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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod362

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod362 Module size 51 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 8751 ADAM15 ADAM metallopeptidase domain 15 84632 AFAP1L2 actin filament associated protein 1 like 2 9472 AKAP6 A-kinase anchoring protein 6 10077 ART1 tetraspanin 32 64921 CASD1 CAS1 domain containing 1 64866 CDCP1 CUB domain containing protein 1 6792 CDKL5 cyclin dependent kinase like 5 1398 CRK CRK proto-oncogene, adaptor protein 131566 DCBLD2 discoidin, CUB and LCCL domain containing 2 27120 DKKL1 dickkopf like acrosomal protein 1 1794 DOCK2 dedicator of cytokinesis 2 1795 DOCK3 dedicator of cytokinesis 3 9732 DOCK4 dedicator of cytokinesis 4 10278 EFS embryonal Fyn-associated substrate 79574 EPS8L3 EPS8 like 3 54206 ERRFI1 ERBB receptor feedback inhibitor 1 28964 GIT1 GIT ArfGAP 1 29998 GLTSCR1 BRD4 interacting chromatin remodeling complex associated protein 11250 GPR45 G protein-coupled receptor 45 3082 HGF hepatocyte growth factor 84941 HSH2D hematopoietic SH2 domain containing 8692 HYAL2 hyaluronidase 2 55243 KIRREL kirre like nephrin family adhesion molecule 1 259215 LY6G6F lymphocyte antigen 6 family member G6F 57591 MAL myocardin related transcription factor A 4301 MLLT4 afadin, adherens junction formation factor 344148 NCKAP5 NCK associated protein 5 4739 NEDD9 neural precursor cell expressed, developmentally down-regulated 9 10725 NFAT5 nuclear factor of activated T cells 5 4867 NPHP1 nephrocystin 1 4868 NPHS1 NPHS1, nephrin 64111 NPVF neuropeptide VF precursor 11248 NXPH3 neurexophilin 3 54873 PALMD palmdelphin 9749 PHACTR2 phosphatase and actin regulator 2 9050 PSTPIP2 proline-serine-threonine phosphatase interacting protein 2 9649 RALGPS1 Ral GEF with PH domain and SH3 binding motif 1 6098 ROS1 ROS proto-oncogene 1, receptor tyrosine kinase 57190 SEPN1 selenoprotein N 10045 SH2D3A SH2 domain containing 3A 400745 SH2D5 SH2 domain containing 5 23616 SH3BP1 SH3 domain binding protein 1 30011 SH3KBP1 SH3 domain containing kinase binding protein 1 112574 SNX18 sorting nexin 18 8470 SORBS2 sorbin and SH3 domain containing 2 6700 SPRR2A small proline rich protein 2A 80725 SRCIN1 SRC kinase signaling inhibitor 1 7039 TGFA transforming growth factor alpha 10188 TNK2 tyrosine kinase non receptor 2 84951 TNS4 tensin 4 56995 TULP4 tubby like protein 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 1.45e-01 6.68e-05 Reactome MET interacts with TNS proteins Signal Transduction 3.60e-02 1.33e-05 GO Rac guanyl-nucleotide exchange factor activity molecular_function 2.07e-02 1.86e-04 Reactome MET receptor recycling Signal Transduction 1.93e-02 4.04e-11 GO SH3 domain binding molecular_function 7.11e-03 1.06e-07 GO small GTPase mediated signal transduction biological_process 6.45e-03 5.14e-04 GO negative regulation of protein tyrosine kinase activity 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 7.28e-10 3.94e-07 SH3 domain binding 1.84e-07 9.94e-05 regulation of GTPase activity 2.85e-07 1.01e-04 protein domain specific binding 4.00e-06 1.69e-03 regulation of protein tyrosine kinase activity 4.72e-06 1.96e-03 positive regulation of GTPase activity 1.12e-05 4.29e-03 excretion 2.34e-05 8.25e-03 regulation of peptidyl-tyrosine phosphorylation 4.19e-05 1.38e-02 negative regulation of protein tyrosine kinase activity 4.78e-05 1.09e-02 signaling adaptor activity 7.05e-05 1.53e-02 binding, bridging 1.34e-04 2.53e-02 adherens junction 1.68e-04 3.25e-02 GTPase regulator activity 2.19e-04 5.66e-02 regulation of epidermal growth factor receptor signaling pathway 2.26e-04 5.81e-02 membrane raft polarization 3.13e-04 7.62e-02 membrane raft localization 3.61e-04 8.58e-02 regulation of ERBB signaling pathway 3.67e-04 6.42e-02 enzyme activator activity 3.71e-04 8.77e-02 negative regulation of peptidyl-tyrosine phosphorylation 4.16e-04 7.16e-02 guanyl-nucleotide exchange factor activity 4.93e-04 8.30e-02 SH3/SH2 adaptor activity

