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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod50

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod50 Module size 52 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 9447 AIM2 absent in melanoma 2 57099 AVEN apoptosis and caspase activation inhibitor 572 BAD BCL2 associated agonist of cell death 578 BAK1 BCL2 antagonist/killer 1 581 BAX BCL2 associated X, apoptosis regulator 27113 BBC3 BCL2 binding component 3 596 BCL2 BCL2, apoptosis regulator 597 BCL2A1 BCL2 related protein A1 598 BCL2L1 BCL2 like 1 10017 BCL2L10 BCL2 like 10 10018 BCL2L11 BCL2 like 11 638 BIK BCL2 interacting killer 79444 BIRC7 baculoviral IAP repeat containing 7 112401 BIRC8 baculoviral IAP repeat containing 8 414899 BLID BH3-like motif containing, cell death inducer 90427 BMF Bcl2 modifying factor 54796 BNC2 basonuclin 2 64073 C19orf33 chromosome 19 open reading frame 33 114769 CARD16 caspase recruitment domain family member 16 440068 CARD17 caspase recruitment domain family member 17 59082 CARD18 caspase recruitment domain family member 18 84674 CARD6 caspase recruitment domain family member 6 22900 CARD8 caspase recruitment domain family member 8 834 CASP1 caspase 1 100506742 CASP12 caspase 12 (gene/pseudogene) 23581 CASP14 caspase 14 197350 CASP16 caspase 16, pseudogene 837 CASP4 caspase 4 838 CASP5 caspase 5 839 CASP6 caspase 6 840 CASP7 caspase 7 842 CASP9 caspase 9 1149 CIDEA cell death-inducing DFFA-like effector a 56616 DIABLO diablo IAP-binding mitochondrial protein 653519 GPR89A G protein-coupled receptor 89A 653519 GPR89B G protein-coupled receptor 89A 51463 GPR89C G protein-coupled receptor 89B 8739 HRK harakiri, BCL2 interacting protein 4170 MCL1 MCL1, BCL2 family apoptosis regulator 4671 NAIP NLR family apoptosis inhibitory protein 375607 NAT16 N-acetyltransferase 16 (putative) 58484 NLRC4 NLR family CARD domain containing 4 22861 NLRP1 NLR family pyrin domain containing 1 114548 NLRP3 NLR family pyrin domain containing 3 10392 NOD1 nucleotide binding oligomerization domain containing 1 64127 NOD2 nucleotide binding oligomerization domain containing 2 10562 OLFM4 olfactomedin 4 5366 PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 29108 PYCARD PYD and CARD domain containing 23098 SARM1 sterile alpha and TIR motif containing 1 128497 SPATA25 spermatogenesis associated 25 331 XIAP X-linked inhibitor of apoptosis

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 4.08e-01 4.89e-18 Reactome BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members Programmed Cell Death 2.77e-01 1.80e-08 Reactome The AIM2 inflammasome Immune System 2.54e-01 1.52e-20 GO cysteine-type endopeptidase activity involved in apoptotic process molecular_function 2.42e-01 1.80e-08 Reactome The NLRP1 inflammasome Immune System 2.04e-01 2.07e-15 GO CARD domain binding molecular_function 1.36e-01 1.39e-10 GO negative regulation of interleukin-1 beta secretion biological_process 1.19e-01 2.25e-10 Reactome SMAC-mediated dissociation of IAP:caspase complexes Programmed Cell Death 1.17e-01 2.25e-10 Reactome SMAC-mediated apoptotic response Programmed Cell Death 1.12e-01 2.25e-10 Reactome SMAC binds to IAPs Programmed Cell Death 1.11e-01 1.05e-04 GO voltage-gated anion channel activity molecular_function 1.04e-01 9.97e-07 GO detection of bacterium biological_process 8.94e-02 1.28e-19 GO positive regulation of release of cytochrome c from mitochondria biological_process 7.20e-02 2.76e-16 Reactome Inflammasomes Immune System 7.10e-02 1.47e-08 GO caspase binding molecular_function 5.70e-02 5.62e-09 GO positive regulation of protein homooligomerization biological_process 5.52e-02 1.92e-19 GO extrinsic apoptotic signaling pathway in absence of ligand biological_process 5.04e-02 7.68e-22 GO intrinsic apoptotic signaling pathway in response to DNA damage biological_process 3.72e-02 1.49e-06 GO positive regulation of interleukin-1 beta production biological_process 2.50e-02 2.08e-26 GO activation of cysteine-type endopeptidase activity involved in apoptotic process biological_process 1.82e-02 3.84e-07 GO cysteine-type endopeptidase inhibitor activity molecular_function 1.65e-02 1.95e-24 Reactome Intrinsic Pathway for Apoptosis Programmed Cell Death 1.05e-02 2.84e-13 GO positive regulation of interleukin-1 beta secretion biological_process 6.40e-03 2.54e-15 GO positive regulation of cysteine-type endopeptidase activity involved in apoptotic process biological_process 4.22e-05 3.07e-05 GO cysteine-type endopeptidase inhibitor activity involved in apoptotic process 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 0e+00 0e+00 apoptotic mitochondrial changes 0e+00 0e+00 positive regulation of release of cytochrome c from mitochondria 0e+00 0e+00 regulation of cysteine-type endopeptidase activity 0e+00 0e+00 positive regulation of cysteine-type endopeptidase activity 0e+00 0e+00 positive regulation of peptidase activity 0e+00 0e+00 positive regulation of endopeptidase activity 0e+00 0e+00 positive regulation of interleukin-1 beta production 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 intrinsic apoptotic signaling pathway 0e+00 0e+00 execution phase of apoptosis 0e+00 0e+00 AIM2 inflammasome complex 0e+00 0e+00 inflammasome complex 0e+00 0e+00 NLRP3 inflammasome complex 0e+00 0e+00 BH domain binding 0e+00 0e+00 cysteine-type endopeptidase regulator activity involved in apoptotic process 0e+00 0e+00 cysteine-type endopeptidase activity involved in execution phase of apoptosis 0e+00 0e+00 cysteine-type endopeptidase activity 0e+00 0e+00 cysteine-type endopeptidase activity involved in apoptotic process

