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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod159

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod159 Module size 46 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 91 ACVR1B activin A receptor type 1B 93 ACVR2B activin A receptor type 2B 94 ACVRL1 activin A receptor like type 1 268 AMH anti-Mullerian hormone 269 AMHR2 anti-Mullerian hormone receptor type 2 300016 BAMBI secreted Ly6/Plaur domain containing 1 27302 BMP10 bone morphogenetic protein 10 650 BMP2 bone morphogenetic protein 2 652 BMP4 bone morphogenetic protein 4 653 BMP5 bone morphogenetic protein 5 654 BMP6 bone morphogenetic protein 6 655 BMP7 bone morphogenetic protein 7 353500 BMP8A bone morphogenetic protein 8a 656 BMP8B bone morphogenetic protein 8b 168667 BMPER BMP binding endothelial regulator 657 BMPR1A bone morphogenetic protein receptor type 1A 658 BMPR1B bone morphogenetic protein receptor type 1B 659 BMPR2 bone morphogenetic protein receptor type 2 9350 CER1 cerberus 1, DAN family BMP antagonist 117275 CHRD chordin 91851 CHRDL1 chordin like 1 25884 CHRDL2 chordin like 2 10468 FST follistatin 11167 FSTL1 follistatin like 1 8200 GDF5 growth differentiation factor 5 392255 GDF6 growth differentiation factor 6 151449 GDF7 growth differentiation factor 7 26585 GREM1 gremlin 1, DAN family BMP antagonist 64388 GREM2 gremlin 2, DAN family BMP antagonist 3623 INHA inhibin subunit alpha 3624 INHBA inhibin subunit beta A 3625 INHBB inhibin subunit beta B 3626 INHBC inhibin subunit beta C 83729 INHBE inhibin subunit beta E 1482 NKX2-5 NK2 homeobox 5 4838 NODAL nodal growth differentiation factor 9241 NOG noggin 23645 PPP1R15A protein phosphatase 1 regulatory subunit 15A 56963 RGMA repulsive guidance molecule BMP co-receptor a 285704 RGMB repulsive guidance molecule BMP co-receptor b 4090 SMAD5 SMAD family member 5 4091 SMAD6 SMAD family member 6 4093 SMAD9 SMAD family member 9 25928 SOSTDC1 sclerostin domain containing 1 57045 TWSG1 twisted gastrulation BMP signaling modulator 1 9765 ZFYVE16 zinc finger FYVE-type containing 16

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 3.40e-01 7.18e-08 Reactome Antagonism of Activin by Follistatin Signal Transduction 2.97e-01 1.39e-41 Reactome Signaling by BMP Signal Transduction 2.75e-01 2.20e-17 GO BMP receptor binding molecular_function 1.85e-01 5.48e-14 GO BMP binding molecular_function 1.23e-01 2.32e-69 GO BMP signaling pathway biological_process 1.09e-01 1.61e-46 GO positive regulation of pathway-restricted SMAD protein phosphorylation biological_process 6.89e-02 1.57e-09 GO transforming growth factor beta receptor activity, type I molecular_function 5.37e-02 3.67e-37 GO transforming growth factor beta receptor binding molecular_function 3.70e-02 6.25e-07 GO morphogen activity molecular_function 2.42e-02 5.95e-33 GO cell development biological_process 1.93e-02 1.09e-42 Reactome Signaling by TGF-beta family members Signal Transduction 1.15e-02 2.83e-32 GO regulation of MAPK cascade biological_process 8.83e-03 1.47e-19 GO activin receptor signaling pathway biological_process 5.21e-03 5.82e-11 GO mesoderm formation 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 0e+00 0e+00 enzyme linked receptor protein signaling pathway 0e+00 0e+00 negative regulation of BMP signaling pathway 0e+00 0e+00 regulation of BMP signaling pathway 0e+00 0e+00 regulation of pathway-restricted SMAD protein phosphorylation 0e+00 0e+00 response to growth factor 0e+00 0e+00 cellular response to BMP stimulus 0e+00 0e+00 cellular response to growth factor stimulus 0e+00 0e+00 BMP signaling pathway 0e+00 0e+00 transmembrane receptor protein serine/threonine kinase signaling pathway 0e+00 0e+00 cartilage development 0e+00 0e+00 positive regulation of pathway-restricted SMAD protein phosphorylation 0e+00 0e+00 activin receptor signaling pathway 0e+00 0e+00 SMAD protein signal transduction 0e+00 0e+00 cytokine activity 0e+00 0e+00 cytokine receptor binding 0e+00 0e+00 transforming growth factor beta receptor binding 0e+00 0e+00 transmembrane receptor protein serine/threonine kinase activity 0e+00 0e+00 growth factor activity 0e+00 0e+00 BMP receptor binding 0e+00 0e+00 receptor serine/threonine 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 SIGNALING BY BMP 0.00e+00 0.00e+00 SIGNALING BY BMP 2.04e-10 5.39e-08 GLYCOPROTEIN HORMONES 2.39e-10 6.28e-08 PEPTIDE HORMONE BIOSYNTHESIS 3.25e-08 8.94e-06 GLYCOPROTEIN HORMONES 4.11e-08 1.11e-05 PEPTIDE HORMONE BIOSYNTHESIS 1.72e-05 3.16e-03 SIGNALING BY NODAL 2.75e-05 3.83e-03 SIGNALING BY NODAL 2.04e-03 1.89e-01 NETRIN1 SIGNALING 6.59e-03 5.21e-01 METABOLISM OF AMINO ACIDS AND DERIVATIVES 9.10e-03 7.43e-01 DEVELOPMENTAL BIOLOGY 1.12e-02 8.71e-01 METABOLISM OF AMINO ACIDS AND DERIVATIVES 1.23e-02 9.39e-01 NETRIN1 SIGNALING 2.49e-02 1.00e+00 DOWNREGULATION OF TGF BETA RECEPTOR SIGNALING 2.98e-02 1.00e+00 TGF BETA RECEPTOR SIGNALING ACTIVATES SMADS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 3.89e-07 4.28e-03 abnormal pectoral muscle morphology 5.38e-06 3.11e-02 failure of primitive streak formation 1.35e-05 5.72e-02 decreased rib number 2.87e-05 9.93e-02 abnormal foregut morphology 3.23e-05 1.07e-01 absent mesoderm 6.07e-05 1.62e-01 hydroureter 7.54e-05 1.87e-01 abnormal extraembryonic ectoderm morphology 9.21e-05 2.14e-01 increased ovary weight 1.83e-04 3.30e-01 abnormal cricoid cartilage morphology 2.30e-04 3.79e-01 abnormal thyroid cartilage morphology 4.37e-04 5.60e-01 absent lower incisors 5.70e-04 6.57e-01 abnormal vertebral spinous process morphology 5.71e-04 6.58e-01 absent atrioventricular cushions 5.78e-04 6.61e-01 fused phalanges 1.14e-03 9.71e-01 abnormal skeleton morphology 1.29e-03 1.00e+00 abnormal heart position or orientation 1.29e-03 1.00e+00 abnormal vertebral arch development 1.34e-03 1.00e+00 male pseudohermaphroditism 1.37e-03 1.00e+00 abnormal hard palate morphology 1.45e-03 1.00e+00 increased skeletal muscle weight

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

²FDR corrected p-value (Benjamini-Hochberg)