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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod248

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod248 Module size 74 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 238 ALK ALK receptor tyrosine kinase 284 ANGPT1 angiopoietin 1 80831 APOL5 apolipoprotein L5 497258 BDNF BDNF antisense RNA 29760 BLNK B cell linker 867 CBL Cbl proto-oncogene 930 CD19 CD19 molecule 933 CD22 CD22 molecule 23607 CD2AP CD2 associated protein 971 CD72 CD72 molecule 973 CD79A CD79a molecule 974 CD79B CD79b molecule 1399 CRKL CRK like proto-oncogene, adaptor protein 27071 DAPP1 dual adaptor of phosphotyrosine and 3-phosphoinositides 1 420 DOK1 ADP-ribosyltransferase 4 (Dombrock blood group) 79930 DOK3 docking protein 3 55715 DOK4 docking protein 4 220164 DOK6 docking protein 6 2064 ERBB2 erb-b2 receptor tyrosine kinase 2 2260 FLG fibroblast growth factor receptor 1 10818 FRS2 fibroblast growth factor receptor substrate 2 10817 FRS3 fibroblast growth factor receptor substrate 3 128869 GAB1 phosphatidylinositol glycan anchor biosynthesis class U 9846 GAB2 GRB2 associated binding protein 2 139716 GAB3 GRB2 associated binding protein 3 128954 GAB4 GRB2 associated binding protein family member 4 25454 GDNF GDNF family receptor alpha 1 2674 GFRA1 GDNF family receptor alpha 1 2887 GRB10 growth factor receptor bound protein 10 2885 GRB2 growth factor receptor bound protein 2 2886 GRB7 growth factor receptor bound protein 7 3059 HCLS1 hematopoietic cell-specific Lyn substrate 1 10870 HCST hematopoietic cell signal transducer 29851 ICOS inducible T cell costimulator 3635 INPP5D inositol polyphosphate-5-phosphatase D 3667 IRS1 insulin receptor substrate 1 8471 IRS4 insulin receptor substrate 4 4254 KITLG KIT ligand 4058 LTK leukocyte receptor tyrosine kinase 56955 MEPE matrix extracellular phosphoglycoprotein 4486 MST1R macrophage stimulating 1 receptor 4690 NCK1 NCK adaptor protein 1 8440 NCK2 NCK adaptor protein 2 4804 NGFR nerve growth factor receptor 4908 NTF3 neurotrophin 3 4915 NTRK2 neurotrophic receptor tyrosine kinase 2 4916 NTRK3 neurotrophic receptor tyrosine kinase 3 5154 PDGFA platelet derived growth factor subunit A 5155 PDGFB platelet derived growth factor subunit B 118788 PIK3AP1 phosphoinositide-3-kinase adaptor protein 1 5295 PIK3R1 phosphoinositide-3-kinase regulatory subunit 1 5296 PIK3R2 phosphoinositide-3-kinase regulatory subunit 2 8503 PIK3R3 phosphoinositide-3-kinase regulatory subunit 3 23533 PIK3R5 phosphoinositide-3-kinase regulatory subunit 5 5335 PLCG1 phospholipase C gamma 1 5336 PLCG2 phospholipase C gamma 2 5587 PRKD1 protein kinase D1 5770 PTPN1 protein tyrosine phosphatase, non-receptor type 1 5781 PTPN11 protein tyrosine phosphatase, non-receptor type 11 5795 PTPRJ protein tyrosine phosphatase, receptor type J 2889 RAPGEF1 Rap guanine nucleotide exchange factor 1 5921 RASA1 RAS p21 protein activator 1 25970 SH2B1 SH2B adaptor protein 1 9047 SH2D2A SH2 domain containing 2A 10044 SH2D3C SH2 domain containing 3C 117186 SH3BP5 SH3-domain binding protein 5 79729 SH3D21 SH3 domain containing 21 6461 SHB SH2 domain containing adaptor protein B 6464 SHC1 SHC adaptor protein 1 25759 SHC2 SHC adaptor protein 2 53358 SHC3 SHC adaptor protein 3 399694 SHC4 SHC adaptor protein 4 8935 SKAP2 src kinase associated phosphoprotein 2 6654 SOS1 SOS Ras/Rac guanine nucleotide exchange factor 1

