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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod261

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod261 Module size 44 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 207 AKT1 AKT serine/threonine kinase 1 208 AKT2 AKT serine/threonine kinase 2 10000 AKT3 AKT serine/threonine kinase 3 113763 C7orf29 ZBED6 C-terminal like 51063 CALHM2 calcium homeostasis modulator family member 2 2931 GSK3A glycogen synthase kinase 3 alpha 221895 JAZF1 JAZF zinc finger 1 120892 LRRK2 leucine rich repeat kinase 2 389840 MAP3K15 mitogen-activated protein kinase kinase kinase 15 80122 MAP3K19 mitogen-activated protein kinase kinase kinase 19 10746 MAP3K2 mitogen-activated protein kinase kinase kinase 2 4215 MAP3K3 mitogen-activated protein kinase kinase kinase 3 4217 MAP3K5 mitogen-activated protein kinase kinase kinase 5 9064 MAP3K6 mitogen-activated protein kinase kinase kinase 6 5596 MAPK4 mitogen-activated protein kinase 4 5597 MAPK6 mitogen-activated protein kinase 6 5598 MAPK7 mitogen-activated protein kinase 7 23332 MAST1 cytoplasmic linker associated protein 1 23139 MAST2 microtubule associated serine/threonine kinase 2 23031 MAST3 microtubule associated serine/threonine kinase 3 375449 MAST4 microtubule associated serine/threonine kinase family member 4 5585 PKN1 protein kinase N1 5586 PKN2 protein kinase N2 29941 PKN3 protein kinase N3 94274 PPP1R14A protein phosphatase 1 regulatory inhibitor subunit 14A 5578 PRKCA protein kinase C alpha 5579 PRKCB protein kinase C beta 5580 PRKCD protein kinase C delta 5581 PRKCE protein kinase C epsilon 5582 PRKCG protein kinase C gamma 5583 PRKCH protein kinase C eta 5588 PRKCQ protein kinase C theta 6195 RPS6KA1 ribosomal protein S6 kinase A1 6196 RPS6KA2 ribosomal protein S6 kinase A2 6197 RPS6KA3 ribosomal protein S6 kinase A3 8986 RPS6KA4 ribosomal protein S6 kinase A4 9252 RPS6KA5 ribosomal protein S6 kinase A5 27330 RPS6KA6 ribosomal protein S6 kinase A6 6198 RPS6KB1 ribosomal protein S6 kinase B1 6446 SGK1 serum/glucocorticoid regulated kinase 1 6703 SPRR2D small proline rich protein 2D 9623 TCL1B T cell leukemia/lymphoma 1B 79639 TMEM53 transmembrane protein 53 9671 WSCD2 WSC domain containing 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 4.30e-01 5.44e-24 GO protein kinase C activity molecular_function 3.80e-01 5.04e-08 Reactome AKT-mediated inactivation of FOXO1A Developmental Biology 2.73e-01 4.18e-10 Reactome RSK activation Neuronal System 2.00e-01 9.73e-10 Reactome CREB phosphorylation Signal Transduction#Immune System 1.39e-01 5.04e-10 GO MAP kinase kinase kinase activity molecular_function 1.11e-01 5.04e-08 GO calcium-dependent protein kinase C activity molecular_function 9.10e-02 4.77e-03 Reactome Signalling to ERK5 Signal Transduction 4.14e-02 1.80e-36 GO peptidyl-serine phosphorylation biological_process 4.14e-02 2.75e-08 Reactome AKT phosphorylates targets in the cytosol Signal Transduction 2.61e-02 4.57e-11 Reactome Recycling pathway of L1 Developmental Biology 2.48e-02 5.76e-11 GO protein serine/threonine/tyrosine kinase activity molecular_function 1.75e-02 4.51e-06 GO MAP kinase activity molecular_function 1.45e-02 2.06e-06 GO histone phosphorylation biological_process 1.20e-02 7.01e-07 Reactome RUNX2 regulates genes involved in cell migration Gene expression (Transcription) 9.50e-03 1.26e-07 Reactome Disinhibition of SNARE formation Hemostasis 5.05e-03 2.47e-04 GO negative regulation of cytokine production biological_process 4.80e-03 1.19e-09 Reactome ERK/MAPK targets Signal Transduction#Immune System 2.37e-03 2.51e-12 Reactome G alpha (z) 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 0.00e+00 0.00e+00 peptidyl-serine phosphorylation 0.00e+00 0.00e+00 protein kinase activity 0.00e+00 0.00e+00 protein serine/threonine kinase activity 0.00e+00 0.00e+00 phosphotransferase activity, alcohol group as acceptor 0.00e+00 0.00e+00 protein kinase C activity 1.32e-11 8.69e-09 magnesium ion binding 1.77e-10 1.05e-07 signal transducer, downstream of receptor, with serine/threonine kinase activity 1.91e-09 9.70e-07 protein serine/threonine/tyrosine kinase activity 9.80e-09 4.48e-06 signal transducer activity, downstream of receptor 1.37e-08 8.77e-06 histone phosphorylation 3.13e-08 1.31e-05 MAP kinase kinase kinase activity 1.13e-06 5.31e-04 activation of MAPKK activity 1.24e-06 3.86e-04 calcium-independent protein kinase C activity 1.71e-06 5.20e-04 calcium-dependent protein kinase C activity 2.61e-06 1.14e-03 platelet activation 2.63e-06 1.15e-03 negative regulation of insulin receptor signaling pathway 4.45e-06 1.24e-03 protein kinase binding 5.39e-06 2.21e-03 peptidyl-threonine phosphorylation 6.63e-06 2.67e-03 regulation of cellular response to insulin stimulus 1.35e-05 3.43e-03 kinase binding