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.00e-03 1.00e-01 FACTORS INVOLVED IN MEGAKARYOCYTE DEVELOPMENT AND PLATELET PRODUCTION 1.72e-03 1.87e-01 HYALURONAN UPTAKE AND DEGRADATION 3.68e-03 3.54e-01 FACTORS INVOLVED IN MEGAKARYOCYTE DEVELOPMENT AND PLATELET PRODUCTION 6.65e-03 5.77e-01 HYALURONAN METABOLISM 9.20e-03 6.85e-01 SIGNALING BY ILS 1.26e-02 8.86e-01 P130CAS LINKAGE TO MAPK SIGNALING FOR INTEGRINS 1.62e-02 1.00e+00 IL 7 SIGNALING 2.18e-02 1.00e+00 DEFENSINS 2.21e-02 1.00e+00 SIGNAL ATTENUATION 2.51e-02 1.00e+00 INTEGRIN ALPHAIIB BETA3 SIGNALING 2.63e-02 1.00e+00 HYALURONAN UPTAKE AND DEGRADATION 2.86e-02 1.00e+00 ARMS MEDIATED ACTIVATION 3.04e-02 1.00e+00 REGULATION OF SIGNALING BY CBL 3.10e-02 1.00e+00 HYALURONAN METABOLISM 3.21e-02 1.00e+00 PROLONGED ERK ACTIVATION EVENTS 3.33e-02 1.00e+00 THE ROLE OF NEF IN HIV1 REPLICATION AND DISEASE PATHOGENESIS 3.35e-02 1.00e+00 NEPHRIN INTERACTIONS 3.69e-02 1.00e+00 SIGNALING BY ILS 3.71e-02 1.00e+00 SIGNAL ATTENUATION 3.93e-02 1.00e+00 PLATELET AGGREGATION PLUG FORMATION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.88e-03 1e+00 abnormal orbit morphology 2.01e-03 1e+00 dilated proximal convoluted tubules 2.49e-03 1e+00 hypoactivity 2.81e-03 1e+00 abnormal lung development 3.42e-03 1e+00 mesangial cell hyperplasia 4.47e-03 1e+00 spontaneous skin ulceration 5.58e-03 1e+00 abnormal coat/ hair morphology 5.62e-03 1e+00 small caput epididymis 5.75e-03 1e+00 expanded mesangial matrix 5.88e-03 1e+00 abnormal vibrissa morphology 6.03e-03 1e+00 spleen hypoplasia 7.19e-03 1e+00 impaired cued conditioning behavior 7.48e-03 1e+00 thick ears 7.48e-03 1e+00 absent Descemet membrane 8.68e-03 1e+00 abnormal object recognition memory 9.11e-03 1e+00 delayed fertilization 9.34e-03 1e+00 absent neural folds 9.34e-03 1e+00 abnormal nasal mucosa morphology 9.88e-03 1e+00 lymph node hypoplasia 1.11e-02 1e+00 abnormal dendritic spine morphology

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

²FDR corrected p-value (Benjamini-Hochberg)