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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod118

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod118 Module size 74 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 9619 ABCG1 ATP binding cassette subfamily G member 1 132612 ADAD1 adenosine deaminase domain containing 1 161931 ADAD2 adenosine deaminase domain containing 2 105 ADARB2 adenosine deaminase, RNA specific B2 (inactive) 23536 ADAT1 adenosine deaminase, tRNA specific 1 338699 ANKRD42 ankyrin repeat domain 42 8312 AXIN1 axin 1 8313 AXIN2 axin 2 79184 BRCC3 BRCA1/BRCA2-containing complex subunit 3 8945 BTRC beta-transducin repeat containing E3 ubiquitin protein ligase 55049 C19orf60 required for excision 1-B domain containing 92346 C1orf105 chromosome 1 open reading frame 105 643155 C5orf43 small integral membrane protein 15 26112 CCDC69 coiled-coil domain containing 69 292071 CDT1 chromatin licensing and DNA replication factor 1 1044 CDX1 caudal type homeobox 1 1045 CDX2 caudal type homeobox 2 1046 CDX4 caudal type homeobox 4 1791 DNTT DNA nucleotidylexotransferase 7979 ECD SEM1, 26S proteasome complex subunit 641700 ECSCR endothelial cell surface expressed chemotaxis and apoptosis regulator 152756 FAM218A family with sequence similarity 218 member A 25793 FBXO7 F-box protein 7 2348 FOLR1 folate receptor 1 51343 FZR1 fizzy and cell division cycle 20 related 1 3315 HSPB1 heat shock protein family B (small) member 1 11185 INMT indolethylamine N-methyltransferase 51528 JKAMP JNK1/MAPK8 associated membrane protein 56888 KCMF1 potassium channel modulatory factor 1 59349 KLHL12 kelch like family member 12 162605 KRT28 keratin 28 353142 LCE3A late cornified envelope 3A 80774 LIMD2 LIM domain containing 2 345643 MCIN multiciliate differentiation and DNA synthesis associated cell cycle protein 114803 MYSM1 Myb like, SWIRM and MPN domains 1 374383 NCR3LG1 natural killer cell cytotoxicity receptor 3 ligand 1 55593 OTUD5 OTU deubiquitinase 5 5071 PARK2 parkin RBR E3 ubiquitin protein ligase 57095 PITHD1 PITH domain containing 1 27343 POLL DNA polymerase lambda 144165 PRICKLE1 prickle planar cell polarity protein 1 8624 PSMG1 proteasome assembly chaperone 1 56984 PSMG2 proteasome assembly chaperone 2 84262 PSMG3 proteasome assembly chaperone 3 170394 PWWP2B PWWP domain containing 2B 5886 RAD23A RAD23 homolog A, nucleotide excision repair protein 221002 RASGEF1A RasGEF domain family member 1A 64326 RFWD2 COP1, E3 ubiquitin ligase 63891 RNF123 ring finger protein 123 26278 SACS sacsin molecular chaperone 90378 SAMD1 sterile alpha motif domain containing 1 7979 SHFM1 SEM1, 26S proteasome complex subunit 6502 SKP2 S-phase kinase associated protein 2 57154 SMURF1 SMAD specific E3 ubiquitin protein ligase 1 10617 STAMBP STAM binding protein 57559 STAMBPL1 STAM binding protein like 1 94056 SYAP1 synapse associated protein 1 55623 THUMPD1 THUMP domain containing 1 8658 TNKS tankyrase 80351 TNKS2 tankyrase 2 9352 TXNL1 thioredoxin like 1 10422 UBAC1 UBA domain containing 1 7314 UBB ubiquitin B 11065 UBE2C ubiquitin conjugating enzyme E2 C 7324 UBE2E1 ubiquitin conjugating enzyme E2 E1 89910 UBE3B ubiquitin protein ligase E3B 90025 UBE3D ubiquitin protein ligase E3D 134510 UBLCP1 ubiquitin like domain containing CTD phosphatase 1 51377 UCHL5 ubiquitin C-terminal hydrolase L5 9100 USP10 ubiquitin specific peptidase 10 79446 WDR25 WD repeat domain 25 126820 WDR63 WD repeat domain 63 7466 WFS1 wolframin ER transmembrane glycoprotein 55596 ZCCHC8 zinc finger CCHC-type containing 8

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 5.89e-01 1.28e-05 Reactome XAV939 inhibits tankyrase, stabilizing AXIN Disease 4.46e-01 3.61e-03 Reactome Methylation of MeSeH for excretion Metabolism 3.77e-01 3.61e-03 Reactome Deletions in the AXIN genes in hepatocellular carcinoma result in elevated WNT signaling Disease 1.76e-01 8.89e-07 GO adenosine deaminase activity molecular_function 1.51e-01 8.89e-07 GO double-stranded RNA adenosine deaminase activity molecular_function 1.45e-01 7.45e-08 GO Lys63-specific deubiquitinase activity molecular_function 1.11e-01 1.50e-07 GO proteasome binding molecular_function 7.29e-02 7.24e-06 GO I-SMAD binding molecular_function 4.87e-02 9.63e-06 Reactome Josephin domain DUBs Metabolism of proteins 4.28e-02 1.55e-06 GO adenosine to inosine editing biological_process 3.22e-02 8.22e-08 Reactome Metalloprotease DUBs Metabolism of proteins 2.91e-02 4.16e-05 Reactome Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase Cell Cycle 1.46e-02 2.43e-05 GO regulation of proteasomal protein catabolic process biological_process 8.06e-03 5.66e-04 GO proteasome assembly biological_process 4.42e-03 6.06e-11 Reactome Antigen processing: Ubiquitination & Proteasome degradation Immune System 4.24e-03 8.27e-04 GO positive regulation of ubiquitin protein ligase activity biological_process 3.23e-04 2.53e-15 Reactome Deubiquitination Metabolism of proteins

