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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod280

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod280 Module size 34 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 431705 ASTL astacin like metalloendopeptidase 9210 BMP15 bone morphogenetic protein 15 651 BMP3 bone morphogenetic protein 3 91653 BOC BOC cell adhesion associated, oncogene regulated 199699 DAND5 DAN domain BMP antagonist family member 5 293823 DHH prune homolog 2 84976 DISP1 dispatched RND transporter family member 1 85455 DISP2 dispatched RND transporter family member 2 64641 EBF2 early B cell factor 2 22924 EBF3 microtubule associated protein RP/EB family member 3 2619 GAS1 growth arrest specific 1 2657 GDF1 growth differentiation factor 1 2662 GDF10 growth differentiation factor 10 10220 GDF11 growth differentiation factor 11 9518 GDF15 growth differentiation factor 15 2658 GDF2 growth differentiation factor 2 9573 GDF3 growth differentiation factor 3 2661 GDF9 growth differentiation factor 9 57211 GPR126 adhesion G protein-coupled receptor G6 3549 IHH indian hedgehog 10637 LEFTY1 left-right determination factor 1 2660 MSTN myostatin 5727 PTCH1 patched 1 8643 PTCH2 patched 2 6469 SHH sonic hedgehog 6608 SMO smoothened, frizzled class receptor 27148 STK36 serine/threonine kinase 36 10716 TBR1 T-box, brain 1 6926 TBX3 T-box 3 6910 TBX5 T-box 5 6911 TBX6 T-box 6 54986 ULK4 unc-51 like kinase 4 117166 WFIKKN1 WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 1 124857 WFIKKN2 WAP, follistatin/kazal, immunoglobulin, kunitz and netrin 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 3.69e-01 8.68e-16 Reactome Ligand-receptor interactions Signal Transduction 1.75e-01 1.06e-12 GO patched binding molecular_function 7.60e-02 7.86e-10 Reactome Release of Hh-Np from the secreting cell Signal Transduction 6.85e-02 8.33e-22 GO transforming growth factor beta receptor binding molecular_function 5.57e-02 8.46e-23 GO regulation of MAPK cascade biological_process 5.54e-02 6.46e-09 Reactome HHAT G278V abrogates palmitoylation of Hh-Np Disease 4.22e-02 3.01e-23 GO cell development biological_process 3.47e-02 4.37e-21 GO positive regulation of pathway-restricted SMAD protein phosphorylation biological_process 3.06e-02 2.25e-07 Reactome GLI proteins bind promoters of Hh responsive genes to promote transcription Signal Transduction 2.82e-02 1.60e-04 GO extracellular negative regulation of signal transduction biological_process 1.84e-02 1.07e-05 GO hedgehog family protein binding molecular_function 1.70e-02 1.95e-04 GO muscle fiber development biological_process 1.25e-02 1.60e-04 GO forelimb morphogenesis biological_process 9.31e-03 3.56e-06 GO cell fate determination biological_process 8.79e-03 1.60e-04 GO somite rostral/caudal axis specification biological_process 5.23e-03 4.35e-20 GO SMAD protein signal transduction biological_process 3.63e-03 3.21e-15 GO smoothened 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 regulation of pathway-restricted SMAD protein phosphorylation 0.00e+00 0.00e+00 SMAD protein signal transduction 0.00e+00 0.00e+00 transmembrane receptor protein serine/threonine kinase signaling pathway 0.00e+00 0.00e+00 positive regulation of pathway-restricted SMAD protein phosphorylation 0.00e+00 0.00e+00 smoothened signaling pathway 0.00e+00 0.00e+00 growth factor activity 0.00e+00 0.00e+00 transforming growth factor beta receptor binding 0.00e+00 0.00e+00 cytokine activity 1.46e-11 9.59e-09 patched binding 2.96e-11 1.90e-08 cytokine receptor binding 7.42e-11 6.25e-08 regulation of smoothened signaling pathway 1.63e-09 1.18e-06 pattern specification process 3.76e-09 2.59e-06 BMP signaling pathway 9.50e-09 6.19e-06 cellular response to BMP stimulus 2.84e-08 1.74e-05 positive regulation of smoothened signaling pathway 3.34e-07 1.73e-04 determination of left/right symmetry 3.49e-07 1.80e-04 positive regulation of hh target transcription factor activity 4.19e-07 2.13e-04 determination of bilateral symmetry 4.24e-07 2.16e-04 embryonic pattern specification 6.26e-07 3.10e-04 cell fate commitment

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 8.57e-09 2.54e-06 CLASS B 2 SECRETIN FAMILY RECEPTORS 4.63e-06 7.32e-04 CLASS B 2 SECRETIN FAMILY RECEPTORS 1.63e-04 2.40e-02 GPCR LIGAND BINDING 6.28e-04 7.84e-02 SIGNALING BY NODAL 6.98e-03 5.46e-01 SIGNALING BY NODAL 2.90e-02 1.00e+00 DEVELOPMENTAL BIOLOGY 3.30e-02 1.00e+00 YAP1 AND WWTR1 TAZ STIMULATED GENE EXPRESSION 3.79e-02 1.00e+00 YAP1 AND WWTR1 TAZ STIMULATED GENE EXPRESSION 4.24e-02 1.00e+00 MYOGENESIS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.52e-06 1.19e-02 annular pancreas 1.47e-04 2.92e-01 abnormal direction of embryo turning 2.83e-04 4.36e-01 abnormal left-right axis patterning 2.85e-04 4.37e-01 dermal hyperplasia 3.11e-04 4.59e-01 abnormal digit morphology 6.46e-04 7.03e-01 thin apical ectodermal ridge 7.36e-04 7.59e-01 abnormal sinus arrhythmia 7.98e-04 7.91e-01 abnormal optic vesicle formation 8.33e-04 8.12e-01 atrial septal defect 8.99e-04 8.46e-01 brachyphalangia 9.42e-04 8.72e-01 situs inversus 1.28e-03 1.00e+00 abnormal digestive organ placement 1.29e-03 1.00e+00 abnormal phalanx morphology 1.50e-03 1.00e+00 fused first pharyngeal arch 1.61e-03 1.00e+00 abnormal digestive system morphology 1.79e-03 1.00e+00 decreased quadriceps weight 1.89e-03 1.00e+00 impaired skeletal muscle regeneration 2.91e-03 1.00e+00 oligodactyly 3.21e-03 1.00e+00 small olfactory bulb 3.54e-03 1.00e+00 failure of heart looping

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

²FDR corrected p-value (Benjamini-Hochberg)