein 1123 CHN1 chimerin 1 1124 CHN2 chimerin 2 8655 DLC1 dynein light chain LC8-type 1 55619 DOCK10 dedicator of cytokinesis 10 1894 ECT2 epithelial cell transforming 2 2665 GDI2 GDP dissociation inhibitor 2 3633 INPP5B inositol polyphosphate-5-phosphatase B 6453 ITSN1 intersectin 1 10103 NET1 tetraspanin 1 25791 NGEF neuronal guanine nucleotide exchange factor 84033 OBSCN obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF 5880 RAC2 Rac family small GTPase 2 5881 RAC3 Rac family small GTPase 3 10928 RALBP1 ralA binding protein 1 5924 RASGRF2 Ras protein specific guanine nucleotide releasing factor 2 387 RHOA ras homolog family member A 388 RHOB ras homolog family member B 9886 RHOBTB1 Rho related BTB domain containing 1 23221 RHOBTB2 Rho related BTB domain containing 2 389 RHOC ras homolog family member C 29984 RHOD ras homolog family member D 54509 RHOF ras homolog family member F, filopodia associated 391 RHOG ras homolog family member G 399 RHOH ras homolog family member H 57381 RHOJ ras homolog family member J 23433 RHOQ ras homolog family member Q 55288 RHOT1 ras homolog family member T1 58480 RHOU ras homolog family member U 171177 RHOV ras homolog family member V 6093 ROCK1 Rho associated coiled-coil containing protein kinase 1 201191 SAMD14 sterile alpha motif domain containing 14 6655 SOS2 SOS Ras/Rho guanine nucleotide exchange factor 2 9901 SRGAP2 SLIT-ROBO Rho GTPase activating protein 3 7074 TIAM1 T cell lymphoma invasion and metastasis 1 66000 TMEM108 transmembrane protein 108 7409 VAV1 vav guanine nucleotide exchange factor 1 7410 VAV2 vav guanine nucleotide exchange factor 2 10451 VAV3 vav guanine nucleotide exchange factor 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 1.59e-01 2.72e-108 Reactome Rho GTPase cycle Signal Transduction 1.20e-01 5.35e-105 GO regulation of small GTPase mediated signal transduction biological_process 8.53e-02 3.14e-43 GO Rho protein signal transduction biological_process 6.16e-02 1.04e-32 GO small GTPase mediated signal transduction biological_process 5.66e-02 1.54e-12 GO establishment or maintenance of actin cytoskeleton polarity biological_process 3.25e-02 1.22e-26 GO actin filament organization biological_process 2.85e-02 3.41e-11 Reactome Sema4D induced cell migration and growth-cone collapse Developmental Biology 1.75e-02 1.64e-11 GO cell projection assembly biological_process 1.68e-02 8.80e-13 Reactome Sema4D in semaphorin signaling Developmental Biology 1.55e-02 1.82e-06 GO engulfment of apoptotic cell biological_process 1.02e-02 9.67e-42 Reactome G alpha (12/13) signalling events Signal Transduction

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 regulation of Rho protein signal transduction 0.00e+00 0.00e+00 regulation of small GTPase mediated signal transduction 0.00e+00 0.00e+00 small GTPase mediated signal transduction 0.00e+00 0.00e+00 regulation of GTPase activity 0.00e+00 0.00e+00 regulation of Ras protein signal transduction 0.00e+00 0.00e+00 positive regulation of GTPase activity 0.00e+00 0.00e+00 actin filament-based process 0.00e+00 0.00e+00 actin cytoskeleton organization 0.00e+00 0.00e+00 Ras protein signal transduction 0.00e+00 0.00e+00 Rho protein signal transduction 0.00e+00 0.00e+00 Rho guanyl-nucleotide exchange factor activity 0.00e+00 0.00e+00 purine nucleoside binding 0.00e+00 0.00e+00 GTP binding 0.00e+00 0.00e+00 ribonucleoside binding 0.00e+00 0.00e+00 nucleoside binding 0.00e+00 0.00e+00 GTPase activator activity 0.00e+00 0.00e+00 GTPase regulator activity 1.03e-18 7.38e-16 enzyme activator activity 5.35e-18 3.80e-15 Ras guanyl-nucleotide exchange factor activity 1.09e-17 7.72e-15 guanyl-nucleotide exchange factor activity

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 SIGNALING BY RHO GTPASES 0.00e+00 0.00e+00 G ALPHA1213 SIGNALLING EVENTS 0.00e+00 0.00e+00 SEMA4D IN SEMAPHORIN SIGNALING 0.00e+00 0.00e+00 P75 NTR RECEPTOR MEDIATED SIGNALLING 0.00e+00 0.00e+00 NRAGE SIGNALS DEATH THROUGH JNK 0.00e+00 0.00e+00 CELL DEATH SIGNALLING VIA NRAGE NRIF AND NADE 0.00e+00 0.00e+00 SIGNALING BY RHO GTPASES 0.00e+00 0.00e+00 SEMA4D IN SEMAPHORIN SIGNALING 0.00e+00 0.00e+00 G ALPHA1213 SIGNALLING EVENTS 0.00e+00 0.00e+00 P75 NTR RECEPTOR MEDIATED SIGNALLING 0.00e+00 0.00e+00 SIGNALLING BY NGF 0.00e+00 0.00e+00 NRAGE SIGNALS DEATH THROUGH JNK 0.00e+00 0.00e+00 CELL DEATH SIGNALLING VIA NRAGE NRIF AND NADE 5.43e-11 2.01e-08 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 1.22e-10 3.30e-08 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 1.31e-09 4.28e-07 SIGNALLING BY NGF 4.49e-09 1.36e-06 SEMAPHORIN INTERACTIONS 5.19e-09 1.17e-06 SEMAPHORIN INTERACTIONS 6.44e-08 1.28e-05 GPVI MEDIATED ACTIVATION CASCADE 9.05e-07 1.58e-04 AXON GUIDANCE

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 6.27e-05 1.65e-01 increased circulating antidiuretic hormone level 7.60e-05 1.88e-01 abnormal lymphocyte cell number 2.41e-04 3.93e-01 decreased B cell proliferation 3.25e-04 4.72e-01 decreased anterior commissure size 4.77e-04 5.92e-01 increased circulating noradrenaline level 5.86e-04 6.66e-01 increased circulating adrenaline level 1.05e-03 9.25e-01 increased heart rate 1.20e-03 1.00e+00 increased renin activity 1.28e-03 1.00e+00 abnormal innervation 1.40e-03 1.00e+00 decreased creatinine clearance 1.49e-03 1.00e+00 abnormal adrenal gland secretion 1.57e-03 1.00e+00 decreased interleukin-2 secretion 1.67e-03 1.00e+00 renal fibrosis 2.20e-03 1.00e+00 abnormal aorta tunica media morphology 2.39e-03 1.00e+00 abnormal brain commissure morphology 2.54e-03 1.00e+00 decreased T cell proliferation 2.71e-03 1.00e+00 decreased mature B cell number 2.75e-03 1.00e+00 abnormal double-negative T cell morphology 2.78e-03 1.00e+00 abnormal B cell number 2.84e-03 1.00e+00 increased circulating renin level

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

²FDR corrected p-value (Benjamini-Hochberg)