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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod137

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod137 Module size 72 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 102 ADAM10 ADAM metallopeptidase domain 10 6868 ADAM17 ADAM metallopeptidase domain 17 9068 ANGPTL1 angiopoietin like 1 83854 ANGPTL6 angiopoietin like 6 10218 ANGPTL7 angiopoietin like 7 51107 APH1A aph-1 homolog A, gamma-secretase subunit 83464 APH1B aph-1 homolog B, gamma-secretase subunit 54825 CDHR2 cadherin related family member 2 653275 CFC1B cripto, FRL-1, cryptic family 1B 23418 CRB1 crumbs 1, cell polarity complex component 286204 CRB2 crumbs 2, cell polarity complex component 9231 DLG5 discs large MAGUK scaffold protein 5 8788 DLK1 delta like non-canonical Notch ligand 1 28514 DLL1 delta like canonical Notch ligand 1 10683 DLL3 delta like canonical Notch ligand 3 54567 DLL4 delta like canonical Notch ligand 4 92737 DNER delta/notch like EGF repeat containing 1840 DTX1 deltex E3 ubiquitin ligase 1 113878 DTX2 deltex E3 ubiquitin ligase 2 51162 EGFL7 EGF like domain multiple 7 57669 EPB41L5 erythrocyte membrane protein band 4.1 like 5 346007 EYS eyes shut homolog 129804 FBLN7 fibulin 7 84929 FIBCD1 fibrinogen C domain containing 1 143162 FRMPD2 FERM and PDZ domain containing 2 160622 GRASP general receptor for phosphoinositides 1 associated scaffold protein 392862 GRID2IP Grid2 interacting protein 10499 GRIP1 nuclear receptor coactivator 2 3083 HGFAC HGF activator 256158 HMCN2 hemicentin 2 3603 IL16 interleukin 16 182 JAG1 jagged 1 3714 JAG2 jagged 2 84623 KIRREL3 kirre like nephrin family adhesion molecule 3 3955 LFNG LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 4052 LTBP1 latent transforming growth factor beta binding protein 1 8425 LTBP4 latent transforming growth factor beta binding protein 4 153562 MARVELD2 MARVEL domain containing 2 4148 MATN3 matrilin 3 4242 MFNG MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 23385 NCSTN nicastrin 9148 NEURL neuralized E3 ubiquitin protein ligase 1 54492 NEURL1B neuralized E3 ubiquitin protein ligase 1B 4851 NOTCH1 notch 1 4853 NOTCH2 notch 2 4854 NOTCH3 notch 3 4855 NOTCH4 notch 4 9253 NUMBL NUMB like, endocytic adaptor protein 117583 PARD3B par-3 family cell polarity regulator beta 23037 PDZD2 PDZ domain containing 2 440107 PLEKHG7 pleckstrin homology and RhoGEF domain containing G7 84898 PLXDC2 plexin domain containing 2 23509 POFUT1 protein O-fucosyltransferase 1 56983 POGLUT1 protein O-glucosyltransferase 1 5663 PSEN1 presenilin 1 5664 PSEN2 presenilin 2 55851 PSENEN presenilin enhancer, gamma-secretase subunit 5949 RBP3 retinol binding protein 3 5986 RFNG RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 55206 SBNO1 strawberry notch homolog 1 22904 SBNO2 strawberry notch homolog 2 80274 SCUBE1 signal peptide, CUB domain and EGF like domain containing 1 57758 SCUBE2 signal peptide, CUB domain and EGF like domain containing 2 222663 SCUBE3 signal peptide, CUB domain and EGF like domain containing 3 340146 SLC35D3 solute carrier family 35 member D3 25992 SNED1 sushi, nidogen and EGF like domains 1 79987 SVEP1 sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 7007 TECTA tectorin alpha 10083 USH1C USH1 protein network component harmonin 245806 VGLL2 vestigial like family member 2 64856 VWA1 von Willebrand factor A domain containing 1 220001 VWCE von Willebrand factor C and EGF domains

