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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod67

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod67 Module size 81 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 92714 ARRDC1 arrestin domain containing 1 27106 ARRDC2 arrestin domain containing 2 57561 ARRDC3 arrestin domain containing 3 91947 ARRDC4 arrestin domain containing 4 645432 ARRDC5 arrestin domain containing 5 25923 ATL3 atlastin GTPase 3 9531 BAG3 BCL2 associated athanogene 3 1184 CLCN5 chloride voltage-gated channel 5 10404 CPQ carboxypeptidase Q 23033 DOPEY1 DOP1 leucine zipper like protein A 9980 DOPEY2 DOP1 leucine zipper like protein B 23220 DTX4 deltex E3 ubiquitin ligase 4 79956 ERMP1 endoplasmic reticulum metallopeptidase 1 2086 ERV3-1 endogenous retrovirus group 3 member 1, envelope 9413 FAM189A2 family with sequence similarity 189 member A2 57600 FNIP2 folliculin interacting protein 2 25831 HECTD1 HECT domain E3 ubiquitin protein ligase 1 143279 HECTD2 HECT domain E3 ubiquitin protein ligase 2 79654 HECTD3 HECT domain E3 ubiquitin protein ligase 3 57520 HECW2 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 8916 HERC3 HECT and RLD domain containing E3 ubiquitin protein ligase 3 26091 HERC4 HECT and RLD domain containing E3 ubiquitin protein ligase 4 55008 HERC6 HECT and RLD domain containing E3 ubiquitin protein ligase family member 6 83737 ITCH itchy E3 ubiquitin protein ligase 9870 KIAA0317 apoptosis resistant E3 ubiquitin protein ligase 1 84162 KIAA1109 KIAA1109 9516 LITAF lipopolysaccharide induced TNF factor 66004 LYNX1 Ly6/neurotoxin 1 9223 MAGI1 membrane associated guanylate kinase, WW and PDZ domain containing 1 260425 MAGI3 membrane associated guanylate kinase, WW and PDZ domain containing 3 79917 MAGIX MAGI family member, X-linked 254528 MEIOB meiosis specific with OB domains 23295 MGRN1 mahogunin ring finger 1 2315 MLANA melan-A 10003 NAALAD2 N-acetylated alpha-linked acidic dipeptidase 2 10004 NAALADL1 N-acetylated alpha-linked acidic dipeptidase like 1 254827 NAALADL2 N-acetylated alpha-linked acidic dipeptidase like 2 80762 NDFIP1 Nedd4 family interacting protein 1 54602 NDFIP2 Nedd4 family interacting protein 2 4734 NEDD4 neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase 23327 NEDD4L neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase 113791 PIK3IP1 phosphoinositide-3-kinase interacting protein 1 5639 PRRG2 proline rich and Gla domain 2 10067 SCAMP3 secretory carrier membrane protein 3 6556 SLC11A1 solute carrier family 11 member 1 353189 SLCO4C1 solute carrier organic anion transporter family member 4C1 64750 SMURF2 SMAD specific E3 ubiquitin protein ligase 2 23111 SPG20 spartin 8027 STAM signal transducing adaptor molecule 10254 STAM2 signal transducing adaptor molecule 2 9287 TAAR2 trace amine associated receptor 2 (gene/pseudogene) 132001 TAMM41 TAM41 mitochondrial translocator assembly and maintenance homolog 7036 TFR2 transferrin receptor 2 9320 TRIP12 thyroid hormone receptor interactor 12 10628 TXNIP thioredoxin interacting protein 7337 UBE3A ubiquitin protein ligase E3A 9690 UBE3C ubiquitin protein ligase E3C 197131 UBR1 ubiquitin protein ligase E3 component n-recognin 1 9099 USP2 ubiquitin specific peptidase 2 27005 USP21 ubiquitin specific peptidase 21 23358 USP24 ubiquitin specific peptidase 24 29761 USP25 ubiquitin specific peptidase 25 83844 USP26 ubiquitin specific peptidase 26 57646 USP28 ubiquitin specific peptidase 28 57663 USP29 ubiquitin specific peptidase 29 57695 USP37 ubiquitin specific peptidase 37 55230 USP40 ubiquitin specific peptidase 40 124739 USP43 ubiquitin specific peptidase 43 84196 USP48 ubiquitin specific peptidase 48 8078 USP5 ubiquitin specific peptidase 5 373509 USP50 ubiquitin specific peptidase 50 8287 USP9Y ubiquitin specific peptidase 9 Y-linked 1650 WBP1 dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit 23558 WBP2 WW domain binding protein 2 164684 WBP2NL WBP2 N-terminal like 23286 WWC1 WW and C2 domain containing 1 80014 WWC2 WW and C2 domain containing 2 51741 WWOX WW domain containing oxidoreductase 11059 WWP1 WW domain containing E3 ubiquitin protein ligase 1 11060 WWP2 WW domain containing E3 ubiquitin protein ligase 2 10413 YAP1 Yes associated protein 1