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.52e-07 2.90e-05 NGF SIGNALLING VIA TRKA FROM THE PLASMA MEMBRANE 1.36e-06 3.01e-04 NGF SIGNALLING VIA TRKA FROM THE PLASMA MEMBRANE 2.20e-06 3.62e-04 RECYCLING PATHWAY OF L1 2.30e-06 3.78e-04 SIGNALLING BY NGF 3.52e-06 7.23e-04 RECYCLING PATHWAY OF L1 6.42e-06 9.89e-04 PLATELET ACTIVATION SIGNALING AND AGGREGATION 9.08e-06 1.36e-03 GASTRIN CREB SIGNALLING PATHWAY VIA PKC AND MAPK 1.32e-05 1.93e-03 SIGNAL TRANSDUCTION BY L1 1.56e-05 2.26e-03 EFFECTS OF PIP2 HYDROLYSIS 1.60e-05 2.32e-03 G ALPHA Z SIGNALLING EVENTS 1.76e-05 3.21e-03 SIGNALLING BY NGF 2.29e-05 4.09e-03 EFFECTS OF PIP2 HYDROLYSIS 3.05e-05 5.35e-03 G ALPHA Z SIGNALLING EVENTS 5.16e-05 8.59e-03 GASTRIN CREB SIGNALLING PATHWAY VIA PKC AND MAPK 5.21e-05 8.67e-03 SIGNAL TRANSDUCTION BY L1 6.79e-05 1.10e-02 ERK MAPK TARGETS 6.93e-05 9.08e-03 L1CAM INTERACTIONS 1.14e-04 1.43e-02 ERK MAPK TARGETS 1.24e-04 1.88e-02 NUCLEAR EVENTS KINASE AND TRANSCRIPTION FACTOR ACTIVATION 1.56e-04 1.89e-02 AKT PHOSPHORYLATES TARGETS IN THE CYTOSOL

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.06e-06 9.10e-03 decreased response of heart to induced stress 1.35e-04 2.78e-01 abnormal adipocyte glucose uptake 4.14e-04 5.42e-01 decreased DN1 thymic pro-T cell number 5.21e-04 6.20e-01 abnormal muscle cell glucose uptake 9.92e-04 8.99e-01 abnormal effector T cell morphology 1.12e-03 9.61e-01 decreased liver triglyceride level 1.86e-03 1.00e+00 increased insulin sensitivity 2.10e-03 1.00e+00 increased susceptibility to neuronal excitotoxicity 2.20e-03 1.00e+00 decreased physiological sensitivity to xenobiotic 2.59e-03 1.00e+00 increased skin papilloma incidence 2.84e-03 1.00e+00 abnormal contextual conditioning behavior 4.50e-03 1.00e+00 abnormal type II pneumocyte morphology 5.80e-03 1.00e+00 decreased circulating leptin level 6.78e-03 1.00e+00 impaired glucose tolerance 7.48e-03 1.00e+00 carpoptosis 7.52e-03 1.00e+00 thin hypodermis 8.50e-03 1.00e+00 abnormal dendritic spine morphology 9.34e-03 1.00e+00 abnormal renal sodium ion transport 9.35e-03 1.00e+00 decreased keratinocyte apoptosis 1.12e-02 1.00e+00 enlarged axillary lymph nodes

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

²FDR corrected p-value (Benjamini-Hochberg)