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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod283

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod283 Module size 44 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 79800 ALS2CR8 calcium responsive transcription factor 143384 CACUL1 CDK2 associated cullin domain 1 1029 CDKN2A cyclin dependent kinase inhibitor 2A 1030 CDKN2B cyclin dependent kinase inhibitor 2B 27013 CNPPD1 cyclin Pas1/PHO80 domain containing 1 53944 CSNK1G1 casein kinase 1 gamma 1 1456 CSNK1G3 casein kinase 1 gamma 3 1469 CST1 cystatin SN 8453 CUL2 cullin 2 55172 DNAAF2 dynein axonemal assembly factor 2 1979 EIF4EBP2 eukaryotic translation initiation factor 4E binding protein 2 8603 FAM193A family with sequence similarity 193 member A 55294 FBXW7 F-box and WD repeat domain containing 7 2977 GUCY1A2 guanylate cyclase 1 soluble subunit alpha 2 2982 GUCY1A3 guanylate cyclase 1 soluble subunit alpha 1 2983 GUCY1B3 guanylate cyclase 1 soluble subunit beta 1 55662 HIF1AN hypoxia inducible factor 1 subunit alpha inhibitor 5654 HTRA1 HtrA serine peptidase 1 27429 HTRA2 HtrA serine peptidase 2 94031 HTRA3 HtrA serine peptidase 3 203100 HTRA4 HtrA serine peptidase 4 9641 IKBKE inhibitor of nuclear factor kappa B kinase subunit epsilon 57534 MIB1 mindbomb E3 ubiquitin protein ligase 1 136319 MTPN myotrophin 4552 MTRR 5-methyltetrahydrofolate-homocysteine methyltransferase reductase 27158 NDOR1 NADPH dependent diflavin oxidoreductase 1 4791 NFKB2 nuclear factor kappa B subunit 2 4792 NFKBIA NFKB inhibitor alpha 4793 NFKBIB NFKB inhibitor beta 55768 NGLY1 N-glycanase 1 340719 NOS1 nanos C2HC-type zinc finger 1 4843 NOS2 nitric oxide synthase 2 342977 NOS3 nanos C2HC-type zinc finger 3 100360437 POR NOP2/Sun RNA methyltransferase family member 3 11317 RBPJL recombination signal binding protein for immunoglobulin kappa J region like 5966 REL REL proto-oncogene, NF-kB subunit 253260 RICTOR RPTOR independent companion of MTOR complex 2 9616 RNF7 ring finger protein 7 85461 TANC1 tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1 83940 TATDN1 TatD DNase domain containing 1 9797 TATDN2 TatD DNase domain containing 2 128387 TATDN3 TatD DNase domain containing 3 219743 TYSND1 trypsin domain containing 1 64718 UNKL unkempt family like zinc finger

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 7.06e-01 1.47e-16 GO NADPH-hemoprotein reductase activity molecular_function 7.63e-02 2.21e-06 Reactome SUMOylation of immune response proteins Metabolism of proteins 7.43e-02 2.21e-06 Reactome RIP-mediated NFkB activation via ZBP1 Immune System 4.55e-02 2.52e-11 Reactome Nitric oxide stimulates guanylate cyclase Hemostasis 2.92e-02 1.51e-05 GO insulin-like growth factor binding molecular_function 2.81e-02 7.32e-03 Reactome Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha Cellular responses to external stimuli 1.52e-02 9.03e-06 GO NIK/NF-kappaB signaling biological_process 1.32e-02 3.79e-04 GO cyclin-dependent protein serine/threonine kinase inhibitor activity molecular_function 1.20e-02 3.79e-04 GO cullin-RING ubiquitin ligase complex cellular_component

