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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod149

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod149 Module size 40 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 51149 C5orf45 MRN complex interacting protein 929 CD14 CD14 molecule 4064 CD180 CD180 molecule 245812 CNPY4 canopy FGF signaling regulator 4 1673 DEFB4A defensin beta 4A 100289462 DEFB4B defensin beta 4B 300447 ECSIT ECSIT signalling integrator 5610 EIF2AK2 eukaryotic translation initiation factor 2 alpha kinase 2 3552 IL1A interleukin 1 alpha 3553 IL1B interleukin 1 beta 84639 IL1F10 interleukin 1 family member 10 3554 IL1R1 interleukin 1 receptor type 1 7850 IL1R2 interleukin 1 receptor type 2 3556 IL1RAP interleukin 1 receptor accessory protein 9173 IL1RL1 interleukin 1 receptor like 1 3557 IL1RN interleukin 1 receptor antagonist 3654 IRAK1 interleukin 1 receptor associated kinase 1 3656 IRAK2 interleukin 1 receptor associated kinase 2 11213 IRAK3 interleukin 1 receptor associated kinase 3 9450 LY86 lymphocyte antigen 86 23643 LY96 lymphocyte antigen 96 84935 MEDAG mesenteric estrogen dependent adipogenesis 4615 MYD88 MYD88, innate immune signal transduction adaptor 57162 PELI1 pellino E3 ubiquitin protein ligase 1 57161 PELI2 pellino E3 ubiquitin protein ligase family member 2 246330 PELI3 pellino E3 ubiquitin protein ligase family member 3 54476 RNF216 ring finger protein 216 6279 S100A8 S100 calcium binding protein A8 59307 SIGIRR single Ig and TIR domain containing 148022 TICAM1 toll like receptor adaptor molecule 1 353376 TICAM2 toll like receptor adaptor molecule 2 114609 TIRAP TIR domain containing adaptor protein 7096 TLR1 toll like receptor 1 7097 TLR2 toll like receptor 2 7098 TLR3 toll like receptor 3 7099 TLR4 toll like receptor 4 7100 TLR5 toll like receptor 5 10333 TLR6 toll like receptor 6 54472 TOLLIP toll interacting protein 85463 ZC3H12C zinc finger CCCH-type containing 12C

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 4.71e-01 4.77e-06 Reactome TICAM1 deficiency - HSE Disease 3.79e-01 4.28e-20 Reactome MyD88 deficiency (TLR2/4) Disease 2.95e-01 1.43e-05 Reactome Interleukin-33 signaling Immune System 1.33e-01 5.37e-27 GO interleukin-1-mediated signaling pathway biological_process 1.29e-01 2.85e-05 Reactome Interleukin-1 processing Immune System 1.20e-01 4.42e-03 Reactome Inhibition of PKR Disease 1.14e-01 1.43e-05 Reactome MyD88 deficiency (TLR5) Disease 1.14e-01 5.05e-12 Reactome TRIF-mediated programmed cell death Immune System 1.04e-01 9.95e-09 GO interleukin-1 receptor binding molecular_function 7.11e-02 1.63e-15 Reactome Regulation of TLR by endogenous ligand Immune System 3.98e-02 4.24e-09 Reactome IRAK1 recruits IKK complex Immune System 3.64e-02 4.24e-09 Reactome IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation Immune System 3.14e-02 3.55e-14 GO MyD88-independent toll-like receptor signaling pathway biological_process 3.06e-02 1.05e-24 GO MyD88-dependent toll-like receptor signaling pathway biological_process 2.94e-02 5.48e-11 GO response to interleukin-1 biological_process 2.55e-02 1.32e-04 GO negative regulation of cytokine-mediated signaling pathway biological_process 1.77e-02 9.42e-13 GO necroptotic process biological_process 1.60e-02 2.02e-21 GO toll-like receptor signaling pathway biological_process 1.18e-02 2.64e-15 GO lipopolysaccharide-mediated signaling pathway 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 inflammatory response 0e+00 0e+00 positive regulation of NF-kappaB transcription factor activity 0e+00 0e+00 response to molecule of bacterial origin 0e+00 0e+00 MyD88-dependent toll-like receptor signaling pathway 0e+00 0e+00 immune response-activating signal transduction 0e+00 0e+00 innate immune response-activating signal transduction 0e+00 0e+00 cellular response to molecule of bacterial origin 0e+00 0e+00 response to other organism 0e+00 0e+00 pattern recognition receptor signaling pathway 0e+00 0e+00 response to biotic stimulus 0e+00 0e+00 activation of innate immune response 0e+00 0e+00 toll-like receptor signaling pathway 0e+00 0e+00 response to bacterium 0e+00 0e+00 positive regulation of innate immune response 0e+00 0e+00 innate immune response 0e+00 0e+00 regulation of innate immune response 0e+00 0e+00 regulation of cytokine production 0e+00 0e+00 positive regulation of cytokine production 0e+00 0e+00 regulation of interleukin-6 production 0e+00 0e+00 regulation of toll-like receptor signaling pathway

