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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod181

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod181 Module size 55 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 100526739 APITD1-CORT CENPS-CORT readthrough 79915 ATAD5 ATPase family, AAA domain containing 5 641 BLM BLM RecQ like helicase 100507650 C14orf164 ring finger protein 212B 644041 C18orf63 chromosome 18 open reading frame 63 23586 DDX58 DExD/H-box helicase 58 79132 DHX58 DExH-box helicase 58 23405 DICER1 dicer 1, ribonuclease III 283987 DMC1 HID1 domain containing 1763 DNA2 DNA replication helicase/nuclease 2 146956 EME1 essential meiotic structure-specific endonuclease 1 197342 EME2 essential meiotic structure-specific endonuclease subunit 2 2073 ERCC5 ERCC excision repair 5, endonuclease 112479 ERI2 ERI1 exoribonuclease family member 2 9156 EXO1 exonuclease 1 57697 FANCM FA complementation group M 84893 FBXO18 F-box DNA helicase 1 2237 FEN1 flap structure-specific endonuclease 1 348654 GEN1 GEN1, Holliday junction 5' flap endonuclease 92797 HELB DNA helicase B 64135 IFIH1 interferon induced with helicase C domain 1 4361 MRE11A MRE11 homolog, double strand break repair nuclease 80198 MUS81 MUS81 structure-specific endonuclease subunit 10401 PIAS3 protein inhibitor of activated STAT 3 367645 PIF1 PIF1 5'-to-3' DNA helicase 56852 RAD18 RAD18, E3 ubiquitin protein ligase 10111 RAD50 RAD50 double strand break repair protein 5888 RAD51 RAD51 recombinase 729475 RAD51AP2 RAD51 associated protein 2 5890 RAD51B RAD51 paralog B 5889 RAD51C RAD51 paralog C 5892 RAD51D RAD51 paralog D 5893 RAD52 RAD52 homolog, DNA repair protein 5965 RECQL RecQ like helicase 9400 RECQL5 RecQ like helicase 5 119392 SFR1 SWI5 dependent homologous recombination repair protein 1 548593 SLX1A SLX1 homolog A, structure-specific endonuclease subunit 79008 SLX1B SLX1 homolog B, structure-specific endonuclease subunit 23626 SPO11 SPO11, initiator of meiotic double stranded breaks 375757 SWI5 SWI5 homologous recombination repair protein 81550 TDRD3 tudor domain containing 3 387521 TMEM189 transmembrane protein 189 387522 TMEM189-UBE2V1 TMEM189-UBE2V1 readthrough 7150 TOP1 DNA topoisomerase I 116447 TOP1MT DNA topoisomerase I mitochondrial 8940 TOP3B DNA topoisomerase III beta 7158 TP53BP1 tumor protein p53 binding protein 1 26140 TTLL3 tubulin tyrosine ligase like 3 164395 TTLL9 tubulin tyrosine ligase like 9 7486 WRN Werner syndrome RecQ like helicase 56897 WRNIP1 Werner helicase interacting protein 1 7516 XRCC2 X-ray repair cross complementing 2 7517 XRCC3 X-ray repair cross complementing 3 57178 ZMIZ1 zinc finger MIZ-type containing 1 83637 ZMIZ2 zinc finger MIZ-type 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 4.16e-01 7.67e-08 GO DNA topoisomerase type I activity molecular_function 3.18e-01 2.46e-10 GO four-way junction helicase activity molecular_function 2.83e-01 2.58e-17 GO crossover junction endodeoxyribonuclease activity molecular_function 2.04e-01 2.58e-12 GO 5'-flap endonuclease activity molecular_function 1.79e-01 2.91e-21 GO replication fork cellular_component 1.11e-01 1.60e-08 GO single-stranded DNA-dependent ATPase activity molecular_function 1.03e-01 3.23e-34 Reactome Resolution of D-loop Structures through Holliday Junction Intermediates DNA Repair 7.69e-02 1.59e-06 GO mitotic recombination biological_process 7.33e-02 1.06e-17 GO four-way junction DNA binding molecular_function 5.91e-02 6.26e-34 Reactome Resolution of D-Loop Structures DNA Repair 3.01e-02 1.80e-12 GO reciprocal meiotic recombination biological_process 3.01e-02 4.83e-08 GO exonuclease activity molecular_function 2.29e-02 2.51e-12 GO helicase activity molecular_function 2.24e-02 7.27e-21 GO DNA recombination biological_process 1.53e-02 1.07e-16 GO nucleic acid phosphodiester bond hydrolysis biological_process 1.24e-02 1.15e-28 GO double-strand break repair via homologous recombination biological_process 7.09e-03 4.75e-04 Reactome NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 Immune System 7.08e-03 4.75e-04 GO positive regulation of tumor necrosis factor secretion biological_process 7.08e-03 4.75e-04 GO positive regulation of interferon-alpha production biological_process 1.32e-03 8.16e-13 GO replication fork processing 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 0e+00 0e+00 DNA conformation change 0e+00 0e+00 DNA metabolic process 0e+00 0e+00 DNA repair 0e+00 0e+00 reciprocal meiotic recombination 0e+00 0e+00 strand displacement 0e+00 0e+00 DNA synthesis involved in DNA repair 0e+00 0e+00 DNA recombinase assembly 0e+00 0e+00 meiotic cell cycle 0e+00 0e+00 DNA biosynthetic process 0e+00 0e+00 telomere organization 0e+00 0e+00 response to ionizing radiation 0e+00 0e+00 cellular response to DNA damage stimulus 0e+00 0e+00 strand invasion 0e+00 0e+00 DNA geometric change 0e+00 0e+00 DNA replication 0e+00 0e+00 DNA-dependent DNA replication 0e+00 0e+00 double-strand break repair 0e+00 0e+00 DNA duplex unwinding 0e+00 0e+00 replication fork processing 0e+00 0e+00 recombinational repair

