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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod41

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod41 Module size 78 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 27 ABL2 ABL proto-oncogene 2, non-receptor tyrosine kinase 558 AXL AXL receptor tyrosine kinase 660 BMX BMX non-receptor tyrosine kinase 29372 BTK RAS p21 protein activator 3 29775 CARD10 caspase recruitment domain family member 10 79092 CARD14 caspase recruitment domain family member 14 9578 CDC42BPB CDC42 binding protein kinase beta 25778 DSTYK dual serine/threonine and tyrosine protein kinase 2081 ERN1 endoplasmic reticulum to nucleus signaling 1 10595 ERN2 endoplasmic reticulum to nucleus signaling 2 53834 FGFRL1 fibroblast growth factor receptor like 1 2322 FLT3 fms related tyrosine kinase 3 2444 FRK fyn related Src family tyrosine kinase 30811 HUNK hormonally up-regulated Neu-associated kinase 80895 ILKAP ILK associated serine/threonine phosphatase 3645 INSRR insulin receptor related receptor 3697 ITIH1 inter-alpha-trypsin inhibitor heavy chain 1 3698 ITIH2 inter-alpha-trypsin inhibitor heavy chain 2 3699 ITIH3 inter-alpha-trypsin inhibitor heavy chain 3 3700 ITIH4 inter-alpha-trypsin inhibitor heavy chain family member 4 80760 ITIH5 inter-alpha-trypsin inhibitor heavy chain family member 5 347365 ITIH6 inter-alpha-trypsin inhibitor heavy chain family member 6 338785 KRT79 keratin 79 3984 LIMK1 LIM domain kinase 1 3985 LIMK2 LIM domain kinase 2 136332 LRGUK leucine rich repeats and guanylate kinase domain containing 4294 MAP3K10 mitogen-activated protein kinase kinase kinase 10 4296 MAP3K11 mitogen-activated protein kinase kinase kinase 11 4293 MAP3K9 mitogen-activated protein kinase kinase kinase 9 4145 MATK megakaryocyte-associated tyrosine kinase 10461 MERTK MER proto-oncogene, tyrosine kinase 197259 MLKL mixed lineage kinase domain like pseudokinase 4354 MPP1 membrane palmitoylated protein 1 4355 MPP2 membrane palmitoylated protein 2 4356 MPP3 membrane palmitoylated protein 3 3609 MPP4 interleukin enhancer binding factor 3 64398 MPP5 membrane palmitoylated protein 5 299173 MPP6 M phase phosphoprotein 6, pseudogene 8208 MPP7 chromatin assembly factor 1 subunit B 123263 MTFMT mitochondrial methionyl-tRNA formyltransferase 4593 MUSK muscle associated receptor tyrosine kinase 27347 PASK serine/threonine kinase 39 55872 PBK PDZ binding kinase 64146 PDF peptide deformylase, mitochondrial 5157 PDGFRL platelet derived growth factor receptor like 54704 PDP1 pyruvate dehyrogenase phosphatase catalytic subunit 1 57546 PDP2 pyruvate dehyrogenase phosphatase catalytic subunit 2 151649 PP2D1 protein phosphatase 2C like domain containing 1 60490 PPCDC phosphopantothenoylcysteine decarboxylase 79717 PPCS phosphopantothenoylcysteine synthetase 5495 PPM1B protein phosphatase, Mg2+/Mn2+ dependent 1B 8493 PPM1D protein phosphatase, Mg2+/Mn2+ dependent 1D 132160 PPM1E protein phosphatase, Mg2+/Mn2+ dependent 1M 9647 PPM1F protein phosphatase, Mg2+/Mn2+ dependent 1F 5496 PPM1G protein phosphatase, Mg2+/Mn2+ dependent 1G 152926 PPM1K protein phosphatase, Mg2+/Mn2+ dependent 1K 151742 PPM1L protein phosphatase, Mg2+/Mn2+ dependent 1L 147699 PPM1N protein phosphatase, Mg2+/Mn2+ dependent 1N (putative) 160760 PPTC7 PTC7 protein phosphatase homolog 5753 PTK6 protein tyrosine kinase 6 5754 PTK7 protein tyrosine kinase 7 (inactive) 4919 ROR1 receptor tyrosine kinase like orphan receptor 1 6120 RPE ribulose-5-phosphate-3-epimerase 7871 SLMAP sarcolemma associated protein 6725 SRMS src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites 83931 STK40 serine/threonine kinase 40 55359 STYK1 serine/threonine/tyrosine kinase 1 7016 TESK1 testis associated actin remodelling kinase 1 10420 TESK2 testis associated actin remodelling kinase 2 7075 TIE1 tyrosine kinase with immunoglobulin like and EGF like domains 1 27010 TPK1 thiamin pyrophosphokinase 1 10221 TRIB1 tribbles pseudokinase 1 28951 TRIB2 tribbles pseudokinase 2 7294 TXK TXK tyrosine kinase 7301 TYRO3 TYRO3 protein tyrosine kinase 4013 VWA5A von Willebrand factor A domain containing 5A 127731 VWA5B1 von Willebrand factor A domain containing 5B1 90113 VWA5B2 von Willebrand factor A domain containing 5B2

