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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod79

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod79 Module size 71 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 8165 AKAP1 A-kinase anchoring protein 1 10270 AKAP8 A-kinase anchoring protein 8 2668 ATF1 glial cell derived neurotrophic factor 2668 ATF2 glial cell derived neurotrophic factor 468 ATF4 activating transcription factor 4 22809 ATF5 activating transcription factor 5 84281 C2orf88 chromosome 2 open reading frame 88 1385 CREB1 cAMP responsive element binding protein 1 148327 CREB3 cAMP responsive element binding protein 3 like 4 90993 CREB3L1 cAMP responsive element binding protein 3 like 1 64764 CREB3L2 cAMP responsive element binding protein 3 like 2 84699 CREB3L3 cAMP responsive element binding protein 3 like 3 148327 CREB3L4 cAMP responsive element binding protein 3 like 4 153222 CREBRF CREB3 regulatory factor 1390 CREM cAMP responsive element modulator 1397 CRIP2 cysteine rich protein 2 23373 CRTC1 CREB regulated transcription coactivator 1 64784 CRTC3 CREB regulated transcription coactivator 3 9750 FAM65B RHO family interacting cell polarization regulator 2 2353 FOS Fos proto-oncogene, AP-1 transcription factor subunit 10537 GABBR1 ubiquitin D 23432 GPR161 G protein-coupled receptor 161 2845 GPR22 G protein-coupled receptor 22 117245 HRASLS5 HRAS like suppressor family member 5 3753 KCNE1 potassium voltage-gated channel subfamily E regulatory subunit 1 3767 KCNJ11 potassium voltage-gated channel subfamily J member 11 3778 KCNMA1 potassium calcium-activated channel subfamily M alpha 1 27094 KCNMB3 potassium calcium-activated channel subfamily M regulatory beta subunit 3 85442 KNDC1 kinase non-catalytic C-lobe domain containing 1 3991 LIPE lipase E, hormone sensitive type 10894 LYVE1 lymphatic vessel endothelial hyaluronan receptor 1 23173 MAP1A methionyl aminopeptidase 1 22877 MLXIP MLX interacting protein 4772 NFATC1 nuclear factor of activated T cells 1 4773 NFATC2 nuclear factor of activated T cells 2 4775 NFATC3 nuclear factor of activated T cells 3 79570 NKAIN1 sodium/potassium transporting ATPase interacting 1 NA NPIPP1 4901 NRL neural retina leucine zipper 54827 NXPE4 neurexophilin and PC-esterase domain family member 4 445815 PALM2-AKAP2 PALM2-AKAP2 readthrough 25953 PDC PNKD, MBL domain containing 5140 PDE3B phosphodiesterase 3B 5174 PDZK1 PDZ domain containing 1 5257 PHKB phosphorylase kinase regulatory subunit beta 5260 PHKG1 phosphorylase kinase catalytic subunit gamma 1 5569 PKIA cAMP-dependent protein kinase inhibitor alpha 81488 POLR2M RNA polymerase II subunit M 5506 PPP1R3A protein phosphatase 1 regulatory subunit 3A 5507 PPP1R3C protein phosphatase 1 regulatory subunit 3C 5509 PPP1R3D protein phosphatase 1 regulatory subunit 3D 90673 PPP1R3E protein phosphatase 1 regulatory subunit 3E 5578 PRKACA protein kinase C alpha 5567 PRKACB protein kinase cAMP-activated catalytic subunit beta 5568 PRKACG protein kinase cAMP-activated catalytic subunit gamma 5613 PRKX protein kinase X-linked 5961 PRPH2 peripherin 2 10411 RAPGEF3 Rap guanine nucleotide exchange factor 3 11069 RAPGEF4 Rap guanine nucleotide exchange factor 4 56256 SERTAD4 SERTA domain containing 4 6494 SIPA1 signal-induced proliferation-associated 1 26037 SIPA1L1 signal induced proliferation associated 1 like 1 84912 SLC35B4 solute carrier family 35 member B4 6548 SLC9A1 solute carrier family 9 member A1 114815 SORCS1 sortilin related VPS10 domain containing receptor 1 3925 STMN1 stathmin 1 80834 TAS1R2 taste 1 receptor member 2 374403 TBC1D10C TBC1 domain family member 10C 7142 TNP2 transition protein 2 56302 TRPV5 transient receptor potential cation channel subfamily V member 5 10100 TSPAN2 tetraspanin 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 3.53e-01 2.12e-13 Reactome CREB3 factors activate genes Metabolism of proteins 2.15e-01 1.88e-06 Reactome Calcineurin activates NFAT Immune System 2.06e-01 2.99e-14 GO cAMP response element binding molecular_function 1.95e-01 6.90e-09 GO cAMP-dependent protein kinase activity molecular_function 1.51e-01 1.98e-11 Reactome Rap1 signalling Immune System 1.41e-01 6.90e-09 Reactome CREB phosphorylation through the activation of Adenylate Cyclase Neuronal System 1.21e-01 7.67e-03 Reactome Defective ABCC8 can cause hypoglycemias and hyperglycemias Disease 8.04e-02 8.01e-09 GO protein kinase A regulatory subunit binding molecular_function 7.27e-02 6.59e-08 GO glycogen metabolic process biological_process 6.94e-02 7.67e-03 Reactome PDE3B signalling Signal Transduction 4.84e-02 7.67e-03 Reactome PKB-mediated events Signal Transduction 3.72e-02 5.39e-07 Reactome PKA-mediated phosphorylation of key metabolic factors Metabolism 3.49e-02 5.14e-04 Reactome Ca2+ activated K+ channels Neuronal System 3.17e-02 3.02e-04 Reactome CREB phosphorylation Signal Transduction#Immune System 2.05e-02 7.82e-04 GO leucine zipper domain binding molecular_function 1.54e-02 4.24e-05 Reactome cGMP effects Hemostasis 1.26e-02 9.36e-04 Reactome Hyaluronan uptake and degradation Metabolism 2.58e-03 5.05e-06 Reactome MAPK targets/ Nuclear events mediated by MAP kinases Immune System

