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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod271

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod271 Module size 45 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 23624 CBLC Cbl proto-oncogene C 1154 CISH cytokine inducible SH2 containing protein 293515 CNTF cardiotrophin 2 9244 CRLF1 cytokine receptor like factor 1 1437 CSF2 colony stimulating factor 2 1438 CSF2RA colony stimulating factor 2 receptor alpha subunit 1439 CSF2RB colony stimulating factor 2 receptor beta common subunit 1444 CSHL1 chorionic somatomammotropin hormone like 1 2056 EPO erythropoietin 2057 EPOR erythropoietin receptor 2688 GH1 growth hormone 1 2690 GHR growth hormone receptor 3456 IFNB1 interferon beta 1 3458 IFNG interferon gamma 171040 IL11 interleukin 11 3590 IL11RA interleukin 11 receptor subunit alpha 3593 IL12B interleukin 12B 3594 IL12RB1 interleukin 12 receptor subunit beta 1 3595 IL12RB2 interleukin 12 receptor subunit beta 2 116553 IL13 interleukin 13 3598 IL13RA2 interleukin 13 receptor subunit alpha 2 116562 IL2 interleukin 2 51561 IL23A interleukin 23 subunit alpha 149233 IL23R interleukin 23 receptor 3559 IL2RA interleukin 2 receptor subunit alpha 3560 IL2RB interleukin 2 receptor subunit beta 3561 IL2RG interleukin 2 receptor subunit gamma 24495 IL3 interleukin 3 133396 IL31RA interleukin 31 receptor A 287287 IL4 interleukin 4 24497 IL5 interleukin 5 24498 IL6 interleukin 6 3572 IL6ST interleukin 6 signal transducer 3976 LIF LIF, interleukin 6 family cytokine 4352 MPL MPL proto-oncogene, thrombopoietin receptor 5008 OSM oncostatin M 5617 PRL prolactin 5618 PRLR prolactin receptor 8651 SOCS1 suppressor of cytokine signaling 1 8835 SOCS2 suppressor of cytokine signaling 2 9021 SOCS3 suppressor of cytokine signaling 3 122809 SOCS4 suppressor of cytokine signaling 4 9655 SOCS5 suppressor of cytokine signaling 5 30837 SOCS7 suppressor of cytokine signaling 7 7173 TPO thyroid peroxidase

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 1.82e-01 1.12e-12 GO 1-phosphatidylinositol-3-kinase regulator activity molecular_function 1.33e-01 2.75e-17 Reactome IL-6-type cytokine receptor ligand interactions Immune System 1.32e-01 3.61e-26 GO cytokine receptor activity molecular_function 1.32e-01 5.96e-38 GO positive regulation of tyrosine phosphorylation of STAT protein biological_process 1.13e-01 1.12e-17 Reactome Interleukin receptor SHC signaling Immune System 1.00e-01 5.48e-16 Reactome Growth hormone receptor signaling Immune System 9.89e-02 1.43e-09 GO positive regulation of activation of Janus kinase activity biological_process 5.80e-02 4.63e-25 GO cytokine binding molecular_function 5.68e-02 1.74e-13 GO positive regulation of activated T cell proliferation biological_process 5.31e-02 5.99e-06 GO negative regulation of epidermal growth factor-activated receptor activity biological_process 4.41e-02 1.99e-06 Reactome RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) Gene expression (Transcription) 3.94e-02 1.34e-08 GO interleukin-2-mediated signaling pathway biological_process 3.72e-02 3.64e-06 GO positive regulation of immunoglobulin secretion biological_process 2.74e-02 9.93e-21 Reactome Interleukin-6 family signaling Immune System 2.27e-02 5.13e-09 GO positive regulation of T-helper 1 type immune response biological_process 1.49e-02 2.97e-11 GO positive regulation of JAK-STAT cascade biological_process 1.31e-02 2.04e-10 GO regulation of growth biological_process 8.39e-03 1.86e-04 Reactome Defective CSF2RA causes pulmonary surfactant metabolism dysfunction 4 (SMDP4) Disease 4.38e-03 1.86e-04 Reactome Defective CSF2RB causes pulmonary surfactant metabolism dysfunction 5 (SMDP5) Disease 4.35e-03 1.15e-18 Reactome Interleukin-4 and Interleukin-13 signaling Immune System 3.49e-03 2.61e-16 GO growth factor activity molecular_function 1.58e-03 1.86e-05 GO positive regulation of peptidyl-serine phosphorylation of STAT protein 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 0e+00 0e+00 response to cytokine 0e+00 0e+00 cytokine-mediated signaling pathway 0e+00 0e+00 cellular response to cytokine stimulus 0e+00 0e+00 positive regulation of tyrosine phosphorylation of STAT protein 0e+00 0e+00 regulation of peptidyl-tyrosine phosphorylation 0e+00 0e+00 positive regulation of peptidyl-tyrosine phosphorylation 0e+00 0e+00 regulation of JAK-STAT cascade 0e+00 0e+00 positive regulation of JAK-STAT cascade 0e+00 0e+00 positive regulation of tyrosine phosphorylation of Stat5 protein 0e+00 0e+00 regulation of tyrosine phosphorylation of Stat3 protein 0e+00 0e+00 positive regulation of tyrosine phosphorylation of Stat3 protein 0e+00 0e+00 JAK-STAT cascade 0e+00 0e+00 regulation of tyrosine phosphorylation of Stat1 protein 0e+00 0e+00 external side of plasma membrane 0e+00 0e+00 cell surface 0e+00 0e+00 cytokine receptor activity 0e+00 0e+00 cytokine binding 0e+00 0e+00 growth factor activity 0e+00 0e+00 cytokine activity 0e+00 0e+00 cytokine receptor binding