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

²FDR corrected p-value (Benjamini-Hochberg)

Reactome

P-value1 FDR2 Term 6.82e-10 2.28e-07 DNA REPAIR 3.72e-09 8.52e-07 DNA REPAIR 4.81e-09 1.08e-06 HOMOLOGOUS RECOMBINATION REPAIR OF REPLICATION INDEPENDENT DOUBLE STRAND BREAKS 1.40e-08 4.02e-06 HOMOLOGOUS RECOMBINATION REPAIR OF REPLICATION INDEPENDENT DOUBLE STRAND BREAKS 3.52e-08 7.27e-06 MEIOTIC RECOMBINATION 5.06e-08 1.02e-05 DOUBLE STRAND BREAK REPAIR 1.01e-07 2.60e-05 DOUBLE STRAND BREAK REPAIR 2.85e-07 5.31e-05 MEIOSIS 7.69e-07 1.76e-04 MEIOTIC RECOMBINATION 2.08e-06 4.43e-04 MEIOSIS 2.86e-04 3.93e-02 REMOVAL OF THE FLAP INTERMEDIATE FROM THE C STRAND 4.72e-04 6.12e-02 PROCESSIVE SYNTHESIS ON THE LAGGING STRAND 6.04e-04 6.41e-02 REMOVAL OF THE FLAP INTERMEDIATE FROM THE C STRAND 6.80e-04 8.40e-02 NFKB ACTIVATION THROUGH FADD RIP1 PATHWAY MEDIATED BY CASPASE 8 AND10 7.01e-04 8.60e-02 LAGGING STRAND SYNTHESIS 1.18e-03 1.16e-01 PROCESSIVE SYNTHESIS ON THE LAGGING STRAND 1.39e-03 1.56e-01 EXTENSION OF TELOMERES 1.59e-03 1.52e-01 NFKB ACTIVATION THROUGH FADD RIP1 PATHWAY MEDIATED BY CASPASE 8 AND10 1.70e-03 1.61e-01 TRAF3 DEPENDENT IRF ACTIVATION PATHWAY 1.93e-03 1.80e-01 LAGGING STRAND SYNTHESIS

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 1.86e-09 5.70e-05 chromosomal instability 8.01e-08 1.18e-03 abnormal DNA repair 8.29e-07 7.48e-03 increased lymphoma incidence 1.08e-06 9.19e-03 aneuploidy 6.33e-06 3.39e-02 induced chromosome breakage 4.75e-05 1.38e-01 increased cellular sensitivity to gamma-irradiation 8.82e-05 2.09e-01 increased tumor incidence 1.77e-04 3.24e-01 abnormal female meiosis 2.03e-04 3.52e-01 elevated level of mitotic sister chromatid exchange 2.97e-04 4.46e-01 abnormal male meiosis 3.00e-04 4.47e-01 spontaneous chromosome breakage 3.41e-04 4.85e-01 decreased cell proliferation 3.83e-04 5.20e-01 abnormal cell physiology 3.95e-04 5.28e-01 chromosome breakage 6.16e-04 6.83e-01 abnormal telomere morphology 6.46e-04 7.03e-01 increased mortality induced by gamma-irradiation 7.87e-04 7.83e-01 abnormal seminiferous tubule morphology 9.72e-04 8.91e-01 female infertility 1.03e-03 9.16e-01 increased susceptibility to viral infection 1.17e-03 9.85e-01 abnormal reproductive system morphology

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

²FDR corrected p-value (Benjamini-Hochberg)