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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod176

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod176 Module size 26 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 64625 BID BH3 interacting domain death agonist 329 BIRC2 baculoviral IAP repeat containing 2 330 BIRC3 baculoviral IAP repeat containing 3 843 CASP10 caspase 10 835 CASP2 caspase 2 836 CASP3 caspase 3 841 CASP8 caspase 8 8837 CFLAR CASP8 and FADD like apoptosis regulator 8738 CRADD CASP2 and RIPK1 domain containing adaptor with death domain 9191 DEDD death effector domain containing 8772 FADD Fas associated via death domain 2194 FAS fatty acid synthase 356 FASLG Fas ligand 2108 MADD electron transfer flavoprotein subunit alpha 9448 MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4 8996 NOL3 nucleolar protein 3 8439 NSMAF neutral sphingomyelinase activation associated factor 389643 NUGGC nuclear GTPase, germinal center associated 8797 TNFRSF10A TNF receptor superfamily member 10a 8795 TNFRSF10B TNF receptor superfamily member 10b 8794 TNFRSF10C TNF receptor superfamily member 10c 8793 TNFRSF10D TNF receptor superfamily member 10d 7132 TNFRSF1A TNF receptor superfamily member 1A 8718 TNFRSF25 TNF receptor superfamily member 25 8743 TNFSF10 TNF superfamily member 10 8717 TRADD TNFRSF1A associated via death domain

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 3.77e-01 7.53e-21 Reactome TRAIL signaling Signal Transduction 1.88e-01 3.51e-29 Reactome Regulation of necroptotic cell death Programmed Cell Death 1.48e-01 5.33e-20 GO death receptor binding molecular_function 1.01e-01 4.52e-17 GO death-inducing signaling complex cellular_component 9.15e-02 5.28e-15 Reactome FasL/ CD95L signaling Signal Transduction 9.13e-02 3.29e-05 Reactome TNFR1-mediated ceramide production Signal Transduction 5.07e-02 5.48e-22 GO extrinsic apoptotic signaling pathway via death domain receptors biological_process 4.15e-02 3.29e-05 Reactome NADE modulates death signalling Signal Transduction 3.66e-02 4.15e-12 Reactome TP53 Regulates Transcription of Death Receptors and Ligands Gene expression (Transcription) 3.34e-02 7.49e-18 Reactome TP53 Regulates Transcription of Cell Death Genes Gene expression (Transcription) 3.12e-02 2.55e-28 Reactome Regulated Necrosis Programmed Cell Death 3.10e-02 2.55e-28 Reactome RIPK1-mediated regulated necrosis Programmed Cell Death 3.02e-02 1.67e-25 GO regulation of extrinsic apoptotic signaling pathway via death domain receptors biological_process 2.59e-02 1.57e-11 GO cysteine-type endopeptidase activity involved in apoptotic process molecular_function 1.36e-02 3.03e-03 Reactome Activation and oligomerization of BAK protein Programmed Cell Death 1.22e-02 1.35e-09 GO negative regulation of necroptotic process biological_process 7.33e-03 1.03e-17 GO tumor necrosis factor-mediated signaling pathway biological_process 1.42e-03 1.75e-10 GO execution phase of apoptosis 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 apoptotic signaling pathway 0e+00 0e+00 extrinsic apoptotic signaling pathway 0e+00 0e+00 extrinsic apoptotic signaling pathway via death domain receptors 0e+00 0e+00 regulation of cysteine-type endopeptidase activity 0e+00 0e+00 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors 0e+00 0e+00 regulation of extrinsic apoptotic signaling pathway via death domain receptors 0e+00 0e+00 positive regulation of cysteine-type endopeptidase activity 0e+00 0e+00 regulation of extrinsic apoptotic signaling pathway 0e+00 0e+00 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway 0e+00 0e+00 activation of cysteine-type endopeptidase activity involved in apoptotic process 0e+00 0e+00 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process 0e+00 0e+00 regulation of cysteine-type endopeptidase activity involved in apoptotic process 0e+00 0e+00 regulation of endopeptidase activity 0e+00 0e+00 regulation of peptidase activity 0e+00 0e+00 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway 0e+00 0e+00 positive regulation of peptidase activity 0e+00 0e+00 positive regulation of endopeptidase activity 0e+00 0e+00 membrane raft 0e+00 0e+00 death-inducing signaling complex 0e+00 0e+00 membrane microdomain

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 EXTRINSIC PATHWAY FOR APOPTOSIS 0.00e+00 0.00e+00 EXTRINSIC PATHWAY FOR APOPTOSIS 0.00e+00 0.00e+00 APOPTOSIS 1.44e-10 5.17e-08 APOPTOSIS 6.89e-07 1.23e-04 NOD1 2 SIGNALING PATHWAY 3.50e-06 5.61e-04 NFKB ACTIVATION THROUGH FADD RIP1 PATHWAY MEDIATED BY CASPASE 8 AND10 3.64e-06 5.81e-04 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 2.04e-05 2.91e-03 INNATE IMMUNE SYSTEM 8.51e-05 1.10e-02 APOPTOTIC CLEAVAGE OF CELLULAR PROTEINS 1.54e-04 1.87e-02 INTRINSIC PATHWAY FOR APOPTOSIS 1.95e-04 2.80e-02 NFKB ACTIVATION THROUGH FADD RIP1 PATHWAY MEDIATED BY CASPASE 8 AND10 1.98e-04 2.35e-02 APOPTOTIC EXECUTION PHASE 3.99e-04 4.43e-02 CASPASE MEDIATED CLEAVAGE OF CYTOSKELETAL PROTEINS 4.34e-04 5.68e-02 NOD1 2 SIGNALING PATHWAY 7.45e-04 7.71e-02 RIG I MDA5 MEDIATED INDUCTION OF IFN ALPHA BETA PATHWAYS 9.87e-04 1.17e-01 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 2.44e-03 2.52e-01 APOPTOTIC CLEAVAGE OF CELLULAR PROTEINS 3.45e-03 3.36e-01 CASPASE MEDIATED CLEAVAGE OF CYTOSKELETAL PROTEINS 4.38e-03 4.10e-01 APOPTOTIC EXECUTION PHASE 4.88e-03 4.49e-01 INTRINSIC PATHWAY FOR APOPTOSIS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.98e-06 2.00e-02 enlarged thymus 4.28e-05 1.29e-01 decreased susceptibility to endotoxin shock 1.74e-04 3.22e-01 increased cardiomyocyte apoptosis 3.77e-04 5.16e-01 decreased neuron apoptosis 4.34e-04 5.58e-01 decreased IgG level 4.48e-04 5.68e-01 decreased hepatocyte apoptosis 4.53e-04 5.71e-01 decreased sensitivity to induced cell death 4.59e-04 5.77e-01 abnormal negative T cell selection 6.73e-04 7.20e-01 decreased apoptosis 6.91e-04 7.31e-01 abnormal apoptosis 7.16e-04 7.46e-01 abnormal T cell physiology 8.08e-04 7.96e-01 decreased fibroblast apoptosis 9.12e-04 8.54e-01 decreased B cell apoptosis 1.28e-03 1.00e+00 increased IgA level 1.34e-03 1.00e+00 abnormal interleukin level 1.37e-03 1.00e+00 increased susceptibility to systemic lupus erythematosus 1.48e-03 1.00e+00 decreased physiological sensitivity to xenobiotic 1.50e-03 1.00e+00 abnormal airway responsiveness 1.59e-03 1.00e+00 increased IgG2a level 1.68e-03 1.00e+00 glomerular crescent

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

²FDR corrected p-value (Benjamini-Hochberg)