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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod88

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod88 Module size 39 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 1129 CHRM2 cholinergic receptor muscarinic 2 56144 CNR1 protocadherin alpha 4 1325 CORT cortistatin 2919 CXCL1 C-X-C motif chemokine ligand 1 3627 CXCL10 C-X-C motif chemokine ligand 10 6373 CXCL11 C-X-C motif chemokine ligand 11 6387 CXCL12 C-X-C motif chemokine ligand 12 2920 CXCL2 C-X-C motif chemokine ligand 2 4283 CXCL9 C-X-C motif chemokine ligand 9 3577 CXCR1 C-X-C motif chemokine receptor 1 10663 CXCR6 C-X-C motif chemokine receptor 6 57007 CXCR7 atypical chemokine receptor 3 1813 DRD2 dopamine receptor D2 1814 DRD3 dopamine receptor D3 1815 DRD4 dopamine receptor D4 2357 FPR1 formyl peptide receptor 1 51083 GAL galanin and GMAP prepropeptide 2914 GRM4 glutamate metabotropic receptor 4 2917 GRM7 glutamate metabotropic receptor 7 3350 HTR1A 5-hydroxytryptamine receptor 1A 116637 IL8 C-C motif chemokine ligand 4 4543 MTNR1A melatonin receptor 1A 4544 MTNR1B melatonin receptor 1B 4988 OPRM1 opioid receptor mu 1 5443 POMC proopiomelanocortin 5540 PPYR1 neuropeptide Y receptor Y4 5697 PYY peptide YY 5996 RGS1 regulator of G protein signaling 1 6001 RGS10 regulator of G protein signaling 10 10636 RGS14 regulator of G protein signaling 14 8601 RGS20 regulator of G protein signaling 20 5999 RGS4 regulator of G protein signaling 4 9628 RGS6 regulator of G protein signaling 6 6000 RGS7 regulator of G protein signaling 7 117579 RLN3 relaxin 3 51289 RXFP3 relaxin family peptide receptor 3 1901 S1PR1 sphingosine-1-phosphate receptor 1 8698 S1PR4 sphingosine-1-phosphate receptor 4 6753 SSTR3 somatostatin receptor 3

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 2.17e-01 9.17e-08 Reactome Dopamine receptors Signal Transduction 8.75e-02 8.54e-12 GO leukocyte chemotaxis biological_process 8.28e-02 4.30e-03 Reactome Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD) Disease 7.42e-02 5.11e-07 GO dopamine neurotransmitter receptor activity, coupled via Gi/Go molecular_function 6.47e-02 6.95e-10 GO G-protein alpha-subunit binding molecular_function 6.03e-02 9.42e-05 GO adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway biological_process 4.86e-02 2.38e-10 GO regulation of G-protein coupled receptor protein signaling pathway biological_process 2.72e-02 1.25e-04 Reactome Relaxin receptors Signal Transduction 2.64e-02 4.68e-42 Reactome G alpha (i) signalling events Signal Transduction 2.17e-02 4.80e-09 GO response to cocaine biological_process 2.17e-02 2.73e-39 Reactome Class A/1 (Rhodopsin-like receptors) Signal Transduction 1.55e-02 7.31e-14 Reactome Chemokine receptors bind chemokines Signal Transduction 1.20e-02 9.54e-13 GO G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger biological_process 8.90e-03 2.00e-06 GO negative regulation of protein secretion biological_process 5.93e-03 6.13e-06 GO positive regulation of cAMP-mediated signaling biological_process 3.49e-03 5.03e-08 Reactome Interleukin-10 signaling Immune System 1.92e-03 5.16e-14 GO chemotaxis 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 0.00e+00 0.00e+00 adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway 0.00e+00 0.00e+00 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger 0.00e+00 0.00e+00 adenylate cyclase-modulating G-protein coupled receptor signaling pathway 0.00e+00 0.00e+00 G-protein coupled receptor binding 0.00e+00 0.00e+00 G-protein coupled receptor activity 7.56e-12 5.07e-09 CXCR chemokine receptor binding 1.72e-10 1.40e-07 chemokine-mediated signaling pathway 1.04e-08 4.73e-06 G-protein alpha-subunit binding 1.47e-08 6.56e-06 chemokine activity 5.30e-08 2.12e-05 chemokine receptor binding 1.64e-07 8.93e-05 regulation of cAMP metabolic process 2.00e-07 7.29e-05 G-protein coupled peptide receptor activity 2.06e-07 1.10e-04 cell chemotaxis 4.23e-07 1.44e-04 CXCR3 chemokine receptor binding 4.32e-07 2.19e-04 regulation of G-protein coupled receptor protein signaling pathway 5.67e-07 2.82e-04 neuropeptide signaling pathway 5.91e-07 1.95e-04 dopamine neurotransmitter receptor activity, coupled via Gi/Go 1.19e-06 5.57e-04 chemical synaptic transmission 1.34e-06 6.22e-04 negative regulation of cAMP biosynthetic process 1.49e-06 6.86e-04 behavior