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 protein deubiquitination 0.00e+00 0.00e+00 protein modification by small protein removal 1.78e-09 1.28e-06 ubiquitin-dependent protein catabolic process 2.13e-09 1.52e-06 modification-dependent protein catabolic process 4.58e-09 1.90e-06 proteasome complex 7.87e-09 5.18e-06 proteolysis involved in cellular protein catabolic process 1.38e-08 8.84e-06 positive regulation of protein ubiquitination 1.49e-08 9.49e-06 proteasome-mediated ubiquitin-dependent protein catabolic process 1.63e-08 1.03e-05 cellular protein catabolic process 1.77e-08 1.12e-05 positive regulation of proteolysis involved in cellular protein catabolic process 2.12e-08 1.32e-05 proteasomal protein catabolic process 3.59e-08 2.17e-05 positive regulation of cellular protein catabolic process 4.49e-08 2.68e-05 protein ubiquitination 4.87e-08 2.89e-05 protein catabolic process 9.55e-08 3.68e-05 adenosine deaminase activity 1.39e-07 7.66e-05 regulation of protein catabolic process 1.46e-07 8.01e-05 protein modification by small protein conjugation 1.92e-07 1.03e-04 protein polyubiquitination 2.80e-07 1.47e-04 regulation of protein ubiquitination 4.49e-07 2.28e-04 positive regulation of protein catabolic process

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 1.31e-06 2.23e-04 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 1.40e-06 3.09e-04 ANTIGEN PROCESSING UBIQUITINATION PROTEASOME DEGRADATION 3.45e-06 5.53e-04 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 4.52e-06 9.12e-04 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION 9.00e-04 1.07e-01 REGULATION OF MITOTIC CELL CYCLE 1.33e-03 1.29e-01 REGULATION OF MITOTIC CELL CYCLE 2.69e-03 2.41e-01 DOWNREGULATION OF TGF BETA RECEPTOR SIGNALING 3.73e-03 3.20e-01 TGF BETA RECEPTOR SIGNALING ACTIVATES SMADS 4.62e-03 4.28e-01 DOWNREGULATION OF TGF BETA RECEPTOR SIGNALING 5.19e-03 4.23e-01 CONVERSION FROM APC C CDC20 TO APC C CDH1 IN LATE ANAPHASE 5.57e-03 4.99e-01 APC C CDH1 MEDIATED DEGRADATION OF CDC20 AND OTHER APC C CDH1 TARGETED PROTEINS IN LATE MITOSIS EARLY G1 5.87e-03 4.70e-01 PHOSPHORYLATION OF THE APC C 5.89e-03 4.72e-01 INHIBITION OF THE PROTEOLYTIC ACTIVITY OF APC C REQUIRED FOR THE ONSET OF ANAPHASE BY MITOTIC SPINDLE CHECKPOINT COMPONENTS 6.26e-03 5.50e-01 TGF BETA RECEPTOR SIGNALING ACTIVATES SMADS 6.43e-03 5.62e-01 CONVERSION FROM APC C CDC20 TO APC C CDH1 IN LATE ANAPHASE 7.35e-03 6.25e-01 PHOSPHORYLATION OF THE APC C 7.74e-03 5.95e-01 APC C CDC20 MEDIATED DEGRADATION OF CYCLIN B 7.75e-03 5.95e-01 APC CDC20 MEDIATED DEGRADATION OF NEK2A 8.48e-03 6.42e-01 APC C CDH1 MEDIATED DEGRADATION OF CDC20 AND OTHER APC C CDH1 TARGETED PROTEINS IN LATE MITOSIS EARLY G1 8.54e-03 7.07e-01 APC C CDC20 MEDIATED DEGRADATION OF CYCLIN B

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.03e-04 2.31e-01 absent ribs 1.29e-04 2.68e-01 kinked tail 7.57e-04 7.65e-01 short tail 8.53e-04 8.23e-01 absent trophoblast giant cells 1.24e-03 1.00e+00 thoracic vertebral transformation 1.64e-03 1.00e+00 increased oxygen consumption 1.78e-03 1.00e+00 cardia bifida 2.31e-03 1.00e+00 absent forebrain 2.32e-03 1.00e+00 abnormal tail morphology 3.06e-03 1.00e+00 hippocampal neuron degeneration 3.56e-03 1.00e+00 abnormal mitotic spindle morphology 4.79e-03 1.00e+00 increased coping response 5.88e-03 1.00e+00 increased body temperature 7.06e-03 1.00e+00 increased fibroblast apoptosis 7.39e-03 1.00e+00 fusion of vertebral arches 8.31e-03 1.00e+00 abnormal embryonic erythropoiesis 8.32e-03 1.00e+00 increased mean corpuscular hemoglobin 8.93e-03 1.00e+00 shortened head 1.16e-02 1.00e+00 cervical vertebral transformation 1.23e-02 1.00e+00 increased red blood cell distribution width

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

²FDR corrected p-value (Benjamini-Hochberg)