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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod213

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod213 Module size 65 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 53616 ADAM22 ADAM metallopeptidase domain 22 84335 AKT1S1 AKT1 substrate 1 23141 ANKLE2 ankyrin repeat and LEM domain containing 2 84446 BRSK1 BR serine/threonine kinase 1 84280 BTBD10 BTB domain containing 10 84254 CAMKK1 calcium/calmodulin dependent protein kinase kinase 1 10645 CAMKK2 calcium/calmodulin dependent protein kinase kinase 2 25776 CBY1 chibby family member 1, beta catenin antagonist 55704 CCDC88A coiled-coil domain containing 88A 994 CDC25B cell division cycle 25B 995 CDC25C cell division cycle 25C 387119 CEP85L centrosomal protein 85 like 84952 CGNL1 cingulin like 1 200186 CRTC2 CREB regulated transcription coactivator 2 54541 DDIT4 DNA damage inducible transcript 4 23136 EPB41L3 erythrocyte membrane protein band 4.1 like 3 51307 FAM53C family with sequence similarity 53 member C 137392 FAM92A1 family with sequence similarity 92 member A 2838 GPR15 G protein-coupled receptor 15 2932 GSK3B glycogen synthase kinase 3 beta 60598 KCNK15 potassium two pore domain channel subfamily K member 15 3777 KCNK3 potassium two pore domain channel subfamily K member 3 51305 KCNK9 potassium two pore domain channel subfamily K member 9 9778 KIAA0232 KIAA0232 303914 LSR immunoglobulin-like domain containing receptor 1 4137 MAPT microtubule associated protein tau 4139 MARK1 microtubule affinity regulating kinase 1 2011 MARK2 microtubule affinity regulating kinase 2 4140 MARK3 microtubule affinity regulating kinase 3 57787 MARK4 microtubule affinity regulating kinase 4 84206 MEX3B mex-3 RNA binding family member B 5562 PRKAA1 protein kinase AMP-activated catalytic subunit alpha 1 5563 PRKAA2 protein kinase AMP-activated catalytic subunit alpha 2 5564 PRKAB1 protein kinase AMP-activated non-catalytic subunit beta 1 5571 PRKAG1 protein kinase AMP-activated non-catalytic subunit gamma 1 53632 PRKAG3 protein kinase AMP-activated non-catalytic subunit gamma 3 55103 RALGPS2 Ral GEF with PH domain and SH3 binding motif 2 26166 RGS22 regulator of G protein signaling 22 64092 SAMSN1 SAM domain, SH3 domain and nuclear localization signals 1 25996 SFN RNA exonuclease 2 150094 SIK1 salt inducible kinase 1 23235 SIK2 salt inducible kinase 2 23387 SIK3 SIK family kinase 3 51629 SLC25A39 solute carrier family 25 member 39 6543 SLC8A2 solute carrier family 8 member A2 114798 SLITRK1 SLIT and NTRK like family member 1 387778 SPDYC speedy/RINGO cell cycle regulator family member C 6744 SSFA2 ITPR interacting domain containing 2 92335 STRADA STE20-related kinase adaptor alpha 55437 STRADB STE20-related kinase adaptor beta 7164 TPD52L1 TPD52 like 1 7248 TSC1 TSC complex subunit 1 7249 TSC2 TSC complex subunit 2 7351 UCP2 uncoupling protein 2 7352 UCP3 uncoupling protein 3 7529 YWHAB tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta 7531 YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon 7532 YWHAG tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma 7533 YWHAH tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta 10971 YWHAQ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta 7534 YWHAZ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta 55552 ZFP36 zinc finger protein 823 677 ZFP36L1 ZFP36 ring finger protein like 1 22882 ZHX2 zinc fingers and homeoboxes 2 55778 ZNF839 zinc finger protein 839

