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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod151

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod151 Module size 52 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 328 APEX1 apurinic/apyrimidinic endodeoxyribonuclease 1 27301 APEX2 apurinic/apyrimidinic endodeoxyribonuclease 2 200558 APLF aprataxin and PNKP like factor 54840 APTX aprataxin 64421 DCLRE1C DNA cross-link repair 1C 2067 ERCC1 ERCC excision repair 1, endonuclease non-catalytic subunit 302982 ERCC4 essential meiotic structure-specific endonuclease subunit 2 22909 FAN1 FANCD2 and FANCI associated nuclease 1 340533 KIAA2022 neurite extension and migration factor 3980 LIG3 DNA ligase 3 3981 LIG4 DNA ligase 4 4292 MLH1 mutL homolog 1 27030 MLH3 mutL homolog 3 4436 MSH2 mutS homolog 2 4437 MSH3 mutS homolog 3 4438 MSH4 mutS homolog 4 4439 MSH5 mutS homolog 5 100532732 MSH5-SAPCD1 MSH5-SAPCD1 readthrough (NMD candidate) 2956 MSH6 mutS homolog 6 79661 NEIL1 nei like DNA glycosylase 1 79840 NHEJ1 non-homologous end joining factor 1 4968 OGG1 8-oxoguanine DNA glycosylase 5111 PCNA proliferating cell nuclear antigen 5378 PMS1 PMS1 homolog 1, mismatch repair system component 5395 PMS2 PMS1 homolog 2, mismatch repair system component 11284 PNKP polynucleotide kinase 3'-phosphatase 5424 POLD1 DNA polymerase delta 1, catalytic subunit 5425 POLD2 DNA polymerase delta 2, accessory subunit 10714 POLD3 DNA polymerase delta 3, accessory subunit 57804 POLD4 DNA polymerase delta 4, accessory subunit 5426 POLE DNA polymerase epsilon, catalytic subunit 56655 POLE4 DNA polymerase epsilon 4, accessory subunit 5428 POLG DNA polymerase gamma, catalytic subunit 5429 POLH DNA polymerase eta 11201 POLI DNA polymerase iota 11044 POLK terminal nucleotidyltransferase 4A 27434 POLM DNA polymerase mu 353497 POLN DNA polymerase nu 51455 REV1 REV1, DNA directed polymerase 5980 REV3L REV3 like, DNA directed polymerase zeta catalytic subunit 89809 RFC1 replication factor C subunit 1 126074 SWSAP1 SWIM-type zinc finger 7 associated protein 1 55775 TDP1 tyrosyl-DNA phosphodiesterase 1 7374 UNG uracil DNA glycosylase 7507 XPA XPA, DNA damage recognition and repair factor 7508 XPC XPC complex subunit, DNA damage recognition and repair factor 7515 XRCC1 X-ray repair cross complementing 1 309995 XRCC4 X-ray repair cross complementing 4 7520 XRCC5 X-ray repair cross complementing 5 2547 XRCC6 X-ray repair cross complementing 6 91419 XRCC6BP1 ATP23 metallopeptidase and ATP synthase assembly factor homolog 125150 ZSWIM7 zinc finger SWIM-type containing 7

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 4.30e-01 1.09e-14 GO nonhomologous end joining complex cellular_component 2.79e-01 3.92e-16 GO guanine/thymine mispair binding molecular_function 2.55e-01 2.74e-15 GO mismatched DNA binding molecular_function 2.39e-01 5.27e-27 GO DNA-directed DNA polymerase activity molecular_function 2.35e-01 3.20e-12 Reactome APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway DNA Repair 1.99e-01 4.34e-07 GO phosphodiesterase I activity molecular_function 1.81e-01 1.14e-20 GO mismatch repair complex cellular_component 1.43e-01 3.82e-11 GO single strand break repair biological_process 1.16e-01 8.71e-08 GO DNA ligase activity molecular_function 1.08e-01 2.17e-47 GO damaged DNA binding molecular_function 1.08e-01 7.97e-06 Reactome Defective Mismatch Repair Associated With MLH1 Disease 1.07e-01 3.82e-11 GO class I DNA-(apurinic or apyrimidinic site) endonuclease activity molecular_function 1.07e-01 7.97e-06 Reactome Defective Mismatch Repair Associated With PMS2 Disease 4.78e-02 1.73e-22 GO nucleotide-excision repair, DNA incision biological_process 4.71e-02 3.98e-23 Reactome Mismatch Repair DNA Repair 4.71e-02 1.12e-24 Reactome Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template DNA Repair 4.28e-02 1.21e-06 GO single-stranded DNA endodeoxyribonuclease activity molecular_function 3.87e-02 1.46e-23 Reactome Termination of translesion DNA synthesis DNA Repair 3.37e-02 4.06e-09 GO establishment of integrated proviral latency biological_process 1.92e-02 9.20e-30 Reactome Base Excision Repair DNA Repair 1.76e-02 9.20e-30 Reactome Resolution of Abasic Sites (AP sites) DNA Repair 1.59e-02 1.14e-20 Reactome Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) DNA Repair 1.56e-02 1.14e-20 Reactome Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) DNA Repair 1.49e-02 1.74e-07 GO 3'-5' exonuclease activity molecular_function 9.22e-03 7.58e-62 Reactome DNA Repair DNA Repair 4.59e-03 1.16e-12 Reactome Polymerase switching Cell Cycle#DNA Replication 4.29e-03 1.16e-12 Reactome Leading Strand Synthesis Cell Cycle#DNA Replication 4.08e-03 4.71e-06 GO UV-damage excision repair biological_process 3.46e-03 1.16e-12 Reactome Polymerase switching on the C-strand of the telomere Cell Cycle 3.09e-03 1.32e-22 Reactome Gap-filling DNA repair synthesis and ligation in GG-NER DNA Repair 3.34e-04 2.83e-04 GO TFIID-class transcription factor binding molecular_function