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 NADPH-hemoprotein reductase activity 1.50e-11 9.82e-09 FMN binding 1.93e-11 1.25e-08 oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor 1.26e-08 8.11e-06 positive regulation of cGMP biosynthetic process 1.62e-08 1.03e-05 nitric oxide mediated signal transduction 2.12e-08 1.32e-05 positive regulation of cGMP metabolic process 2.68e-08 1.65e-05 regulation of cGMP biosynthetic process 6.83e-08 2.69e-05 NADP binding 9.97e-08 5.63e-05 regulation of cGMP metabolic process 1.91e-07 6.98e-05 nitric-oxide synthase activity 5.85e-07 1.94e-04 tetrahydrobiopterin binding 6.22e-07 2.05e-04 flavin adenine dinucleotide binding 1.21e-06 3.49e-04 I-kappaB/NF-kappaB complex 1.66e-06 7.57e-04 nitric oxide metabolic process 2.06e-06 6.16e-04 oxidoreductase activity, acting on NAD(P)H 3.48e-06 1.49e-03 arginine catabolic process 3.67e-06 1.05e-03 arginine binding 1.01e-05 2.63e-03 heme binding 2.24e-05 7.94e-03 positive regulation of guanylate cyclase activity 2.85e-05 6.38e-03 guanylate cyclase complex, soluble

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.76e-10 4.70e-08 NITRIC OXIDE STIMULATES GUANYLATE CYCLASE 2.53e-09 7.88e-07 NITRIC OXIDE STIMULATES GUANYLATE CYCLASE 9.42e-07 1.64e-04 PLATELET HOMEOSTASIS 9.34e-06 1.80e-03 PLATELET HOMEOSTASIS 9.67e-05 1.50e-02 LATENT INFECTION OF HOMO SAPIENS WITH MYCOBACTERIUM TUBERCULOSIS 1.67e-04 2.02e-02 LATENT INFECTION OF HOMO SAPIENS WITH MYCOBACTERIUM TUBERCULOSIS 1.76e-04 2.11e-02 RIP MEDIATED NFKB ACTIVATION VIA DAI 2.28e-04 2.67e-02 TRAF6 MEDIATED NFKB ACTIVATION 3.14e-04 3.57e-02 RIG I MDA5 MEDIATED INDUCTION OF IFN ALPHA BETA PATHWAYS 3.66e-04 4.89e-02 RIP MEDIATED NFKB ACTIVATION VIA DAI 5.10e-04 5.53e-02 TAK1 ACTIVATES NFKB BY PHOSPHORYLATION AND ACTIVATION OF IKKS COMPLEX 6.01e-04 7.57e-02 TRAF6 MEDIATED NFKB ACTIVATION 1.12e-03 1.11e-01 TRIF MEDIATED TLR3 SIGNALING 1.15e-03 1.33e-01 TAK1 ACTIVATES NFKB BY PHOSPHORYLATION AND ACTIVATION OF IKKS COMPLEX 1.22e-03 1.39e-01 RIG I MDA5 MEDIATED INDUCTION OF IFN ALPHA BETA PATHWAYS 1.88e-03 1.76e-01 ACTIVATED TLR4 SIGNALLING 2.94e-03 2.61e-01 DOWNSTREAM SIGNALING EVENTS OF B CELL RECEPTOR BCR 3.20e-03 2.81e-01 TOLL RECEPTOR CASCADES 3.65e-03 3.52e-01 TRIF MEDIATED TLR3 SIGNALING 4.65e-03 3.87e-01 REGULATION OF HYPOXIA INDUCIBLE FACTOR HIF BY OXYGEN

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.91e-05 1.00e-01 abnormal heart right ventricle pressure 2.15e-04 3.64e-01 abnormal blood circulation 3.38e-04 4.82e-01 abnormal vasodilation 4.08e-04 5.37e-01 decreased coronary flow rate 5.85e-04 6.66e-01 increased systemic arterial systolic blood pressure 6.04e-04 6.78e-01 pericardial edema 7.46e-04 7.62e-01 abnormal seizure response to inducing agent 7.61e-04 7.67e-01 spleen atrophy 8.38e-04 8.15e-01 increased tidal volume 1.25e-03 1.00e+00 abnormal systemic arterial blood pressure 1.55e-03 1.00e+00 extramedullary hematopoiesis 1.68e-03 1.00e+00 increased double-positive T cell number 1.93e-03 1.00e+00 increased urine pH 2.15e-03 1.00e+00 increased systemic arterial blood pressure 2.26e-03 1.00e+00 abnormal platelet aggregation 2.37e-03 1.00e+00 decreased transitional stage T2 B cell number 2.51e-03 1.00e+00 decreased B-2 B cell number 2.52e-03 1.00e+00 decreased adiponectin level 2.65e-03 1.00e+00 decreased fertilization frequency 3.18e-03 1.00e+00 decreased susceptibility to induced choroidal neovascularization

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

²FDR corrected p-value (Benjamini-Hochberg)