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 CYTOKINE SIGNALING IN IMMUNE SYSTEM 0.00e+00 0.00e+00 SIGNALING BY ILS 0.00e+00 0.00e+00 CYTOKINE SIGNALING IN IMMUNE SYSTEM 0.00e+00 0.00e+00 IL RECEPTOR SHC SIGNALING 0.00e+00 0.00e+00 GROWTH HORMONE RECEPTOR SIGNALING 1.62e-11 4.70e-09 IL 2 SIGNALING 3.56e-11 1.01e-08 IL 3 5 AND GM CSF SIGNALING 3.72e-10 1.28e-07 IL RECEPTOR SHC SIGNALING 1.54e-09 4.98e-07 GROWTH HORMONE RECEPTOR SIGNALING 3.08e-08 8.51e-06 IL 2 SIGNALING 3.92e-08 1.06e-05 IL 3 5 AND GM CSF SIGNALING 8.20e-08 2.13e-05 SIGNALING BY ILS 4.84e-06 7.62e-04 REGULATION OF IFNG SIGNALING 1.16e-05 1.71e-03 PROLACTIN RECEPTOR SIGNALING 1.17e-05 1.72e-03 IL 6 SIGNALING 4.32e-05 7.34e-03 PROLACTIN RECEPTOR SIGNALING 1.36e-04 1.68e-02 NUCLEAR SIGNALING BY ERBB4 1.92e-04 2.28e-02 REGULATION OF IFNA SIGNALING 5.87e-04 7.41e-02 IL 6 SIGNALING 1.01e-03 1.01e-01 INTERFERON ALPHA BETA SIGNALING

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.97e-07 2.46e-03 increased susceptibility to parasitic infection 4.21e-06 2.56e-02 abnormal macrophage physiology 6.08e-06 3.29e-02 increased IgG2a level 9.15e-06 4.43e-02 decreased circulating interleukin-13 level 1.05e-05 4.84e-02 granulomatous inflammation 1.30e-05 5.67e-02 decreased IgE level 4.20e-05 1.28e-01 increased IgG2b level 4.26e-05 1.29e-01 increased interferon-gamma secretion 5.02e-05 1.43e-01 prolonged estrous cycle 6.45e-05 1.69e-01 altered susceptibility to infection 8.52e-05 2.04e-01 abnormal circulating cytokine level 9.33e-05 2.16e-01 increased IgE level 1.36e-04 2.79e-01 decreased interferon-gamma secretion 1.48e-04 2.93e-01 abnormal lymphocyte physiology 1.62e-04 3.10e-01 increased activated T cell number 1.68e-04 3.15e-01 decreased interleukin-4 secretion 1.77e-04 3.24e-01 abnormal response to transplant 2.38e-04 3.90e-01 abnormal dendritic cell antigen presentation 2.50e-04 3.99e-01 decreased susceptibility to autoimmune disorder 2.67e-04 4.17e-01 decreased susceptibility to experimental autoimmune encephalomyelitis

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

²FDR corrected p-value (Benjamini-Hochberg)