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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod112

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod112 Module size 60 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 90 ACVR1 activin A receptor type 1 130399 ACVR1C activin A receptor type 1C 92 ACVR2A activin A receptor type 2A 197 AHSG alpha 2-HS glycoprotein 283 ANG angiogenin 51297 BPIFA1 BPI fold containing family A member 1 55997 CFC1 cripto, FRL-1, cryptic family 1 1113 CGA chromogranin A 93659 CGB chorionic gonadotropin subunit beta 5 93659 CGB5 chorionic gonadotropin subunit beta 5 94027 CGB7 chorionic gonadotropin subunit beta 7 8483 CILP cartilage intermediate layer protein 4435 CITED1 Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1 2022 ENG endoglin 644815 FAM83G family with sequence similarity 83 member G 3075 FHL1 complement factor H 2488 FSHB follicle stimulating hormone subunit beta 10272 FSTL3 follistatin like 3 9569 GTF2IRD1 GTF2I repeat domain containing 1 3547 IGSF1 immunoglobulin superfamily member 1 137797 LYPD2 LY6/PLAUR domain containing 2 284358 MAMSTR MEF2 activating motif and SAP domain containing transcriptional regulator 10763 NES nestin 147111 NOTUM notum, palmitoleoyl-protein carboxylesterase 100506658 OCLN occludin 23089 PEG10 paternally expressed 10 58473 PLEKHB1 pleckstrin homology domain containing B1 55111 PLEKHJ1 pleckstrin homology domain containing J1 51177 PLEKHO1 pleckstrin homology domain containing O1 56937 PMEPA1 prostate transmembrane protein, androgen induced 1 57479 PRR12 proline rich 12 5680 PSG11 pregnancy specific beta-1-glycoprotein 11 5678 PSG9 pregnancy specific beta-1-glycoprotein 9 28984 RGCC regulator of cell cycle 9028 RHBDL1 rhomboid like 1 54933 RHBDL2 rhomboid like 2 54778 RNF111 ring finger protein 111 6050 RNH1 ribonuclease/angiogenin inhibitor 1 860 RUNX2 runt related transcription factor 2 54440 SASH3 SAM and SH3 domain containing 3 373541 SKI TATA-box binding protein associated factor 9 6498 SKIL SKI like proto-oncogene 2617 SMAD1 glycyl-tRNA synthetase 4087 SMAD2 SMAD family member 2 4088 SMAD3 SMAD family member 3 4089 SMAD4 SMAD family member 4 4092 SMAD7 SMAD family member 7 114790 STK11IP serine/threonine kinase 11 interacting protein 343521 TCTEX1D4 Tctex1 domain containing 4 6998 TDGF1 teratocarcinoma-derived growth factor 1 pseudogene 3 7040 TGFB1 transforming growth factor beta 1 7046 TGFBR1 transforming growth factor beta receptor 1 7048 TGFBR2 transforming growth factor beta receptor 2 7049 TGFBR3 transforming growth factor beta receptor 3 3196 TLX2 T cell leukemia homeobox 2 944 TNFSF8 TNF superfamily member 8 55223 TRIM62 tripartite motif containing 62 8848 TSC22D1 TSC22 domain family member 1 79674 VEPH1 ventricular zone expressed PH domain containing 1 9372 ZFYVE9 zinc finger FYVE-type containing 9

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 2.95e-01 2.03e-18 Reactome SMAD2/3 MH2 Domain Mutants in Cancer Disease 2.92e-01 2.03e-18 Reactome Loss of Function of SMAD2/3 in Cancer Disease 2.59e-01 7.33e-20 GO activin binding molecular_function 1.84e-01 6.05e-09 GO negative regulation of activin receptor signaling pathway biological_process 1.50e-01 9.64e-05 Reactome Glycoprotein hormones Metabolism of proteins 1.49e-01 3.17e-11 GO nodal signaling pathway biological_process 4.68e-02 3.03e-09 GO type II transforming growth factor beta receptor binding molecular_function 4.08e-02 3.47e-06 GO positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus biological_process 2.15e-02 2.06e-17 GO BMP signaling pathway biological_process 1.99e-02 2.53e-26 GO transforming growth factor beta receptor signaling pathway biological_process 1.88e-02 7.02e-11 Reactome Downregulation of SMAD2/3:SMAD4 transcriptional activity Signal Transduction#Gene expression (Transcription) 1.87e-02 4.24e-08 GO co-SMAD binding molecular_function 1.81e-02 3.31e-13 GO type I transforming growth factor beta receptor binding molecular_function 1.40e-02 4.76e-06 GO response to transforming growth factor beta biological_process 1.26e-02 1.22e-12 GO pathway-restricted SMAD protein phosphorylation biological_process 8.82e-03 9.40e-03 Reactome RUNX2 regulates genes involved in differentiation of myeloid cells Gene expression (Transcription) 7.78e-03 9.45e-17 GO negative regulation of transforming growth factor beta receptor signaling pathway biological_process 3.51e-03 1.24e-06 GO positive regulation of transforming growth factor beta receptor signaling pathway 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 transforming growth factor beta receptor signaling pathway 0.00e+00 0.00e+00 cellular response to transforming growth factor beta stimulus 0.00e+00 0.00e+00 response to transforming growth factor beta 0.00e+00 0.00e+00 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway 0.00e+00 0.00e+00 regulation of cellular response to growth factor stimulus 0.00e+00 0.00e+00 regulation of transforming growth factor beta receptor signaling pathway 0.00e+00 0.00e+00 SMAD binding 0.00e+00 0.00e+00 signal transducer activity, downstream of receptor 1.88e-19 1.80e-16 transmembrane receptor protein serine/threonine kinase signaling pathway 5.98e-12 5.43e-09 negative regulation of transforming growth factor beta receptor signaling pathway 2.14e-11 1.89e-08 negative regulation of cellular response to transforming growth factor beta stimulus 6.62e-11 4.10e-08 transforming growth factor beta receptor binding 1.30e-10 1.07e-07 SMAD protein complex assembly 2.28e-10 1.82e-07 enzyme linked receptor protein signaling pathway 3.61e-10 2.83e-07 regulation of epithelial to mesenchymal transition 5.79e-10 3.18e-07 transforming growth factor beta receptor, cytoplasmic mediator activity 7.22e-10 3.91e-07 activin binding 7.78e-10 4.20e-07 transmembrane receptor protein serine/threonine kinase activity 9.37e-10 7.01e-07 BMP signaling pathway 1.07e-09 7.95e-07 positive regulation of epithelial to mesenchymal transition

