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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod255

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod255 Module size 52 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 64343 AZI2 5-azacytidine induced 2 83636 C19orf12 chromosome 19 open reading frame 12 56911 C21orf7 MAP3K7 C-terminal like 84433 CARD11 caspase recruitment domain family member 11 64170 CARD9 caspase recruitment domain family member 9 149473 CCDC24 coiled-coil domain containing 24 152137 CCDC50 coiled-coil domain containing 50 1147 CHUK conserved helix-loop-helix ubiquitous kinase 1540 CYLD CYLD lysine 63 deubiquitinase 60401 EDA2R ectodysplasin A2 receptor 100820829 GCOM1 myocardial zonula adherens protein 3551 IKBKB inhibitor of nuclear factor kappa B kinase subunit beta 8517 IKBKG inhibitor of nuclear factor kappa B kinase subunit gamma 134728 IRAK1BP1 interleukin 1 receptor associated kinase 1 binding protein 1 57577 KIAA1407 coiled-coil domain containing 191 10892 MALT1 MALT1 paracaspase 57506 MAVS mitochondrial antiviral signaling protein 64112 MOAP1 modulator of apoptosis 1 4790 NFKB1 nuclear factor kappa B subunit 1 57185 NIPAL3 NIPA like domain containing 3 147945 NLRP4 NLR family pyrin domain containing 4 79671 NLRX1 NLR family member X1 56957 OTUD7B OTU deubiquitinase 7B 23241 PACS2 phosphofurin acidic cluster sorting protein 2 27143 PALD1 phosphatase domain containing, paladin 1 5920 RARRES3 retinoic acid receptor responder 3 5970 RELA RELA proto-oncogene, NF-kB subunit 55072 RNF31 ring finger protein 31 81858 SHARPIN SHANK associated RH domain interactor 124044 SPATA2L spermatogenesis associated 2 like 727830 SPATA31A3 SPATA31 subfamily A member 3 23118 TAB2 TGF-beta activated kinase 1 (MAP3K7) binding protein 2 257397 TAB3 TGF-beta activated kinase 1 (MAP3K7) binding protein 3 10010 TANK TRAF family member associated NFKB activator 8887 TAX1BP1 Tax1 binding protein 1 29110 TBK1 TANK binding kinase 1 9755 TBKBP1 TBK1 binding protein 1 51567 TDP2 tyrosyl-DNA phosphodiesterase 2 7128 TNFAIP3 TNF alpha induced protein 3 8600 TNFSF11 TNF superfamily member 11 407977 TNFSF12-TNFSF13 TNFSF12-TNFSF13 readthrough 23043 TNIK TRAF2 and NCK interacting kinase 10318 TNIP1 TNFAIP3 interacting protein 1 79155 TNIP2 TNFAIP3 interacting protein 2 79931 TNIP3 TNFAIP3 interacting protein 3 9618 TRAF4 TNF receptor associated factor 4 7189 TRAF6 TNF receptor associated factor 6 4591 TRIM37 tripartite motif containing 37 89891 WDR34 WD repeat domain 34 81030 ZBP1 Z-DNA binding protein 1 80149 ZC3H12A zinc finger CCCH-type containing 12A 7763 ZFAND5 zinc finger AN1-type containing 5

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 2.32e-01 2.10e-05 GO protein linear polyubiquitination biological_process 2.20e-01 2.10e-05 Reactome IRF3 mediated activation of type 1 IFN Immune System 1.86e-01 2.30e-12 Reactome IkBA variant leads to EDA-ID Disease 1.52e-01 1.80e-08 Reactome IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) Disease 8.75e-02 1.23e-28 GO I-kappaB kinase/NF-kappaB signaling biological_process 6.41e-02 5.95e-17 Reactome NOD1/2 Signaling Pathway Immune System 5.35e-02 1.54e-11 GO negative regulation of I-kappaB kinase/NF-kappaB signaling biological_process 4.98e-02 1.04e-15 Reactome ZBP1(DAI) mediated induction of type I IFNs Immune System 4.61e-02 1.19e-10 GO negative regulation of type I interferon production biological_process 4.49e-02 6.88e-15 Reactome TRAF6 mediated NF-kB activation Immune System 3.89e-02 2.80e-09 GO K63-linked polyubiquitin modification-dependent protein binding molecular_function 3.80e-02 9.37e-18 GO stimulatory C-type lectin receptor signaling pathway biological_process 3.24e-02 6.41e-14 Reactome Ovarian tumor domain proteases Metabolism of proteins 2.95e-02 2.10e-08 GO tumor necrosis factor receptor binding molecular_function 2.74e-02 1.74e-19 Reactome TNF signaling Signal Transduction 1.44e-02 2.92e-06 Reactome Regulated proteolysis of p75NTR Signal Transduction 1.31e-02 3.89e-06 GO regulation of type I interferon production biological_process 6.57e-03 1.60e-21 Reactome DDX58/IFIH1-mediated induction of interferon-alpha/beta Immune System 5.81e-03 1.71e-16 Reactome TAK1 activates NFkB by phosphorylation and activation of IKKs complex Immune System

