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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod350

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod350 Module size 88 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 24153 A2M alpha-2-macroglobulin 9625 AATK apoptosis associated tyrosine kinase 642517 AGAP9 ArfGAP with GTPase domain, ankyrin repeat and PH domain 9 23647 ARFIP2 ADP ribosylation factor interacting protein 2 57584 ARHGAP21 Rho GTPase activating protein 21 201176 ARHGAP27 Rho GTPase activating protein 27 9639 ARHGEF10 Rho guanine nucleotide exchange factor 10 389337 ARHGEF37 Rho guanine nucleotide exchange factor 37 55701 ARHGEF40 Rho guanine nucleotide exchange factor 40 7984 ARHGEF5 Rho guanine nucleotide exchange factor 5 23229 ARHGEF9 Cdc42 guanine nucleotide exchange factor 9 151188 ARL6IP6 ADP ribosylation factor like GTPase 6 interacting protein 6 51374 ATRAID all-trans retinoic acid induced differentiation factor 576 BAI2 adhesion G protein-coupled receptor B2 293823 BNIP2 prune homolog 2 149428 BNIPL BCL2 interacting protein like 91768 CABLES1 Cdk5 and Abl enzyme substrate 1 26256 CABYR calcium binding tyrosine phosphorylation regulated 8618 CADPS calcium dependent secretion activator 550631 CCDC157 coiled-coil domain containing 157 998 CDC42 cell division cycle 42 11135 CDC42EP1 CDC42 effector protein 1 10435 CDC42EP2 CDC42 effector protein 2 9595 CYTIP cytohesin 1 interacting protein 50619 DEF6 DEF6, guanine nucleotide exchange factor 1730 DIAPH2 diaphanous related formin 2 80005 DOCK5 dedicator of cytokinesis 5 150368 FAM109B PH domain containing endocytic trafficking adaptor 2 389119 FAM212A inka box actin regulator 1 10160 FARP1 FERM, ARH/RhoGEF and pleckstrin domain protein 1 11153 FICD FIC domain containing 80144 FRAS1 Fraser extracellular matrix complex subunit 1 2800 GOLGA1 golgin A1 55889 GOLGA6B golgin A6 family member B 55204 GOLPH3L golgi phosphoprotein 3 like 26034 IPCEF1 interaction protein for cytohesin exchange factors 1 80183 KIAA0226L RUN and cysteine rich domain containing beclin 1 interacting protein like 23428 LAT2 solute carrier family 7 member 8 23284 LPHN3 adhesion G protein-coupled receptor L3 4478 MSN moesin 9788 MTSS1 MTSS1, I-BAR domain containing 339344 MYPOP Myb related transcription factor, partner of profilin 4689 NCF4 neutrophil cytosolic factor 4 203447 NRK Nik related kinase 4952 OCRL OCRL, inositol polyphosphate-5-phosphatase 5058 PAK1 p21 (RAC1) activated kinase 1 5062 PAK2 p21 (RAC1) activated kinase 2 5063 PAK3 p21 (RAC1) activated kinase 3 56924 PAK6 p21 (RAC1) activated kinase 6 57144 PAK7 p21 (RAC1) activated kinase 5 9260 PDLIM7 PDZ and LIM domain 7 5217 PFN2 profilin 2 8929 PHOX2B paired like homeobox 2B 5314 PKHD1 PKHD1, fibrocystin/polyductin 25894 PLEKHG4 pleckstrin homology and RhoGEF domain containing G4 153478 PLEKHG4B pleckstrin homology and RhoGEF domain containing G4B 55200 PLEKHG6 pleckstrin homology and RhoGEF domain containing G6 80243 PREX2 phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 51334 PRR16 proline rich 16 5662 PSD pleckstrin and Sec7 domain containing 9051 PSTPIP1 proline-serine-threonine phosphatase interacting protein 1 11159 RABL2A RAB, member of RAS oncogene family like 2A 5879 RAC1 Rac family small GTPase 1 29127 RACGAP1 Rac GTPase activating protein 1 57186 RALGAPA2 Ral GTPase activating protein catalytic alpha subunit 2 5910 RAP1GDS1 Rap1 GTPase-GDP dissociation stimulator 1 9462 RASAL2 RAS protein activator like 2 9986 RCE1 Ras converting CAAX endopeptidase 1 5962 RDX radixin 146206 RLTPR capping protein regulator and myosin 1 linker 2 6091 ROBO1 roundabout guidance receptor 1 6092 ROBO2 roundabout guidance receptor 2 9475 ROCK2 Rho associated coiled-coil containing protein kinase 2 6242 RTKN rhotekin 10507 SEMA4D semaphorin 4D 91404 SESTD1 SEC14 and spectrin domain containing 1 9644 SH3PXD2A SH3 and PX domains 2A 285590 SH3PXD2B SH3 and PX domains 2B 57630 SH3RF1 SH3 domain containing ring finger 1 26751 SH3YL1 SH3 and SYLF domain containing 1 9353 SLIT2 slit guidance ligand 2 9882 TBC1D4 TBC1 domain family member 4 51337 THEM6 thioesterase superfamily member 6 79838 TMC5 transmembrane channel like 5 22906 TRAK1 trafficking kinesin protein 1 7204 TRIO trio Rho guanine nucleotide exchange factor 5756 TWF1 twinfilin actin binding protein 1 55146 ZDHHC4 zinc finger DHHC-type containing 4

