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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod183

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod183 Module size 32 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 672 BRCA1 BRCA1, DNA repair associated 595 CCND1 cyclin D1 898 CCNE1 cyclin E1 9134 CCNE2 cyclin E2 993 CDC25A cell division cycle 25A 1026 CDKN1A cyclin dependent kinase inhibitor 1A 1027 CDKN1B cyclin dependent kinase inhibitor 1B 1028 CDKN1C cyclin dependent kinase inhibitor 1C 8804 CREG1 cellular repressor of E1A stimulated genes 1 1869 E2F1 E2F transcription factor 1 1870 E2F2 E2F transcription factor 2 1871 E2F3 E2F transcription factor 3 1874 E2F4 E2F transcription factor 4 1875 E2F5 E2F transcription factor 5 144455 E2F7 E2F transcription factor 7 23151 GRAMD4 GRAM domain containing 4 84456 L3MBTL3 L3MBTL3, histone methyl-lysine binding protein 55957 LIN37 lin-37 DREAM MuvB core complex component 91750 LIN52 lin-52 DREAM MuvB core complex component 132660 LIN54 lin-54 DREAM MuvB core complex component 286826 LIN9 lin-9 DREAM MuvB core complex component 5542 PRB1 proline rich protein BstNI subfamily 1 653247 PRB2 proline rich protein BstNI subfamily 2 5925 RB1 RB transcriptional corepressor 1 5933 RBL1 RB transcriptional corepressor like 1 5934 RBL2 RB transcriptional corepressor like 2 9792 SERTAD2 SERTA domain containing 2 6689 SPIB Spi-B transcription factor 7027 TFDP1 transcription factor Dp-1 7029 TFDP2 transcription factor Dp-2 51270 TFDP3 transcription factor Dp family member 3 10155 TRIM28 tripartite motif containing 28

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 4.50e-01 1.14e-31 Reactome Transcription of E2F targets under negative control by DREAM complex Cell Cycle 2.90e-01 1.92e-08 Reactome Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes Cell Cycle 1.22e-01 4.96e-14 Reactome TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest Gene expression (Transcription) 6.47e-02 7.34e-30 Reactome Cyclin D associated events in G1 Cell Cycle 6.41e-02 7.34e-30 Reactome G1 Phase Cell Cycle 4.15e-02 2.89e-34 Reactome G0 and Early G1 Cell Cycle 3.74e-02 7.65e-18 Reactome Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 Cell Cycle 2.62e-02 9.58e-08 Reactome PTK6 Regulates Cell Cycle Signal Transduction 9.73e-03 1.88e-09 GO proximal promoter sequence-specific DNA binding molecular_function 8.74e-03 2.12e-15 GO RNA polymerase II transcription factor complex cellular_component 1.11e-03 1.05e-06 GO cyclin-dependent protein serine/threonine kinase inhibitor activity molecular_function 7.29e-04 3.31e-21 GO regulation of cell cycle 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 cell cycle checkpoint 0.00e+00 0.00e+00 cell cycle G1/S phase transition 0.00e+00 0.00e+00 negative regulation of G1/S transition of mitotic cell cycle 0.00e+00 0.00e+00 negative regulation of cell cycle G1/S phase transition 0.00e+00 0.00e+00 G1/S transition of mitotic cell cycle 0.00e+00 0.00e+00 transcription factor complex 1.64e-11 1.46e-08 mitotic cell cycle phase transition 1.99e-11 1.77e-08 cell cycle phase transition 3.65e-11 3.16e-08 regulation of cell cycle arrest 4.13e-11 3.56e-08 mitotic G1 DNA damage checkpoint 4.13e-11 3.56e-08 mitotic G1/S transition checkpoint 4.14e-11 3.57e-08 DNA damage checkpoint 4.17e-11 3.59e-08 G1 DNA damage checkpoint 6.84e-11 5.78e-08 signal transduction by p53 class mediator 1.38e-10 8.29e-08 cyclin-dependent protein serine/threonine kinase regulator activity 1.40e-10 1.14e-07 mitotic cell cycle checkpoint 2.06e-10 1.66e-07 DNA damage response, signal transduction by p53 class mediator 2.12e-10 1.70e-07 mitotic DNA damage checkpoint 2.13e-10 1.71e-07 regulation of G1/S transition of mitotic cell cycle 2.81e-10 2.23e-07 positive regulation of cell cycle arrest

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 CELL CYCLE 0.00e+00 0.00e+00 MITOTIC G1 G1 S PHASES 0.00e+00 0.00e+00 G1 PHASE 0.00e+00 0.00e+00 CELL CYCLE MITOTIC 0.00e+00 0.00e+00 G0 AND EARLY G1 0.00e+00 0.00e+00 MITOTIC G1 G1 S PHASES 0.00e+00 0.00e+00 G1 PHASE 0.00e+00 0.00e+00 G0 AND EARLY G1 3.20e-06 5.15e-04 G1 S TRANSITION 1.02e-05 1.52e-03 E2F MEDIATED REGULATION OF DNA REPLICATION 1.49e-05 2.17e-03 G1 S SPECIFIC TRANSCRIPTION 2.10e-05 2.99e-03 CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION 2.45e-05 3.45e-03 SMAD2 SMAD3 SMAD4 HETEROTRIMER REGULATES TRANSCRIPTION 2.99e-05 4.14e-03 PRE NOTCH TRANSCRIPTION AND TRANSLATION 3.88e-05 5.30e-03 S PHASE 4.75e-05 7.96e-03 PRE NOTCH TRANSCRIPTION AND TRANSLATION 5.06e-05 8.44e-03 G1 S SPECIFIC TRANSCRIPTION 8.02e-05 1.27e-02 E2F MEDIATED REGULATION OF DNA REPLICATION 8.19e-05 1.06e-02 TRANSCRIPTIONAL ACTIVITY OF SMAD2 SMAD3 SMAD4 HETEROTRIMER 9.54e-05 1.49e-02 SMAD2 SMAD3 SMAD4 HETEROTRIMER REGULATES TRANSCRIPTION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 5.72e-06 3.17e-02 abnormal cell cycle 1.14e-05 5.13e-02 increased cell proliferation 1.04e-04 2.32e-01 increased incidence of tumors by ionizing radiation induction 3.12e-04 4.60e-01 abnormal definitive hematopoiesis 3.23e-04 4.71e-01 abnormal cell proliferation 3.90e-04 5.24e-01 increased fibroblast proliferation 4.04e-04 5.35e-01 mammary gland duct hyperplasia 4.77e-04 5.92e-01 abnormal prostate gland dorsolateral lobe morphology 4.96e-04 6.03e-01 increased pituitary gland tumor incidence 6.97e-04 7.33e-01 increased parametrial fat pad weight 7.46e-04 7.62e-01 increased neuronal precursor cell number 7.59e-04 7.66e-01 abnormal cell cycle checkpoint function 9.35e-04 8.68e-01 increased metastatic potential 1.14e-03 9.71e-01 abnormal cell death 1.55e-03 1.00e+00 mammary gland hyperplasia 1.63e-03 1.00e+00 increased cellular sensitivity to gamma-irradiation 1.67e-03 1.00e+00 abnormal chromosome number 1.69e-03 1.00e+00 abnormal awl hair morphology 2.00e-03 1.00e+00 abnormal erythropoiesis 2.07e-03 1.00e+00 decreased small intestinal villus size

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

²FDR corrected p-value (Benjamini-Hochberg)