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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod217

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod217 Module size 39 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 369 ARAF A-Raf proto-oncogene, serine/threonine kinase 673 BRAF B-Raf proto-oncogene, serine/threonine kinase 10256 CNKSR1 connector enhancer of kinase suppressor of Ras 1 22866 CNKSR2 connector enhancer of kinase suppressor of Ras 2 154043 CNKSR3 CNKSR family member 3 153090 DAB2IP DAB2 interacting protein 22844 FRMPD1 FERM and PDZ domain containing 1 84443 FRMPD3 FERM and PDZ domain containing 3 9758 FRMPD4 FERM and PDZ domain containing 4 3265 HRAS HRas proto-oncogene, GTPase 84966 IGSF21 immunoglobin superfamily member 21 3845 KRAS KRAS proto-oncogene, GTPase 8844 KSR1 kinase suppressor of ras 1 22866 KSR2 connector enhancer of kinase suppressor of Ras 2 79817 MOB3B MOB kinase activator 3B 4893 NRAS NRAS proto-oncogene, GTPase 5894 RAF1 Raf-1 proto-oncogene, serine/threonine kinase 5900 RALGDS ral guanine nucleotide dissociation stimulator 5906 RAP1A RAP1A, member of RAS oncogene family 5908 RAP1B RAP1B, member of RAS oncogene family 5909 RAP1GAP RAP1 GTPase activating protein 23108 RAP1GAP2 RAP1 GTPase activating protein 2 9693 RAPGEF2 Rap guanine nucleotide exchange factor 2 9771 RAPGEF5 Rap guanine nucleotide exchange factor 5 51735 RAPGEF6 Rap guanine nucleotide exchange factor 6 5922 RASA2 RAS p21 protein activator 2 22821 RASA3 RAS p21 protein activator 3 10156 RASA4 RAS p21 protein activator 4 100271927 RASA4B RAS p21 protein activator 4B 8437 RASAL1 RAS protein activator like 1 283349 RASSF5 Ras association domain family member 3 5863 RGL2 ral guanine nucleotide dissociation stimulator like 2 9610 RIN1 Ras and Rab interactor 1 6237 RRAS RAS related 401474 SAMD12 sterile alpha motif domain containing 12 57568 SIPA1L2 signal induced proliferation associated 1 like 2 65244 SPATS2 spermatogenesis associated serine rich 2 161742 SPRED1 sprouty related EVH1 domain containing 1 6793 STK10 serine/threonine kinase 10

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 2.59e-01 8.43e-08 GO Rap guanyl-nucleotide exchange factor activity molecular_function 2.41e-01 1.54e-38 Reactome Signaling by RAS mutants Disease 1.11e-01 3.38e-08 Reactome RAS signaling downstream of NF1 loss-of-function variants Disease 8.81e-02 1.38e-06 GO Ras GTPase binding molecular_function 7.55e-02 8.43e-08 Reactome Activation of RAS in B cells Immune System 5.65e-02 1.30e-10 Reactome Rap1 signalling Immune System 3.20e-02 3.79e-08 GO microvillus assembly biological_process 3.11e-02 1.11e-16 GO Ras protein signal transduction biological_process 2.02e-02 1.15e-08 Reactome p38MAPK events Signal Transduction 1.72e-02 1.59e-14 Reactome RAF activation Signal Transduction 1.67e-02 1.52e-04 GO establishment of protein localization to membrane biological_process 5.98e-03 7.63e-35 Reactome Oncogenic MAPK signaling Disease 3.90e-03 2.94e-07 Reactome SOS-mediated signalling Signal Transduction 3.65e-03 2.94e-07 Reactome GRB2 events in EGFR signaling 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 positive regulation of GTPase activity 0.00e+00 0.00e+00 regulation of small GTPase mediated signal transduction 0.00e+00 0.00e+00 regulation of GTPase activity 0.00e+00 0.00e+00 small GTPase mediated signal transduction 0.00e+00 0.00e+00 Ras protein signal transduction 6.70e-13 3.87e-10 intrinsic component of the cytoplasmic side of the plasma membrane 5.78e-11 3.60e-08 GTPase regulator activity 1.05e-10 8.69e-08 signal transduction by protein phosphorylation 2.63e-10 2.09e-07 regulation of Ras protein signal transduction 5.05e-10 3.89e-07 MAPK cascade 8.09e-10 4.36e-07 GTPase activator activity 4.49e-09 3.06e-06 negative regulation of Ras protein signal transduction 7.86e-09 5.17e-06 negative regulation of small GTPase mediated signal transduction 1.45e-07 5.44e-05 Rap guanyl-nucleotide exchange factor activity 2.02e-07 7.34e-05 mitogen-activated protein kinase kinase binding 2.10e-07 6.79e-05 cytoplasmic side of plasma membrane 2.11e-07 7.65e-05 enzyme activator activity 3.50e-07 1.11e-04 cytoplasmic side of membrane 6.69e-07 3.29e-04 regulation of MAPK cascade 1.11e-06 5.23e-04 regulation of ERK1 and ERK2 cascade

