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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod70

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod70 Module size 48 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 116 ADCYAP1 adenylate cyclase activating polypeptide 1 117 ADCYAP1R1 ADCYAP receptor type I 133 ADM adrenomedullin 79924 ADM2 adrenomedullin 2 135 ADORA2A adenosine A2a receptor 136 ADORA2B adenosine A2b receptor 153 ADRB1 adrenoceptor beta 1 155 ADRB3 adrenoceptor beta 3 797 CALCB calcitonin related polypeptide beta 799 CALCR calcitonin receptor 1392 CRH corticotropin releasing hormone 1395 CRHR2 corticotropin releasing hormone receptor 2 1812 DRD1 dopamine receptor D1 1816 DRD5 dopamine receptor D5 2492 FSHR follicle stimulating hormone receptor 2691 GHRH growth hormone releasing hormone 2692 GHRHR growth hormone releasing hormone receptor 114897 GIP C1q and TNF related 1 2696 GIPR gastric inhibitory polypeptide receptor 2740 GLP1R glucagon like peptide 1 receptor 9340 GLP2R glucagon like peptide 2 receptor 151306 GPBAR1 G protein-coupled bile acid receptor 1 1665 HRH2 DEAH-box helicase 15 3360 HTR4 5-hydroxytryptamine receptor 4 3362 HTR6 5-hydroxytryptamine receptor 6 3363 HTR7 5-hydroxytryptamine receptor 7 3375 IAPP islet amyloid polypeptide 3973 LHCGR luteinizing hormone/choriogonadotropin receptor 4157 MC1R melanocortin 1 receptor 4158 MC2R melanocortin 2 receptor 4159 MC3R melanocortin 3 receptor 4160 MC4R melanocortin 4 receptor 4161 MC5R melanocortin 5 receptor 5729 PTGDR prostaglandin D2 receptor 5732 PTGER2 prostaglandin E receptor 2 5734 PTGER4 prostaglandin E receptor 4 5739 PTGIR prostaglandin I2 receptor 5741 PTH parathyroid hormone 5745 PTH1R parathyroid hormone 1 receptor 298861 PTH2 peptidyl-tRNA hydrolase domain containing 1 5746 PTH2R parathyroid hormone 2 receptor 5744 PTHLH parathyroid hormone like hormone 2317 SCT filamin B 134864 TAAR1 trace amine associated receptor 1 7253 TSHR thyroid stimulating hormone receptor 27151 VIP C3 and PZP like, alpha-2-macroglobulin domain containing 8 7433 VIPR1 vasoactive intestinal peptide receptor 1 7434 VIPR2 vasoactive intestinal peptide receptor 2

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 1.72e-01 3.43e-11 GO peptide hormone receptor binding molecular_function 1.63e-01 6.69e-09 Reactome Prostanoid ligand receptors Signal Transduction 1.57e-01 9.91e-29 GO activation of adenylate cyclase activity biological_process 1.11e-01 3.43e-11 Reactome Calcitonin-like ligand receptors Signal Transduction 9.93e-02 2.04e-07 Reactome NGF-independant TRKA activation Signal Transduction 9.58e-02 1.60e-14 GO positive regulation of cAMP-mediated signaling biological_process 9.19e-02 8.16e-26 GO G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger biological_process 8.37e-02 1.98e-49 GO adenylate cyclase-activating G-protein coupled receptor signaling pathway biological_process 8.25e-02 2.55e-43 Reactome Class B/2 (Secretin family receptors) Signal Transduction 6.72e-02 8.24e-25 GO G-protein coupled peptide receptor activity molecular_function 6.62e-02 3.79e-22 GO peptide hormone binding molecular_function 6.46e-02 1.73e-23 Reactome Glucagon-type ligand receptors Signal Transduction 6.43e-02 4.57e-05 Reactome Adenosine P1 receptors Signal Transduction 4.30e-02 5.26e-08 GO synaptic transmission, dopaminergic biological_process 3.55e-02 2.47e-15 Reactome Amine ligand-binding receptors Signal Transduction 2.39e-02 5.32e-73 Reactome G alpha (s) signalling events Signal Transduction 1.63e-02 5.58e-03 Reactome Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD) Disease 2.63e-03 1.66e-77 Reactome GPCR ligand binding Signal Transduction

