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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod191

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod191 Module size 31 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 189 AGT alanine--glyoxylate and serine--pyruvate aminotransferase 265 AMELX amelogenin X-linked 266 AMELY amelogenin Y-linked 351 APP amyloid beta precursor protein 553 AVPR1B arginine vasopressin receptor 1B 4345 CD200 CD200 molecule 131450 CD200R1 CD200 receptor 1 344807 CD200R1L CD200 receptor 1 like 1363 CPE carboxypeptidase E 2520 GAST gastrin 2767 GNA11 G protein subunit alpha 11 9630 GNA14 G protein subunit alpha 14 2776 GNAQ G protein subunit alpha q 54331 GNG2 G protein subunit gamma 2 2869 GRK5 G protein-coupled receptor kinase 5 3827 KNG1 kininogen 1 4142 MAS1 MAS1 proto-oncogene, G protein-coupled receptor 4224 MEP1A meprin A subunit alpha 4225 MEP1B meprin A subunit beta 10893 MMP24 matrix metallopeptidase 24 64231 MS4A6A membrane spanning 4-domains A6A 221391 OPN5 opsin 5 23236 PLCB1 phospholipase C beta 1 5330 PLCB2 phospholipase C beta 2 5331 PLCB3 phospholipase C beta 3 5332 PLCB4 phospholipase C beta 4 5550 PREP prolyl endopeptidase 60626 RIC8A RIC8 guanine nucleotide exchange factor A 55188 RIC8B RIC8 guanine nucleotide exchange factor B 26165 SPATA31A7 SPATA31 subfamily A member 7 169981 SPIN3 spindlin family member 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 2.13e-01 1.81e-16 Reactome Free fatty acids regulate insulin secretion Metabolism 2.12e-01 1.81e-16 Reactome Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion Metabolism 1.03e-01 1.35e-15 Reactome Acetylcholine regulates insulin secretion Metabolism 5.31e-02 1.35e-09 GO phospholipase C activity molecular_function 2.14e-02 4.53e-03 Reactome Defective AVP causes neurohypophyseal diabetes insipidus (NDI) Disease 7.60e-03 6.94e-21 Reactome G alpha (q) signalling events 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 4.98e-08 2.95e-05 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger 4.65e-07 2.35e-04 adenylate cyclase-modulating G-protein coupled receptor signaling pathway 2.41e-06 1.06e-03 dopamine receptor signaling pathway 2.47e-06 1.09e-03 activation of phospholipase C activity 2.86e-06 1.24e-03 Wnt signaling pathway, calcium modulating pathway 5.64e-06 2.31e-03 inositol phosphate metabolic process 5.66e-06 1.45e-03 heterotrimeric G-protein complex 5.70e-06 2.33e-03 phospholipase C-activating dopamine receptor signaling pathway 6.99e-06 1.88e-03 phosphatidylinositol phospholipase C activity 7.13e-06 2.85e-03 G-protein coupled acetylcholine receptor signaling pathway 8.32e-06 2.21e-03 phospholipase C activity 1.09e-05 4.19e-03 positive regulation of phospholipase C activity 1.36e-05 5.09e-03 regulation of phospholipase C activity 1.63e-05 4.08e-03 structural constituent of tooth enamel 1.84e-05 6.68e-03 response to acetylcholine 1.84e-05 6.68e-03 acetylcholine receptor signaling pathway 1.93e-05 4.77e-03 G-protein beta/gamma-subunit complex binding 1.98e-05 4.88e-03 type 2A serotonin receptor binding 3.62e-05 1.21e-02 positive regulation of phospholipase activity 5.60e-05 1.77e-02 positive regulation of lipase activity

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 GASTRIN CREB SIGNALLING PATHWAY VIA PKC AND MAPK 0.00e+00 0.00e+00 G ALPHA Q SIGNALLING EVENTS 0.00e+00 0.00e+00 GASTRIN CREB SIGNALLING PATHWAY VIA PKC AND MAPK 0.00e+00 0.00e+00 G ALPHA Q SIGNALLING EVENTS 6.08e-12 1.79e-09 REGULATION OF INSULIN SECRETION BY ACETYLCHOLINE 2.03e-10 7.19e-08 REGULATION OF INSULIN SECRETION BY ACETYLCHOLINE 8.54e-07 1.50e-04 REGULATION OF INSULIN SECRETION 3.63e-06 7.43e-04 REGULATION OF INSULIN SECRETION 4.07e-06 6.45e-04 INTEGRATION OF ENERGY METABOLISM 1.79e-05 3.26e-03 INTEGRATION OF ENERGY METABOLISM 1.88e-05 3.41e-03 CLASS A1 RHODOPSIN LIKE RECEPTORS 2.01e-05 2.87e-03 G BETA GAMMA SIGNALLING THROUGH PLC BETA 2.63e-05 3.68e-03 THROMBOXANE SIGNALLING THROUGH TP RECEPTOR 3.99e-05 6.84e-03 GPCR LIGAND BINDING 4.34e-05 5.88e-03 ADP SIGNALLING THROUGH P2RY1 4.65e-05 7.81e-03 PEPTIDE LIGAND BINDING RECEPTORS 6.03e-05 7.98e-03 ACTIVATION OF KAINATE RECEPTORS UPON GLUTAMATE BINDING 6.42e-05 8.46e-03 THROMBIN SIGNALLING THROUGH PROTEINASE ACTIVATED RECEPTORS PARS 6.56e-05 8.63e-03 G PROTEIN BETA GAMMA SIGNALLING 8.46e-05 1.10e-02 SIGNAL AMPLIFICATION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.59e-04 4.09e-01 increased ear pigmentation 3.63e-04 5.02e-01 abnormal renal/urinary system physiology 5.41e-04 6.37e-01 decreased circulating adrenocorticotropin level 6.17e-04 6.83e-01 increased kidney weight 7.70e-04 7.73e-01 increased tail pigmentation 7.81e-04 7.79e-01 proximal convoluted tubule brush border loss 1.01e-03 9.05e-01 increased foot pad pigmentation 1.93e-03 1.00e+00 hyperpigmentation 2.31e-03 1.00e+00 abnormal adipose tissue amount 2.66e-03 1.00e+00 darkened coat color 5.58e-03 1.00e+00 decreased urine sodium level 5.77e-03 1.00e+00 abnormal blood homeostasis 6.08e-03 1.00e+00 renal interstitial fibrosis 6.68e-03 1.00e+00 decreased circulating sodium level 7.03e-03 1.00e+00 increased anxiety-related response 7.52e-03 1.00e+00 decreased urine aldosterone level 7.66e-03 1.00e+00 abnormal leukocyte physiology 9.11e-03 1.00e+00 decreased thermal nociceptive threshold 9.38e-03 1.00e+00 increased circulating antidiuretic hormone level 1.12e-02 1.00e+00 increased urine flow rate

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

²FDR corrected p-value (Benjamini-Hochberg)