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 4.42e-01 1.73e-05 Reactome BDNF activates NTRK2 (TRKB) signaling Signal Transduction 3.03e-01 7.06e-08 Reactome Activated NTRK3 signals through PLCG1 Signal Transduction 2.76e-01 1.73e-05 Reactome NTF3 activates NTRK3 signaling Signal Transduction 2.16e-01 1.14e-35 Reactome RET signaling Developmental Biology 1.99e-01 1.31e-14 GO transmembrane receptor protein tyrosine kinase adaptor activity molecular_function 1.50e-01 9.96e-27 Reactome Downstream signal transduction Signal Transduction 1.34e-01 5.49e-15 Reactome Activated NTRK2 signals through FRS2 and FRS3 Signal Transduction 1.09e-01 2.88e-24 GO phosphotyrosine residue binding molecular_function 8.98e-02 2.86e-22 GO SH3/SH2 adaptor activity molecular_function 5.44e-02 3.52e-08 Reactome Frs2-mediated activation Signal Transduction 5.25e-02 5.85e-08 GO regulation of phosphatidylinositol 3-kinase activity biological_process 5.08e-02 2.62e-16 GO receptor tyrosine kinase binding molecular_function 3.37e-02 2.49e-18 Reactome Antigen activates B Cell Receptor (BCR) leading to generation of second messengers Immune System 3.35e-02 1.73e-05 Reactome NTF3 activates NTRK2 (TRKB) signaling Signal Transduction 2.73e-02 1.71e-22 GO phosphatidylinositol-4,5-bisphosphate 3-kinase activity molecular_function 2.25e-02 1.72e-04 Reactome GRB7 events in ERBB2 signaling Signal Transduction 2.08e-02 2.74e-12 GO insulin receptor binding molecular_function 1.79e-02 8.30e-06 GO phosphatidylinositol 3-kinase regulatory subunit binding molecular_function 1.31e-02 2.44e-13 GO positive regulation of phosphatidylinositol 3-kinase signaling biological_process 1.29e-02 9.30e-04 GO negative regulation of vascular permeability biological_process 1.19e-02 3.59e-23 GO positive regulation of protein kinase B signaling biological_process 9.71e-03 1.84e-21 Reactome Interleukin-3, Interleukin-5 and GM-CSF signaling Immune System 8.63e-03 2.79e-10 Reactome Signal attenuation Signal Transduction 6.82e-03 1.25e-02 Reactome Ceramide signalling Signal Transduction 6.65e-03 1.25e-02 Reactome NFG and proNGF binds to p75NTR Signal Transduction 6.20e-03 1.25e-02 Reactome Signaling by MST1 Signal Transduction 5.62e-03 1.61e-06 Reactome Negative regulation of MET activity Signal Transduction 2.79e-03 1.02e-07 GO platelet-derived growth factor receptor signaling pathway biological_process 2.76e-03 9.44e-41 Reactome Signaling by Receptor Tyrosine Kinases Signal Transduction 1.71e-03 1.25e-02 Reactome PTK6 Down-Regulation Signal Transduction 1.24e-03 4.12e-09 GO negative regulation of signal transduction biological_process 3.19e-04 1.19e-18 GO Ras guanyl-nucleotide exchange factor activity molecular_function