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 DNA repair 0e+00 0e+00 base-excision repair 0e+00 0e+00 response to radiation 0e+00 0e+00 nucleotide-excision repair 0e+00 0e+00 nucleic acid phosphodiester bond hydrolysis 0e+00 0e+00 cellular response to DNA damage stimulus 0e+00 0e+00 DNA metabolic process 0e+00 0e+00 nucleotide-excision repair, DNA incision 0e+00 0e+00 mismatch repair 0e+00 0e+00 DNA recombination 0e+00 0e+00 DNA replication 0e+00 0e+00 DNA-dependent DNA replication 0e+00 0e+00 DNA biosynthetic process 0e+00 0e+00 double-strand break repair 0e+00 0e+00 DNA ligation 0e+00 0e+00 transcription-coupled nucleotide-excision repair 0e+00 0e+00 double-strand break repair via nonhomologous end joining 0e+00 0e+00 telomere organization 0e+00 0e+00 telomere maintenance 0e+00 0e+00 telomere maintenance via recombination

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 BASE EXCISION REPAIR 0.00e+00 0.00e+00 DNA REPAIR 0.00e+00 0.00e+00 NUCLEOTIDE EXCISION REPAIR 0.00e+00 0.00e+00 GLOBAL GENOMIC NER GG NER 0.00e+00 0.00e+00 BASE EXCISION REPAIR 0.00e+00 0.00e+00 DNA REPAIR 0.00e+00 0.00e+00 NUCLEOTIDE EXCISION REPAIR 0.00e+00 0.00e+00 GLOBAL GENOMIC NER GG NER 1.14e-11 4.38e-09 RESOLUTION OF AP SITES VIA THE MULTIPLE NUCLEOTIDE PATCH REPLACEMENT PATHWAY 4.32e-10 1.11e-07 RESOLUTION OF AP SITES VIA THE MULTIPLE NUCLEOTIDE PATCH REPLACEMENT PATHWAY 2.28e-09 7.16e-07 REPAIR SYNTHESIS FOR GAP FILLING BY DNA POL IN TC NER 2.42e-09 5.64e-07 REPAIR SYNTHESIS FOR GAP FILLING BY DNA POL IN TC NER 3.22e-09 9.88e-07 TRANSCRIPTION COUPLED NER TC NER 4.75e-09 1.07e-06 TRANSCRIPTION COUPLED NER TC NER 1.42e-08 3.06e-06 REMOVAL OF THE FLAP INTERMEDIATE FROM THE C STRAND 1.55e-08 4.42e-06 REMOVAL OF THE FLAP INTERMEDIATE FROM THE C STRAND 1.66e-08 4.72e-06 INTEGRATION OF PROVIRUS 3.73e-08 7.68e-06 EXTENSION OF TELOMERES 4.82e-08 1.29e-05 EXTENSION OF TELOMERES 6.72e-08 1.78e-05 POL SWITCHING

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 0.00e+00 0.00e+00 abnormal DNA repair 1.58e-08 3.54e-04 abnormal somatic hypermutation frequency 2.67e-08 5.16e-04 increased intestinal adenocarcinoma incidence 6.65e-08 1.03e-03 abnormal class switch recombination 9.64e-08 1.38e-03 increased skin tumor incidence 2.85e-07 3.27e-03 increased cellular sensitivity to gamma-irradiation 5.21e-07 5.46e-03 increased tumor incidence 6.59e-07 6.48e-03 abnormal mismatch repair 7.95e-07 7.36e-03 increased T cell derived lymphoma incidence 1.04e-06 9.04e-03 increased lymphoma incidence 1.88e-06 1.41e-02 increased uterus tumor incidence 3.18e-06 2.08e-02 increased intestinal adenoma incidence 8.10e-06 4.02e-02 spontaneous chromosome breakage 9.46e-06 4.55e-02 increased incidence of tumors by UV-induction 1.05e-05 4.84e-02 abnormal male meiosis 1.12e-05 5.09e-02 increased cellular sensitivity to ionizing radiation 1.32e-05 5.70e-02 increased squamous cell carcinoma incidence 1.76e-05 6.95e-02 abnormal T cell receptor V(D)J recombination 1.81e-05 7.03e-02 increased lung tumor incidence 3.46e-05 1.12e-01 decreased thymocyte number

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

²FDR corrected p-value (Benjamini-Hochberg)