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 I-kappaB kinase/NF-kappaB signaling 0.00e+00 0.00e+00 regulation of I-kappaB kinase/NF-kappaB signaling 0.00e+00 0.00e+00 pattern recognition receptor signaling pathway 0.00e+00 0.00e+00 activation of innate immune response 0.00e+00 0.00e+00 immune response-activating signal transduction 0.00e+00 0.00e+00 innate immune response-activating signal transduction 0.00e+00 0.00e+00 positive regulation of immune response 0.00e+00 0.00e+00 immune response-regulating signaling pathway 0.00e+00 0.00e+00 positive regulation of innate immune response 0.00e+00 0.00e+00 regulation of innate immune response 0.00e+00 0.00e+00 positive regulation of I-kappaB kinase/NF-kappaB signaling 0.00e+00 0.00e+00 positive regulation of sequence-specific DNA binding transcription factor activity 0.00e+00 0.00e+00 positive regulation of NF-kappaB transcription factor activity 0.00e+00 0.00e+00 regulation of sequence-specific DNA binding transcription factor activity 0.00e+00 0.00e+00 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway 0.00e+00 0.00e+00 nucleotide-binding oligomerization domain containing signaling pathway 1.95e-11 1.73e-08 toll-like receptor signaling pathway 3.39e-10 1.95e-07 polyubiquitin binding 8.65e-10 6.49e-07 regulation of type I interferon production 1.14e-09 8.43e-07 stress-activated MAPK cascade

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 NOD1 2 SIGNALING PATHWAY 0.00e+00 0.00e+00 INNATE IMMUNE SYSTEM 0.00e+00 0.00e+00 RIG I MDA5 MEDIATED INDUCTION OF IFN ALPHA BETA PATHWAYS 0.00e+00 0.00e+00 NOD1 2 SIGNALING PATHWAY 0.00e+00 0.00e+00 INNATE IMMUNE SYSTEM 0.00e+00 0.00e+00 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 0.00e+00 0.00e+00 RIG I MDA5 MEDIATED INDUCTION OF IFN ALPHA BETA PATHWAYS 4.98e-12 1.93e-09 NUCLEOTIDE BINDING DOMAIN LEUCINE RICH REPEAT CONTAINING RECEPTOR NLR SIGNALING PATHWAYS 6.08e-10 1.52e-07 DOWNSTREAM TCR SIGNALING 9.43e-10 3.12e-07 DOWNSTREAM TCR SIGNALING 1.12e-09 3.68e-07 TAK1 ACTIVATES NFKB BY PHOSPHORYLATION AND ACTIVATION OF IKKS COMPLEX 3.20e-09 9.84e-07 NEGATIVE REGULATORS OF RIG I MDA5 SIGNALING 3.21e-09 7.41e-07 TAK1 ACTIVATES NFKB BY PHOSPHORYLATION AND ACTIVATION OF IKKS COMPLEX 3.69e-09 8.46e-07 TCR SIGNALING 1.09e-08 3.18e-06 TCR SIGNALING 1.28e-08 2.78e-06 NEGATIVE REGULATORS OF RIG I MDA5 SIGNALING 1.51e-08 4.32e-06 TRIF MEDIATED TLR3 SIGNALING 1.54e-08 4.40e-06 TRAF6 MEDIATED NFKB ACTIVATION 1.81e-08 5.12e-06 IL1 SIGNALING 1.86e-08 3.96e-06 TRAF6 MEDIATED NFKB ACTIVATION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.56e-09 5.08e-05 decreased interleukin-6 secretion 3.35e-07 3.80e-03 increased IgA level 5.53e-07 5.68e-03 abnormal dendritic cell physiology 7.24e-06 3.70e-02 increased interleukin-6 secretion 9.51e-06 4.56e-02 skin inflammation 1.53e-05 6.28e-02 increased IgG2a level 1.86e-05 7.20e-02 decreased interleukin-12b secretion 2.60e-05 9.35e-02 abnormal macrophage physiology 3.99e-05 1.23e-01 decreased tumor necrosis factor secretion 4.28e-05 1.29e-01 liver hemorrhage 5.01e-05 1.43e-01 enlarged spleen 1.02e-04 2.29e-01 abnormal B cell physiology 1.55e-04 3.01e-01 increased IgM level 2.48e-04 3.97e-01 increased IgG1 level 2.61e-04 4.11e-01 increased IgG2b level 3.25e-04 4.72e-01 increased hepatocyte apoptosis 3.77e-04 5.16e-01 increased keratinocyte proliferation 3.87e-04 5.22e-01 decreased B cell proliferation 3.91e-04 5.24e-01 abnormal chemokine secretion 4.63e-04 5.80e-01 lung inflammation

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

²FDR corrected p-value (Benjamini-Hochberg)