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 transmembrane receptor protein tyrosine kinase signaling pathway 0.00e+00 0.00e+00 enzyme linked receptor protein signaling pathway 0.00e+00 0.00e+00 insulin receptor binding 0.00e+00 0.00e+00 signaling adaptor activity 0.00e+00 0.00e+00 SH3/SH2 adaptor activity 3.75e-21 2.71e-18 receptor tyrosine kinase binding 3.40e-20 2.45e-17 protein tyrosine kinase binding 7.57e-19 5.43e-16 phosphatidylinositol 3-kinase activity 1.02e-18 7.32e-16 binding, bridging 3.05e-18 2.17e-15 protein binding, bridging 7.11e-18 5.04e-15 phosphatidylinositol-4,5-bisphosphate 3-kinase activity 8.61e-14 8.05e-11 phosphatidylinositol phosphorylation 2.12e-13 1.98e-10 lipid phosphorylation 5.04e-13 4.69e-10 regulation of phosphatidylinositol 3-kinase signaling 5.23e-13 4.86e-10 phosphatidylinositol metabolic process 9.40e-13 8.71e-10 axon guidance 1.01e-12 9.35e-10 neuron projection guidance 2.46e-12 2.26e-09 phosphatidylinositol-mediated signaling 2.71e-12 2.49e-09 inositol lipid-mediated signaling 5.68e-12 3.83e-09 Ras 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 ANTIGEN ACTIVATES B CELL RECEPTOR LEADING TO GENERATION OF SECOND MESSENGERS 0.00e+00 0.00e+00 ANTIGEN ACTIVATES B CELL RECEPTOR LEADING TO GENERATION OF SECOND MESSENGERS 0.00e+00 0.00e+00 SIGNAL ATTENUATION 2.59e-11 7.45e-09 IL 3 5 AND GM CSF SIGNALING 5.83e-10 1.97e-07 SIGNAL ATTENUATION 8.09e-10 1.99e-07 REGULATION OF SIGNALING BY CBL 4.77e-09 1.08e-06 TIE2 SIGNALING 1.93e-08 4.10e-06 DOWNSTREAM SIGNAL TRANSDUCTION 2.68e-08 5.62e-06 INSULIN RECEPTOR SIGNALLING CASCADE 2.71e-08 5.67e-06 SIGNALING BY CONSTITUTIVELY ACTIVE EGFR 8.16e-08 2.13e-05 IL 3 5 AND GM CSF SIGNALING 8.67e-08 2.24e-05 TIE2 SIGNALING 1.05e-07 2.70e-05 REGULATION OF SIGNALING BY CBL 1.07e-07 2.08e-05 SIGNALING BY INSULIN RECEPTOR 1.14e-07 2.20e-05 SIGNALING BY PDGF 1.33e-07 2.55e-05 IL RECEPTOR SHC SIGNALING 2.53e-07 4.73e-05 SIGNALLING TO ERKS 3.52e-07 6.49e-05 SIGNALING BY THE B CELL RECEPTOR BCR 8.13e-07 1.43e-04 SIGNALING BY ILS 9.97e-07 1.73e-04 SIGNALING BY SCF KIT

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.41e-07 1.83e-03 abnormal B cell differentiation 1.54e-07 1.98e-03 abnormal B cell physiology 2.34e-07 2.80e-03 decreased B cell proliferation 2.65e-07 3.09e-03 small petrosal ganglion 3.50e-07 3.92e-03 small dorsal root ganglion 6.78e-07 6.61e-03 decreased IgM level 7.46e-07 7.10e-03 abnormal B cell activation 8.04e-07 7.36e-03 abnormal sensory neuron morphology 1.40e-06 1.12e-02 small L4 dorsal root ganglion 3.82e-06 2.36e-02 abnormal muscle spindle morphology 7.67e-06 3.87e-02 increased pro-B cell number 7.98e-06 4.01e-02 small nodose ganglion 1.29e-05 5.64e-02 abnormal sensory neuron innervation pattern 2.82e-05 9.84e-02 arrested B cell differentiation 2.83e-05 9.84e-02 abnormal cranial ganglia morphology 3.02e-05 1.03e-01 decreased sensory neuron number 5.90e-05 1.59e-01 abnormal somatic nervous system morphology 1.10e-04 2.40e-01 decreased IgG3 level 1.58e-04 3.05e-01 small trigeminal ganglion 1.65e-04 3.13e-01 small cochlear ganglion

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

²FDR corrected p-value (Benjamini-Hochberg)