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 G ALPHA I SIGNALLING EVENTS 0.00e+00 0.00e+00 CHEMOKINE RECEPTORS BIND CHEMOKINES 0.00e+00 0.00e+00 CLASS A1 RHODOPSIN LIKE RECEPTORS 0.00e+00 0.00e+00 GPCR LIGAND BINDING 0.00e+00 0.00e+00 PEPTIDE LIGAND BINDING RECEPTORS 0.00e+00 0.00e+00 G ALPHA I SIGNALLING EVENTS 0.00e+00 0.00e+00 CHEMOKINE RECEPTORS BIND CHEMOKINES 0.00e+00 0.00e+00 PEPTIDE LIGAND BINDING RECEPTORS 1.48e-04 1.81e-02 AMINE LIGAND BINDING RECEPTORS 1.81e-04 2.63e-02 AMINE LIGAND BINDING RECEPTORS 1.06e-03 1.06e-01 G PROTEIN ACTIVATION 1.20e-03 1.38e-01 CLASS C 3 METABOTROPIC GLUTAMATE PHEROMONE RECEPTORS 5.25e-03 4.76e-01 G PROTEIN ACTIVATION 5.56e-03 4.47e-01 G ALPHA Z SIGNALLING EVENTS 1.19e-02 9.15e-01 G ALPHA Z SIGNALLING EVENTS 1.32e-02 9.18e-01 CLASS C 3 METABOTROPIC GLUTAMATE PHEROMONE RECEPTORS 1.47e-02 1.00e+00 OPIOID SIGNALLING 2.67e-02 1.00e+00 ENDOGENOUS STEROLS 3.42e-02 1.00e+00 OPIOID SIGNALLING 4.24e-02 1.00e+00 ACTIVATION OF GENES BY ATF4

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.19e-09 4.17e-05 impaired conditioned place preference behavior 1.25e-07 1.66e-03 impaired behavioral response to morphine 1.11e-05 5.09e-02 hypoactivity 2.39e-05 8.79e-02 abnormal behavioral response to addictive substance 3.30e-05 1.09e-01 abnormal operant conditioning behavior 4.43e-05 1.31e-01 increased susceptibility to pharmacologically induced seizures 4.61e-05 1.35e-01 increased total body fat amount 5.71e-05 1.56e-01 impaired behavioral response to addictive substance 7.23e-05 1.82e-01 increased behavioral withdrawal response 7.62e-05 1.89e-01 increased circulating adrenocorticotropin level 9.10e-05 2.12e-01 abnormal touch/ nociception 9.90e-05 2.25e-01 decreased chemically-elicited antinociception 1.10e-04 2.40e-01 increased susceptibility to neuronal excitotoxicity 2.82e-04 4.35e-01 decreased behavioral withdrawal response 3.43e-04 4.86e-01 hyperactivity elicited by ethanol administration 4.36e-04 5.60e-01 impaired behavioral response to xenobiotic 5.17e-04 6.19e-01 catalepsy 5.81e-04 6.63e-01 increased dopamine level 6.70e-04 7.20e-01 abnormal neuron physiology 7.53e-04 7.64e-01 increased chemically-elicited antinociception

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

²FDR corrected p-value (Benjamini-Hochberg)