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 APOPTOSIS 0.00e+00 0.00e+00 INTRINSIC PATHWAY FOR APOPTOSIS 0.00e+00 0.00e+00 INFLAMMASOMES 0.00e+00 0.00e+00 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 0.00e+00 0.00e+00 APOPTOSIS 0.00e+00 0.00e+00 INTRINSIC PATHWAY FOR APOPTOSIS 0.00e+00 0.00e+00 INFLAMMASOMES 0.00e+00 0.00e+00 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 1.45e-10 3.90e-08 ACTIVATION OF BH3 ONLY PROTEINS 5.67e-10 1.43e-07 INNATE IMMUNE SYSTEM 2.48e-09 7.74e-07 ACTIVATION OF BH3 ONLY PROTEINS 1.69e-08 4.79e-06 INNATE IMMUNE SYSTEM 9.14e-07 1.60e-04 NOD1 2 SIGNALING PATHWAY 1.02e-05 1.95e-03 NOD1 2 SIGNALING PATHWAY 1.69e-05 2.44e-03 THE NLRP3 INFLAMMASOME 3.20e-05 5.59e-03 THE NLRP3 INFLAMMASOME 1.40e-03 1.36e-01 CASPASE MEDIATED CLEAVAGE OF CYTOSKELETAL PROTEINS 3.14e-03 2.77e-01 AKT PHOSPHORYLATES TARGETS IN THE CYTOSOL 3.62e-03 3.50e-01 CASPASE MEDIATED CLEAVAGE OF CYTOSKELETAL PROTEINS 5.28e-03 4.30e-01 JNK C JUN KINASES PHOSPHORYLATION AND ACTIVATION MEDIATED BY ACTIVATED HUMAN TAK1

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.04e-09 3.80e-05 decreased interleukin-1 beta secretion 3.90e-08 6.78e-04 decreased circulating interleukin-18 level 7.44e-07 7.10e-03 decreased apoptosis 8.08e-07 7.36e-03 decreased interleukin-1 alpha secretion 3.15e-06 2.07e-02 decreased lactate dehydrogenase level 7.14e-06 3.69e-02 abnormal sympathetic neuron morphology 9.78e-06 4.66e-02 abnormal macrophage physiology 1.52e-05 6.25e-02 abnormal response to infection 6.64e-05 1.72e-01 decreased T cell apoptosis 7.97e-05 1.95e-01 decreased circulating interleukin-1 beta level 1.72e-04 3.20e-01 increased mature B cell number 1.77e-04 3.24e-01 decreased susceptibility to endotoxin shock 1.84e-04 3.31e-01 abnormal apoptosis 1.92e-04 3.40e-01 increased immature B cell number 2.36e-04 3.88e-01 increased interferon-beta secretion 2.46e-04 3.97e-01 decreased interleukin-18 secretion 2.77e-04 4.29e-01 abnormal CD8-positive, alpha-beta T cell physiology 3.44e-04 4.86e-01 increased circulating interleukin-3 level 3.45e-04 4.86e-01 abnormal CD4-positive, alpha beta T cell number 5.71e-04 6.58e-01 abnormal cytokine secretion

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

²FDR corrected p-value (Benjamini-Hochberg)