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 1.13e-11 7.49e-09 cAMP response element binding 9.37e-08 3.62e-05 cAMP-dependent protein kinase activity 2.33e-07 8.37e-05 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding 2.54e-07 9.07e-05 cAMP response element binding protein binding 6.83e-07 3.36e-04 glycogen metabolic process 1.65e-06 5.04e-04 protein kinase A regulatory subunit binding 2.57e-06 1.13e-03 energy reserve metabolic process 4.02e-06 1.70e-03 polysaccharide metabolic process 4.35e-06 1.82e-03 transcription from RNA polymerase II promoter 7.89e-06 3.13e-03 negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning 8.56e-06 2.27e-03 protein kinase A binding 1.67e-05 6.12e-03 regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning 1.76e-05 6.42e-03 response to unfolded protein 2.75e-05 9.51e-03 endoplasmic reticulum unfolded protein response 3.13e-05 1.06e-02 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress 3.22e-05 7.61e-03 RNA polymerase II transcription factor activity, sequence-specific DNA binding 3.50e-05 1.18e-02 cellular response to unfolded protein 6.01e-05 1.33e-02 RNA polymerase II regulatory region sequence-specific DNA binding 6.22e-05 1.37e-02 RNA polymerase II regulatory region DNA binding 6.62e-05 2.05e-02 cellular response to topologically incorrect protein

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.37e-09 3.28e-07 RAP1 SIGNALLING 1.01e-08 2.96e-06 RAP1 SIGNALLING 7.55e-07 1.34e-04 HORMONE SENSITIVE LIPASE HSL MEDIATED TRIACYLGLYCEROL HYDROLYSIS 3.53e-06 7.25e-04 HORMONE SENSITIVE LIPASE HSL MEDIATED TRIACYLGLYCEROL HYDROLYSIS 5.00e-06 7.86e-04 GLUCOSE METABOLISM 2.22e-05 3.14e-03 PKA MEDIATED PHOSPHORYLATION OF CREB 4.27e-05 5.79e-03 REGULATION OF INSULIN SECRETION BY GLUCAGON LIKE PEPTIDE1 4.34e-05 7.37e-03 GLUCOSE METABOLISM 6.37e-05 8.40e-03 LIPID DIGESTION MOBILIZATION AND TRANSPORT 9.54e-05 1.22e-02 REGULATION OF INSULIN SECRETION 1.22e-04 1.52e-02 METABOLISM OF CARBOHYDRATES 1.29e-04 1.95e-02 LIPID DIGESTION MOBILIZATION AND TRANSPORT 1.48e-04 2.20e-02 PKA MEDIATED PHOSPHORYLATION OF CREB 2.01e-04 2.38e-02 CA DEPENDENT EVENTS 2.25e-04 2.64e-02 MAPK TARGETS NUCLEAR EVENTS MEDIATED BY MAP KINASES 2.39e-04 3.36e-02 REGULATION OF INSULIN SECRETION BY GLUCAGON LIKE PEPTIDE1 2.49e-04 2.89e-02 GLUCONEOGENESIS 2.62e-04 3.03e-02 DAG AND IP3 SIGNALING 3.38e-04 3.82e-02 INTEGRATION OF ENERGY METABOLISM 3.44e-04 4.63e-02 REGULATION OF INSULIN SECRETION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.51e-04 2.97e-01 abnormal muscle cell glucose uptake 3.65e-04 5.03e-01 increased retinal cone cell number 7.60e-04 7.67e-01 insulin resistance 7.74e-04 7.75e-01 absent retinal rod cells 9.08e-04 8.52e-01 increased triglyceride level 9.16e-04 8.56e-01 decreased retinal rod cell number 9.78e-04 8.93e-01 increased insulin secretion 1.02e-03 9.10e-01 abnormal action potential 1.46e-03 1.00e+00 decreased trabecular bone thickness 1.56e-03 1.00e+00 abnormal glucose homeostasis 2.57e-03 1.00e+00 decreased glycogen level 2.91e-03 1.00e+00 increased circulating insulin level 3.77e-03 1.00e+00 increased pancreatic beta cell mass 4.42e-03 1.00e+00 abnormal white adipose tissue physiology 5.25e-03 1.00e+00 chondrodystrophy 5.72e-03 1.00e+00 tonic-clonic seizures 5.91e-03 1.00e+00 abnormal cued conditioning behavior 6.31e-03 1.00e+00 absence seizures 6.38e-03 1.00e+00 abnormal vestibular ganglion morphology 7.31e-03 1.00e+00 abnormal long bone diaphysis morphology

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

²FDR corrected p-value (Benjamini-Hochberg)