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.75e-09 4.15e-07 SIGNALLING TO ERKS 1.94e-09 4.58e-07 ARMS MEDIATED ACTIVATION 4.46e-09 1.01e-06 PROLONGED ERK ACTIVATION EVENTS 1.15e-08 2.50e-06 RAP1 SIGNALLING 2.37e-08 6.64e-06 ARMS MEDIATED ACTIVATION 4.89e-08 1.31e-05 SIGNALLING TO ERKS 5.28e-08 1.41e-05 PROLONGED ERK ACTIVATION EVENTS 5.35e-08 1.08e-05 SIGNALLING TO P38 VIA RIT AND RIN 7.05e-08 1.86e-05 RAP1 SIGNALLING 3.92e-07 9.37e-05 SIGNALLING TO P38 VIA RIT AND RIN 1.22e-06 2.09e-04 SIGNALLING TO RAS 1.47e-06 2.49e-04 RAF MAP KINASE CASCADE 1.64e-06 2.76e-04 P38MAPK EVENTS 4.58e-06 7.25e-04 SOS MEDIATED SIGNALLING 5.14e-06 1.03e-03 RAF MAP KINASE CASCADE 6.37e-06 9.83e-04 SHC MEDIATED SIGNALLING 7.06e-06 1.39e-03 P38MAPK EVENTS 9.14e-06 1.37e-03 SHC1 EVENTS IN EGFR SIGNALING 9.25e-06 1.38e-03 SHC RELATED EVENTS 9.56e-06 1.84e-03 SIGNALLING TO RAS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 3.21e-05 1.07e-01 increased cardiac muscle contractility 4.00e-04 5.32e-01 increased cardiac output 4.61e-04 5.78e-01 small placenta 5.41e-04 6.37e-01 abnormal snout morphology 8.42e-04 8.17e-01 heart hyperplasia 1.08e-03 9.40e-01 increased cranium width 1.26e-03 1.00e+00 chylous ascites 1.46e-03 1.00e+00 increased heart ventricle size 1.77e-03 1.00e+00 abnormal facial morphology 2.02e-03 1.00e+00 pale liver 2.93e-03 1.00e+00 enlarged spleen 3.19e-03 1.00e+00 decreased embryo weight 3.85e-03 1.00e+00 increased lung adenoma incidence 4.78e-03 1.00e+00 abnormal spongiotrophoblast layer morphology 5.59e-03 1.00e+00 ocular hypertelorism 6.62e-03 1.00e+00 increased systemic arterial diastolic blood pressure 6.65e-03 1.00e+00 decreased sensitivity to induced cell death 7.52e-03 1.00e+00 hemorrhage 8.49e-03 1.00e+00 hypertension 9.31e-03 1.00e+00 enlarged myocardial fiber

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

²FDR corrected p-value (Benjamini-Hochberg)