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 positive regulation of cyclase activity 0.00e+00 0.00e+00 positive regulation of adenylate cyclase activity 0.00e+00 0.00e+00 regulation of cyclase activity 0.00e+00 0.00e+00 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger 0.00e+00 0.00e+00 positive regulation of cAMP biosynthetic process 0.00e+00 0.00e+00 adenylate cyclase-modulating G-protein coupled receptor signaling pathway 0.00e+00 0.00e+00 adenylate cyclase-activating G-protein coupled receptor signaling pathway 0.00e+00 0.00e+00 regulation of cAMP metabolic process 0.00e+00 0.00e+00 regulation of cAMP biosynthetic process 0.00e+00 0.00e+00 positive regulation of cAMP metabolic process 0.00e+00 0.00e+00 positive regulation of cyclic nucleotide metabolic process 0.00e+00 0.00e+00 positive regulation of lyase activity 0.00e+00 0.00e+00 activation of adenylate cyclase activity 0.00e+00 0.00e+00 regulation of adenylate cyclase activity 0.00e+00 0.00e+00 G-protein coupled receptor activity 0.00e+00 0.00e+00 G-protein coupled peptide receptor activity 0.00e+00 0.00e+00 hormone activity 3.20e-12 2.18e-09 melanocortin receptor activity 8.94e-11 5.48e-08 hormone binding 3.14e-10 2.48e-07 regulation of adenylate cyclase activity involved in G-protein coupled 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 G ALPHA S SIGNALLING EVENTS 0.00e+00 0.00e+00 GPCR LIGAND BINDING 0.00e+00 0.00e+00 CLASS B 2 SECRETIN FAMILY RECEPTORS 0.00e+00 0.00e+00 GLUCAGON TYPE LIGAND RECEPTORS 0.00e+00 0.00e+00 G ALPHA S SIGNALLING EVENTS 0.00e+00 0.00e+00 CLASS B 2 SECRETIN FAMILY RECEPTORS 0.00e+00 0.00e+00 GLUCAGON TYPE LIGAND RECEPTORS 2.50e-15 9.87e-13 CLASS A1 RHODOPSIN LIKE RECEPTORS 8.50e-10 2.83e-07 AMINE LIGAND BINDING RECEPTORS 1.16e-09 2.80e-07 AMINE LIGAND BINDING RECEPTORS 2.02e-07 3.81e-05 PROSTANOID LIGAND RECEPTORS 1.61e-06 3.50e-04 PROSTANOID LIGAND RECEPTORS 8.11e-06 1.23e-03 EICOSANOID LIGAND BINDING RECEPTORS 4.07e-05 6.96e-03 EICOSANOID LIGAND BINDING RECEPTORS 1.50e-04 1.83e-02 SEROTONIN RECEPTORS 1.87e-04 2.70e-02 HORMONE LIGAND BINDING RECEPTORS 2.11e-04 2.49e-02 HORMONE LIGAND BINDING RECEPTORS 3.17e-04 3.60e-02 NGF SIGNALLING VIA TRKA FROM THE PLASMA MEMBRANE 4.01e-04 5.31e-02 NGF SIGNALLING VIA TRKA FROM THE PLASMA MEMBRANE 7.53e-04 9.17e-02 SEROTONIN RECEPTORS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.76e-05 6.95e-02 abnormal food intake 1.96e-05 7.47e-02 increased circulating insulin level 3.75e-05 1.18e-01 decreased seminal vesicle weight 4.01e-05 1.24e-01 increased systemic arterial blood pressure 6.29e-05 1.66e-01 abnormal circulating calcium level 1.20e-04 2.54e-01 abnormal testes secretion 1.24e-04 2.59e-01 decreased circulating progesterone level 2.48e-04 3.97e-01 abnormal circadian phase 2.58e-04 4.08e-01 increased adrenal gland weight 3.43e-04 4.86e-01 shortened circadian period 3.98e-04 5.30e-01 obese 6.66e-04 7.18e-01 decreased lean body mass 6.82e-04 7.26e-01 abnormal bone mineralization 7.26e-04 7.53e-01 increased right ventricle systolic pressure 7.46e-04 7.62e-01 abnormal ovarian secretion 8.11e-04 7.97e-01 impaired glucose tolerance 9.16e-04 8.56e-01 abnormal glucose homeostasis 9.80e-04 8.93e-01 enlarged parathyroid gland 1.03e-03 9.16e-01 increased total body fat amount 1.05e-03 9.25e-01 abnormal vascular permeability

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

²FDR corrected p-value (Benjamini-Hochberg)