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 TGF BETA RECEPTOR SIGNALING ACTIVATES SMADS 0.00e+00 0.00e+00 SIGNALING BY TGF BETA RECEPTOR COMPLEX 0.00e+00 0.00e+00 DOWNREGULATION OF TGF BETA RECEPTOR SIGNALING 0.00e+00 0.00e+00 TGF BETA RECEPTOR SIGNALING ACTIVATES SMADS 0.00e+00 0.00e+00 SIGNALING BY TGF BETA RECEPTOR COMPLEX 0.00e+00 0.00e+00 DOWNREGULATION OF TGF BETA RECEPTOR SIGNALING 1.12e-10 3.04e-08 SIGNALING BY NODAL 4.55e-10 1.55e-07 SIGNALING BY NODAL 1.07e-08 2.34e-06 TRANSCRIPTIONAL ACTIVITY OF SMAD2 SMAD3 SMAD4 HETEROTRIMER 1.61e-08 3.45e-06 DOWNREGULATION OF SMAD2 3 SMAD4 TRANSCRIPTIONAL ACTIVITY 3.96e-08 1.07e-05 SIGNALING BY BMP 5.63e-08 1.50e-05 TRANSCRIPTIONAL ACTIVITY OF SMAD2 SMAD3 SMAD4 HETEROTRIMER 7.18e-08 1.42e-05 SIGNALING BY BMP 1.46e-07 3.71e-05 DOWNREGULATION OF SMAD2 3 SMAD4 TRANSCRIPTIONAL ACTIVITY 2.04e-07 3.85e-05 GLYCOPROTEIN HORMONES 2.47e-07 6.08e-05 GLYCOPROTEIN HORMONES 3.93e-07 7.22e-05 PEPTIDE HORMONE BIOSYNTHESIS 6.12e-07 1.42e-04 PEPTIDE HORMONE BIOSYNTHESIS 5.41e-06 8.45e-04 SMAD2 SMAD3 SMAD4 HETEROTRIMER REGULATES TRANSCRIPTION 1.62e-05 2.98e-03 SMAD2 SMAD3 SMAD4 HETEROTRIMER REGULATES TRANSCRIPTION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 8.52e-06 4.18e-02 abnormal extraembryonic tissue morphology 1.69e-05 6.79e-02 abnormal visceral endoderm morphology 1.80e-05 7.03e-02 rostral body truncation 8.31e-05 2.01e-01 abnormal embryonic epiblast morphology 1.73e-04 3.21e-01 absent vitelline blood vessels 2.23e-04 3.73e-01 increased susceptibility to kidney reperfusion injury 4.06e-04 5.36e-01 dilated aorta bulb 4.82e-04 5.95e-01 absent mesoderm 6.12e-04 6.82e-01 abnormal mesoderm development 7.25e-04 7.53e-01 abnormal chorion morphology 9.04e-04 8.50e-01 failure of chorioallantoic fusion 9.79e-04 8.93e-01 ascending aorta aneurysm 9.79e-04 8.93e-01 abnormal aorta bulb morphology 1.05e-03 9.25e-01 abnormal primitive streak formation 1.06e-03 9.29e-01 abnormal femur morphology 1.12e-03 9.61e-01 absent frontal bone 1.17e-03 9.85e-01 stomach inflammation 1.21e-03 1.00e+00 failure of primitive streak formation 1.80e-03 1.00e+00 abnormal heart development 1.82e-03 1.00e+00 abnormal embryonic hematopoiesis

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

²FDR corrected p-value (Benjamini-Hochberg)