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 4.76e-01 3.07e-15 Reactome Pre-NOTCH Processing in the Endoplasmic Reticulum Signal Transduction 2.83e-01 4.73e-25 Reactome NOTCH4 Activation and Transmission of Signal to the Nucleus Signal Transduction 2.22e-01 9.67e-37 Reactome Activated NOTCH1 Transmits Signal to the Nucleus Signal Transduction 1.48e-01 1.55e-08 GO protein O-linked fucosylation biological_process 1.48e-01 1.11e-17 Reactome Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant Disease 1.40e-01 1.11e-17 Reactome Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant Disease 1.35e-01 1.76e-18 GO Notch receptor processing biological_process 1.25e-01 8.65e-15 Reactome Pre-NOTCH Processing in Golgi Signal Transduction 9.86e-02 6.49e-10 GO regulation of Notch signaling pathway biological_process 7.69e-02 8.85e-17 Reactome Noncanonical activation of NOTCH3 Signal Transduction 6.79e-02 1.11e-17 GO Notch receptor processing, ligand-dependent biological_process 5.21e-02 6.58e-17 GO Notch binding molecular_function 2.09e-03 2.23e-04 GO positive regulation of 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 Notch signaling pathway 0.00e+00 0.00e+00 Notch receptor processing 0.00e+00 0.00e+00 Notch signaling pathway 0.00e+00 0.00e+00 positive regulation of Notch signaling pathway 0.00e+00 0.00e+00 Notch binding 6.96e-20 5.00e-17 calcium ion binding 2.67e-11 2.34e-08 membrane protein proteolysis 3.38e-11 2.94e-08 membrane protein ectodomain proteolysis 1.23e-10 6.26e-08 gamma-secretase complex 1.04e-09 7.74e-07 amyloid precursor protein catabolic process 1.64e-09 1.19e-06 membrane protein intracellular domain proteolysis 6.80e-09 4.51e-06 beta-amyloid formation 6.83e-09 4.53e-06 somitogenesis 7.98e-09 5.24e-06 amyloid precursor protein metabolic process 1.90e-08 1.19e-05 beta-amyloid metabolic process 2.13e-08 1.33e-05 compartment pattern specification 5.19e-08 3.07e-05 somite development 1.11e-07 6.23e-05 segmentation 1.40e-07 5.27e-05 O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity 1.57e-07 8.57e-05 marginal zone B cell differentiation

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 RECEPTOR LIGAND BINDING INITIATES THE SECOND PROTEOLYTIC CLEAVAGE OF NOTCH RECEPTOR 0.00e+00 0.00e+00 SIGNALING BY NOTCH 0.00e+00 0.00e+00 SIGNALING BY NOTCH4 0.00e+00 0.00e+00 SIGNALING BY NOTCH1 0.00e+00 0.00e+00 SIGNALING BY NOTCH3 0.00e+00 0.00e+00 SIGNALING BY NOTCH2 0.00e+00 0.00e+00 ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS 0.00e+00 0.00e+00 REGULATED PROTEOLYSIS OF P75NTR 0.00e+00 0.00e+00 RECEPTOR LIGAND BINDING INITIATES THE SECOND PROTEOLYTIC CLEAVAGE OF NOTCH RECEPTOR 0.00e+00 0.00e+00 SIGNALING BY NOTCH4 0.00e+00 0.00e+00 SIGNALING BY NOTCH 0.00e+00 0.00e+00 SIGNALING BY NOTCH1 0.00e+00 0.00e+00 SIGNALING BY NOTCH3 0.00e+00 0.00e+00 SIGNALING BY NOTCH2 0.00e+00 0.00e+00 ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS 0.00e+00 0.00e+00 REGULATED PROTEOLYSIS OF P75NTR 2.23e-10 7.87e-08 NRIF SIGNALS CELL DEATH FROM THE NUCLEUS 2.33e-10 8.18e-08 PRE NOTCH EXPRESSION AND PROCESSING 2.52e-10 6.59e-08 PRE NOTCH EXPRESSION AND PROCESSING 1.42e-09 4.61e-07 PRE NOTCH PROCESSING IN GOLGI

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.48e-08 3.43e-04 abnormal somite development 1.05e-06 9.09e-03 abnormal somite shape 1.30e-06 1.06e-02 abnormal somite size 2.18e-06 1.56e-02 abnormal vitelline vasculature morphology 3.52e-06 2.24e-02 fused dorsal root ganglion 1.13e-05 5.11e-02 abnormal sclerotome morphology 2.03e-05 7.66e-02 distended pericardium 2.65e-05 9.48e-02 kinked neural tube 3.61e-05 1.15e-01 abnormal vascular development 4.99e-05 1.42e-01 absent intersomitic vessels 1.00e-04 2.26e-01 abnormal blood vessel morphology 1.07e-04 2.37e-01 abnormal rostral-caudal patterning of the somites 1.24e-04 2.59e-01 caudal body truncation 1.66e-04 3.13e-01 abnormal dorsal-ventral polarity of the somites 3.53e-04 4.92e-01 decreased body length 5.95e-04 6.72e-01 decreased axial mesoderm size 6.17e-04 6.83e-01 rib fusion 7.47e-04 7.62e-01 abnormal neural tube morphology/development 9.25e-04 8.63e-01 decreased transforming growth factor level 1.46e-03 1.00e+00 short tail

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

²FDR corrected p-value (Benjamini-Hochberg)