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 3.62e-01 1.83e-12 GO hyaluronan metabolic process biological_process 2.77e-01 1.85e-08 GO JUN kinase kinase kinase activity molecular_function 2.74e-01 5.04e-05 Reactome PTK6 Down-Regulation Signal Transduction 1.68e-01 3.12e-11 GO peptidyl-threonine dephosphorylation biological_process 8.44e-02 1.32e-13 GO non-membrane spanning protein tyrosine kinase activity molecular_function 8.27e-02 2.12e-17 GO protein serine/threonine phosphatase activity molecular_function 7.69e-02 7.96e-06 GO vagina development biological_process 7.69e-02 7.96e-06 GO secretion by cell biological_process 6.67e-02 1.45e-05 GO mitogen-activated protein kinase kinase binding molecular_function 5.94e-02 4.64e-04 Reactome Coenzyme A biosynthesis Metabolism 5.33e-02 5.92e-11 GO transmembrane receptor protein tyrosine kinase activity molecular_function 3.62e-02 5.95e-04 GO guanylate kinase activity molecular_function 2.38e-02 5.97e-11 GO peptidyl-tyrosine autophosphorylation biological_process 2.02e-02 4.64e-04 GO regulation of acetyl-CoA biosynthetic process from pyruvate biological_process 1.87e-02 4.11e-07 GO Wnt-protein binding molecular_function 1.63e-02 1.09e-05 GO natural killer cell differentiation biological_process 4.50e-03 4.42e-05 GO apoptotic cell clearance biological_process 2.66e-03 8.83e-06 GO mesoderm development 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 0.00e+00 0.00e+00 peptidyl-tyrosine phosphorylation 0.00e+00 0.00e+00 peptidyl-tyrosine autophosphorylation 0.00e+00 0.00e+00 protein dephosphorylation 0.00e+00 0.00e+00 protein kinase activity 0.00e+00 0.00e+00 phosphotransferase activity, alcohol group as acceptor 0.00e+00 0.00e+00 protein tyrosine kinase activity 0.00e+00 0.00e+00 protein serine/threonine phosphatase activity 0.00e+00 0.00e+00 phosphoprotein phosphatase activity 0.00e+00 0.00e+00 transmembrane receptor protein tyrosine kinase activity 2.52e-18 2.41e-15 protein autophosphorylation 3.85e-12 2.20e-09 extrinsic component of cytoplasmic side of plasma membrane 1.35e-11 8.87e-09 non-membrane spanning protein tyrosine kinase activity 3.16e-11 2.75e-08 peptidyl-threonine dephosphorylation 2.93e-10 1.42e-07 extrinsic component of plasma membrane 6.69e-10 5.09e-07 dephosphorylation 6.80e-10 3.12e-07 cytoplasmic side of plasma membrane 1.31e-09 5.80e-07 cytoplasmic side of membrane 3.81e-09 2.62e-06 hyaluronan metabolic process 4.06e-09 1.96e-06 phosphatase activity 4.12e-09 2.82e-06 transmembrane receptor protein tyrosine kinase signaling pathway

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 7.27e-04 8.89e-02 REGULATION OF PYRUVATE DEHYDROGENASE PDH COMPLEX 7.91e-04 8.14e-02 VITAMIN B5 PANTOTHENATE METABOLISM 1.17e-03 1.35e-01 PYRUVATE METABOLISM 1.21e-03 1.39e-01 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 1.56e-03 1.73e-01 SEMA4D IN SEMAPHORIN SIGNALING 1.84e-03 1.73e-01 SEMA4D INDUCED CELL MIGRATION AND GROWTH CONE COLLAPSE 2.09e-03 1.93e-01 REGULATION OF PYRUVATE DEHYDROGENASE PDH COMPLEX 2.36e-03 2.15e-01 METABOLISM OF VITAMINS AND COFACTORS 2.81e-03 2.50e-01 PYRUVATE METABOLISM 2.86e-03 2.89e-01 METABOLISM OF VITAMINS AND COFACTORS 2.88e-03 2.90e-01 VITAMIN B5 PANTOTHENATE METABOLISM 2.91e-03 2.58e-01 SEMA4D IN SEMAPHORIN SIGNALING 6.11e-03 5.39e-01 PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE 8.00e-03 6.72e-01 SEMAPHORIN INTERACTIONS 1.24e-02 8.77e-01 PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE 1.25e-02 8.83e-01 SEMAPHORIN INTERACTIONS 2.06e-02 1.00e+00 CELL JUNCTION ORGANIZATION 2.16e-02 1.00e+00 AXON GUIDANCE 2.51e-02 1.00e+00 SEMA3A PAK DEPENDENT AXON REPULSION 2.52e-02 1.00e+00 AXON GUIDANCE

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.70e-03 1e+00 abnormal small intestine morphology 2.01e-03 1e+00 abnormal bone marrow cell number 5.19e-03 1e+00 no spontaneous movement 5.37e-03 1e+00 thin diaphragm muscle 5.95e-03 1e+00 decreased interleukin-12 secretion 6.11e-03 1e+00 decreased splenocyte number 6.93e-03 1e+00 cyanosis 7.95e-03 1e+00 increased pro-B cell number 9.95e-03 1e+00 myeloid hyperplasia 1.25e-02 1e+00 abnormal respiratory quotient 1.31e-02 1e+00 dilated pulmonary artery 1.49e-02 1e+00 novel environmental response-related retropulsion 1.68e-02 1e+00 decreased IgD level 1.68e-02 1e+00 abnormal pro-B cell morphology 1.69e-02 1e+00 fusion of basioccipital and basisphenoid bone 1.69e-02 1e+00 pectus excavatum 1.86e-02 1e+00 abnormal pulp cavity morphology 1.86e-02 1e+00 decreased pancreatic beta cell proliferation 1.86e-02 1e+00 failure of neuromuscular synapse presynaptic differentiation 2.05e-02 1e+00 failure of neuromuscular synapse postsynaptic differentiation

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

²FDR corrected p-value (Benjamini-Hochberg)