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 2.75e-01 3.82e-14 Reactome Activation of RAC1 Developmental Biology 1.28e-01 2.32e-08 Reactome Inactivation of CDC42 and RAC1 Developmental Biology 1.14e-01 1.07e-09 Reactome CD28 dependent Vav1 pathway Immune System 1.08e-01 9.39e-06 GO superoxide-generating NADPH oxidase activator activity molecular_function 6.38e-02 1.26e-07 GO phosphatidylinositol-4-phosphate binding molecular_function 5.20e-02 2.22e-05 GO positive regulation of pseudopodium assembly biological_process 4.46e-02 4.17e-11 GO positive regulation of stress fiber assembly biological_process 3.93e-02 9.67e-14 GO regulation of Rho protein signal transduction biological_process 3.71e-02 1.12e-04 Reactome Regulation of cortical dendrite branching Developmental Biology 3.61e-02 9.39e-06 Reactome Regulation of commissural axon pathfinding by SLIT and ROBO Developmental Biology 2.76e-02 8.28e-04 GO regulation of ruffle assembly biological_process 1.80e-02 4.30e-05 GO negative regulation of actin filament polymerization biological_process 1.45e-02 1.03e-12 GO Rho guanyl-nucleotide exchange factor activity molecular_function 1.34e-02 2.67e-08 Reactome RHO GTPases activate PAKs Signal Transduction 9.99e-03 5.45e-07 GO filopodium cellular_component 9.37e-03 4.07e-06 GO cleavage furrow cellular_component 6.73e-03 1.01e-04 GO GTP-Rho binding molecular_function 6.52e-03 3.59e-14 Reactome Rho GTPase cycle Signal Transduction 4.44e-03 2.22e-05 GO regulation of lamellipodium assembly biological_process 4.25e-03 1.21e-03 GO uropod cellular_component 6.98e-04 1.65e-17 Reactome Signaling by Rho GTPases Signal Transduction 2.87e-04 1.42e-03 GO positive regulation of cellular protein catabolic process biological_process

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 Rho guanyl-nucleotide exchange factor activity 3.19e-21 3.09e-18 regulation of GTPase activity 1.20e-19 1.15e-16 regulation of small GTPase mediated signal transduction 7.52e-18 7.16e-15 positive regulation of GTPase activity 1.30e-13 1.21e-10 regulation of Ras protein signal transduction 3.61e-12 2.45e-09 GTPase regulator activity 4.17e-11 2.62e-08 enzyme activator activity 7.55e-11 4.66e-08 GTPase activator activity 2.71e-09 1.91e-06 regulation of supramolecular fiber organization 3.67e-09 2.53e-06 regulation of actin cytoskeleton organization 7.41e-09 3.44e-06 guanyl-nucleotide exchange factor activity 1.03e-08 4.68e-06 Rho GTPase binding 2.33e-08 1.45e-05 regulation of actin filament-based process 4.66e-08 2.77e-05 regulation of cytoskeleton organization 9.06e-08 5.15e-05 regulation of cellular component size 1.52e-07 8.32e-05 regulation of actin filament bundle assembly 1.68e-07 9.13e-05 regulation of actin filament polymerization 4.08e-07 1.28e-04 cell leading edge 4.19e-07 2.13e-04 olfactory bulb interneuron development

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 ACTIVATION OF RAC 0.00e+00 0.00e+00 SIGNALING BY ROBO RECEPTOR 0.00e+00 0.00e+00 AXON GUIDANCE 0.00e+00 0.00e+00 ACTIVATION OF RAC 0.00e+00 0.00e+00 SIGNALING BY ROBO RECEPTOR 0.00e+00 0.00e+00 AXON GUIDANCE 9.79e-11 3.55e-08 DEVELOPMENTAL BIOLOGY 3.07e-07 5.68e-05 SEMAPHORIN INTERACTIONS 5.38e-07 9.81e-05 SIGNALING BY RHO GTPASES 1.02e-06 1.76e-04 NETRIN1 SIGNALING 1.29e-06 2.20e-04 CD28 DEPENDENT VAV1 PATHWAY 1.47e-06 3.23e-04 CD28 DEPENDENT VAV1 PATHWAY 2.09e-06 4.45e-04 NETRIN1 SIGNALING 2.68e-06 5.59e-04 SIGNALING BY RHO GTPASES 2.73e-06 5.69e-04 SEMAPHORIN INTERACTIONS 3.97e-06 6.31e-04 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 8.24e-06 1.25e-03 SEMA4D IN SEMAPHORIN SIGNALING 1.70e-05 3.12e-03 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 4.14e-05 7.07e-03 SEMA4D IN SEMAPHORIN SIGNALING 4.56e-05 6.13e-03 SEMA3A PAK DEPENDENT AXON REPULSION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.04e-04 2.32e-01 decreased hippocampal commissure size 3.96e-04 5.28e-01 abnormal neurite morphology 9.86e-04 8.95e-01 abnormal olfactory tract morphology 1.40e-03 1.00e+00 renal fibrosis 1.63e-03 1.00e+00 increased circulating amylase level 2.05e-03 1.00e+00 micrognathia 2.09e-03 1.00e+00 abnormal mammary gland duct morphology 3.69e-03 1.00e+00 abnormal ureteric bud morphology 3.99e-03 1.00e+00 hydroureter 4.33e-03 1.00e+00 abnormal mitral valve morphology 5.11e-03 1.00e+00 decreased paired-pulse facilitation 5.35e-03 1.00e+00 abnormal eye anterior chamber morphology 5.55e-03 1.00e+00 kidney cysts 7.51e-03 1.00e+00 abnormal brain interneuron morphology 8.12e-03 1.00e+00 abnormal ureter morphology 9.38e-03 1.00e+00 abnormal autonomic nervous system morphology 9.50e-03 1.00e+00 respiratory failure 1.12e-02 1.00e+00 abnormal petrosal ganglion morphology 1.12e-02 1.00e+00 mitral valve prolapse 1.25e-02 1.00e+00 enlarged liver

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

²FDR corrected p-value (Benjamini-Hochberg)