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 1.40e-01 3.90e-06 Reactome Downregulation of ERBB4 signaling Signal Transduction 1.17e-01 5.83e-06 GO negative regulation of sodium ion transmembrane transporter activity biological_process 6.12e-02 8.92e-14 GO thiol-dependent ubiquitinyl hydrolase activity molecular_function 6.01e-02 1.75e-07 GO WW domain binding molecular_function 5.90e-02 4.77e-04 GO negative regulation of hippo signaling biological_process 4.71e-02 3.80e-05 GO carboxypeptidase activity molecular_function 2.58e-02 7.72e-10 GO positive regulation of protein catabolic process biological_process 2.46e-02 7.63e-04 GO positive regulation of intracellular estrogen receptor signaling pathway biological_process 2.20e-02 1.20e-05 GO response to progesterone biological_process 1.69e-02 7.63e-04 GO dipeptidase activity molecular_function 1.54e-02 7.76e-15 Reactome Antigen processing: Ubiquitination & Proteasome degradation Immune System 1.32e-02 7.63e-04 GO arrestin family protein binding molecular_function 1.24e-02 1.11e-03 GO iron ion transport 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 ubiquitinyl hydrolase activity 0.00e+00 0.00e+00 cysteine-type peptidase activity 0.00e+00 0.00e+00 thiol-dependent ubiquitinyl hydrolase activity 2.17e-19 2.08e-16 ubiquitin-dependent protein catabolic process 3.02e-19 2.90e-16 modification-dependent protein catabolic process 2.92e-18 2.79e-15 proteolysis involved in cellular protein catabolic process 8.37e-18 7.96e-15 cellular protein catabolic process 6.81e-17 6.45e-14 protein catabolic process 1.77e-14 1.66e-11 protein deubiquitination 5.21e-14 4.88e-11 protein modification by small protein removal 1.26e-11 8.32e-09 ubiquitin-protein transferase activity 1.40e-11 1.25e-08 protein ubiquitination 2.48e-11 1.60e-08 ubiquitin-like protein transferase activity 1.09e-10 9.00e-08 protein modification by small protein conjugation 1.70e-10 1.01e-07 peptidase activity 6.04e-09 2.83e-06 thiol-dependent ubiquitin-specific protease activity 9.12e-08 5.18e-05 protein polyubiquitination 3.94e-06 1.67e-03 negative regulation of transporter activity 4.20e-06 1.18e-03 ubiquitin protein ligase activity 1.01e-05 2.63e-03 WW domain binding

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 4.46e-09 1.35e-06 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 3.26e-08 8.96e-06 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 3.20e-07 5.91e-05 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 7.66e-07 1.35e-04 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 1.14e-06 1.96e-04 SIGNALING BY ERBB4 4.07e-06 8.27e-04 SIGNALING BY ERBB4 5.47e-04 6.96e-02 EGFR DOWNREGULATION 5.80e-04 6.18e-02 SIGNALING BY HIPPO 1.35e-03 1.31e-01 EGFR DOWNREGULATION 1.37e-03 1.54e-01 SIGNALING BY EGFR IN CANCER 1.69e-03 1.85e-01 SIGNALING BY HIPPO 2.06e-03 1.91e-01 NUCLEAR SIGNALING BY ERBB4 2.36e-03 2.15e-01 SIGNALING BY EGFR IN CANCER 2.96e-03 2.97e-01 ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT ESCRT 3.44e-03 3.35e-01 NUCLEAR SIGNALING BY ERBB4 8.00e-03 6.12e-01 ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT ESCRT 2.49e-02 1.00e+00 TRANSPORT OF ORGANIC ANIONS 2.99e-02 1.00e+00 THE NLRP3 INFLAMMASOME 3.78e-02 1.00e+00 INFLAMMASOMES 3.83e-02 1.00e+00 DOWNREGULATION OF SMAD2 3 SMAD4 TRANSCRIPTIONAL ACTIVITY

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.98e-04 3.47e-01 increased circulating potassium level 4.10e-04 5.37e-01 increased circulating ketone body level 6.67e-04 7.18e-01 decreased circulating total protein level 6.89e-04 7.30e-01 hypoglycemia 1.71e-03 1.00e+00 decreased spleen weight 1.87e-03 1.00e+00 abnormal tail morphology 3.29e-03 1.00e+00 brain vacuoles 3.96e-03 1.00e+00 decreased circulating triglyceride level 4.67e-03 1.00e+00 decreased circulating sodium level 5.56e-03 1.00e+00 increased circulating iron level 6.14e-03 1.00e+00 decreased blood urea nitrogen level 6.27e-03 1.00e+00 abnormal iron homeostasis 9.01e-03 1.00e+00 decreased thymus weight 1.09e-02 1.00e+00 decreased gonadal fat pad weight 1.42e-02 1.00e+00 increased blood urea nitrogen level 1.48e-02 1.00e+00 decreased leukocyte cell number 1.49e-02 1.00e+00 enhanced passive avoidance behavior 1.49e-02 1.00e+00 ascending aorta hypoplasia 1.49e-02 1.00e+00 abnormal circadian period 1.52e-02 1.00e+00 reduced male fertility

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

²FDR corrected p-value (Benjamini-Hochberg)