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 SIGNALING BY ILS 0.00e+00 0.00e+00 ACTIVATED TLR4 SIGNALLING 0.00e+00 0.00e+00 TOLL RECEPTOR CASCADES 0.00e+00 0.00e+00 INNATE IMMUNE SYSTEM 0.00e+00 0.00e+00 MYD88 MAL CASCADE INITIATED ON PLASMA MEMBRANE 0.00e+00 0.00e+00 IL1 SIGNALING 0.00e+00 0.00e+00 SIGNALING BY ILS 0.00e+00 0.00e+00 TOLL RECEPTOR CASCADES 0.00e+00 0.00e+00 INNATE IMMUNE SYSTEM 0.00e+00 0.00e+00 MYD88 MAL CASCADE INITIATED ON PLASMA MEMBRANE 0.00e+00 0.00e+00 ACTIVATED TLR4 SIGNALLING 0.00e+00 0.00e+00 IL1 SIGNALING 1.21e-10 4.36e-08 IKK COMPLEX RECRUITMENT MEDIATED BY RIP1 1.50e-10 4.03e-08 CYTOKINE SIGNALING IN IMMUNE SYSTEM 1.92e-10 6.82e-08 CYTOKINE SIGNALING IN IMMUNE SYSTEM 5.83e-10 1.46e-07 IKK COMPLEX RECRUITMENT MEDIATED BY RIP1 8.74e-10 2.90e-07 TRAF6 MEDIATED INDUCTION OF TAK1 COMPLEX 1.19e-09 3.90e-07 ACTIVATION OF IRF3 IRF7 MEDIATED BY TBK1 IKK EPSILON 1.98e-09 4.66e-07 TRAF6 MEDIATED INDUCTION OF TAK1 COMPLEX 7.68e-09 1.71e-06 ACTIVATION OF IRF3 IRF7 MEDIATED BY TBK1 IKK EPSILON

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 0.00e+00 0.00e+00 decreased tumor necrosis factor secretion 0.00e+00 0.00e+00 abnormal macrophage physiology 0.00e+00 0.00e+00 decreased interleukin-6 secretion 4.83e-11 2.88e-06 decreased circulating interleukin-6 level 3.65e-10 1.62e-05 abnormal cytokine secretion 1.06e-07 1.49e-03 decreased interleukin-12b secretion 1.11e-07 1.52e-03 decreased circulating tumor necrosis factor level 1.11e-07 1.52e-03 abnormal dendritic cell physiology 1.20e-07 1.60e-03 decreased susceptibility to viral infection 2.71e-07 3.14e-03 decreased interleukin-1 beta secretion 3.57e-07 3.98e-03 increased susceptibility to bacterial infection 4.76e-07 5.04e-03 decreased macrophage cytokine production 6.33e-07 6.29e-03 decreased susceptibility to endotoxin shock 3.18e-06 2.08e-02 decreased interferon-alpha secretion 5.05e-06 2.95e-02 decreased susceptibility to kidney reperfusion injury 5.97e-06 3.24e-02 decreased susceptibility to viral infection induced morbidity/mortality 6.32e-06 3.39e-02 abnormal innate immunity 6.38e-06 3.40e-02 decreased B cell proliferation 1.04e-05 4.82e-02 abnormal tumor necrosis factor level 1.66e-05 6.68e-02 abnormal interleukin level

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

²FDR corrected p-value (Benjamini-Hochberg)