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 5.89e-01 1.16e-05 Reactome TWIK-releated acid-sensitive K+ channel (TASK) Neuronal System 3.62e-01 1.50e-17 Reactome Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex Cell Cycle 3.35e-01 7.47e-17 GO tau-protein kinase activity molecular_function 1.94e-01 3.47e-05 Reactome Inhibition of TSC complex formation by PKB Signal Transduction 1.81e-01 8.40e-12 GO AMP-activated protein kinase activity molecular_function 1.50e-01 1.32e-14 GO nucleotide-activated protein kinase complex cellular_component 9.92e-02 2.46e-14 Reactome Activation of BAD and translocation to mitochondria Programmed Cell Death 6.68e-02 8.78e-14 GO negative regulation of TOR signaling biological_process 6.04e-02 1.15e-04 Reactome The fatty acid cycling model Metabolism 5.49e-02 1.15e-04 Reactome Mitochondrial Uncoupling Proteins Metabolism 4.71e-02 3.34e-16 Reactome Energy dependent regulation of mTOR by LKB1-AMPK Signal Transduction 4.64e-02 1.15e-04 Reactome The proton buffering model Metabolism 4.01e-02 6.27e-19 Reactome mTOR signalling Signal Transduction 3.57e-02 3.06e-08 GO 14-3-3 protein binding molecular_function 2.47e-02 1.29e-12 GO positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway biological_process 2.44e-02 5.13e-04 GO negative regulation of erythrocyte differentiation biological_process 1.44e-02 4.64e-18 Reactome Translocation of SLC2A4 (GLUT4) to the plasma membrane Vesicle-mediated transport 8.39e-03 3.06e-08 GO regulation of microtubule cytoskeleton organization biological_process 2.98e-03 7.26e-23 Reactome TP53 Regulates Metabolic Genes Gene expression (Transcription) 1.40e-03 1.58e-09 GO establishment of cell polarity 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 2.63e-11 1.69e-08 AMP-activated protein kinase activity 4.58e-11 2.87e-08 protein serine/threonine kinase activity 1.85e-10 1.50e-07 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway 2.54e-10 1.48e-07 tau-protein kinase activity 4.28e-10 2.42e-07 protein kinase activity 6.75e-10 5.12e-07 mitochondrial transport 8.61e-10 6.46e-07 regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway 1.06e-09 7.88e-07 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway 1.66e-09 7.28e-07 nucleotide-activated protein kinase complex 3.46e-09 2.40e-06 negative regulation of TOR signaling 7.27e-09 3.38e-06 phosphotransferase activity, alcohol group as acceptor 1.80e-08 1.13e-05 regulation of mitochondrial membrane permeability 3.36e-08 1.40e-05 kinase binding 3.40e-08 2.06e-05 regulation of membrane permeability 8.07e-08 4.63e-05 regulation of mitochondrion organization 1.04e-07 5.86e-05 mitochondrial membrane organization 1.25e-07 6.95e-05 cell cycle arrest 1.47e-07 5.51e-05 14-3-3 protein binding 3.96e-07 2.02e-04 regulation of TOR signaling 4.04e-07 1.38e-04 protein kinase binding

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 ENERGY DEPENDENT REGULATION OF MTOR BY LKB1 AMPK 0.00e+00 0.00e+00 PKB MEDIATED EVENTS 0.00e+00 0.00e+00 ENERGY DEPENDENT REGULATION OF MTOR BY LKB1 AMPK 1.38e-12 4.08e-10 REGULATION OF RHEB GTPASE ACTIVITY BY AMPK 1.57e-12 6.15e-10 REGULATION OF RHEB GTPASE ACTIVITY BY AMPK 3.41e-12 1.33e-09 PKB MEDIATED EVENTS 1.73e-11 6.60e-09 ACTIVATED AMPK STIMULATES FATTY ACID OXIDATION IN MUSCLE 1.94e-11 7.38e-09 REGULATION OF AMPK ACTIVITY VIA LKB1 3.71e-10 9.53e-08 REGULATION OF AMPK ACTIVITY VIA LKB1 4.73e-10 1.20e-07 INSULIN RECEPTOR SIGNALLING CASCADE 6.15e-10 1.54e-07 ACTIVATED AMPK STIMULATES FATTY ACID OXIDATION IN MUSCLE 2.52e-09 5.87e-07 PI3K CASCADE 2.84e-09 6.58e-07 SIGNALING BY INSULIN RECEPTOR 2.40e-07 5.91e-05 INSULIN RECEPTOR SIGNALLING CASCADE 3.34e-07 8.04e-05 PI3K CASCADE 3.64e-07 8.73e-05 SIGNALING BY INSULIN RECEPTOR 9.03e-04 9.19e-02 TANDEM PORE DOMAIN POTASSIUM CHANNELS 1.35e-03 1.31e-01 REGULATION OF MRNA STABILITY BY PROTEINS THAT BIND AU RICH ELEMENTS 1.54e-03 1.48e-01 MITOTIC G2 G2 M PHASES 1.58e-03 1.51e-01 SIGNALING BY HIPPO

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.94e-06 1.43e-02 abnormal glucose homeostasis 2.98e-06 2.00e-02 decreased circulating insulin level 4.97e-06 2.93e-02 decreased susceptibility to diet-induced obesity 4.43e-05 1.31e-01 decreased susceptibility to hepatic steatosis 4.83e-05 1.39e-01 decreased circulating leptin level 5.25e-05 1.48e-01 improved glucose tolerance 2.10e-04 3.59e-01 decreased brown adipose tissue amount 2.21e-04 3.70e-01 hypermyelination 2.50e-04 3.99e-01 decreased circulating glucose level 2.53e-04 4.02e-01 increased insulin sensitivity 3.57e-04 4.96e-01 abnormal contextual conditioning behavior 4.37e-04 5.60e-01 increased hepatic hemangioma incidence 5.05e-04 6.08e-01 increased myocardial infarction size 6.71e-04 7.20e-01 increased adiponectin level 8.47e-04 8.20e-01 decreased coping response 9.03e-04 8.49e-01 abnormal adipocyte glucose uptake 9.44e-04 8.73e-01 increased renal carcinoma incidence 1.67e-03 1.00e+00 decreased glycogen level 1.78e-03 1.00e+00 increased red blood cell distribution width 3.12e-03 1.00e+00 abnormal circulating hormone level

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

²FDR corrected p-value (Benjamini-Hochberg)