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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod297

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod297 Module size 40 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 196 AHR aryl hydrocarbon receptor 1543 AHRR cytochrome P450 family 1 subfamily A member 1 405 ARNT aryl hydrocarbon receptor nuclear translocator 406 ARNTL aryl hydrocarbon receptor nuclear translocator like 56938 ARNTL2 aryl hydrocarbon receptor nuclear translocator like 2 444 ASPH aspartate beta-hydroxylase 8553 BHLHE40 basic helix-loop-helix family member e40 79365 BHLHE41 basic helix-loop-helix family member e41 29547 CALCOCO1 homer scaffold protein 2 150383 CDPF1 cysteine rich DPF motif domain containing 1 1053 CEBPE CCAAT enhancer binding protein epsilon 1054 CEBPG CCAAT enhancer binding protein gamma 9575 CLOCK clock circadian regulator 58487 CREBZF CREB/ATF bZIP transcription factor 1407 CRY1 cryptochrome circadian regulator 1 1408 CRY2 cryptochrome circadian regulator 2 2638 DBP GC, vitamin D binding protein 1649 DDIT3 DNA damage inducible transcript 3 50514 DEC1 deleted in esophageal cancer 1 54583 EGLN1 egl-9 family hypoxia inducible factor 1 112398 EGLN2 egl-9 family hypoxia inducible factor 2 112399 EGLN3 egl-9 family hypoxia inducible factor 3 2034 EPAS1 endothelial PAS domain protein 1 201163 FLCN folliculin 3091 HIF1A hypoxia inducible factor 1 subunit alpha 64344 HIF3A hypoxia inducible factor 3 subunit alpha 2034 HLF endothelial PAS domain protein 1 85457 KIAA1737 CLOCK interacting pacemaker 337963 KRTAP23-1 keratin associated protein 23-1 4780 NFE2L2 nuclear factor, erythroid 2 like 2 4783 NFIL3 nuclear factor, interleukin 3 regulated 4862 NPAS2 neuronal PAS domain protein 2 5187 PER1 period circadian regulator 1 8864 PER2 period circadian regulator 2 8863 PER3 period circadian regulator 3 6478 SIAH2 siah E3 ubiquitin protein ligase 2 121599 SPIC Spi-C transcription factor 548313 SSX4B SSX family member 4B 7008 TEF TEF, PAR bZIP transcription factor 24874 VHL von Hippel-Lindau tumor suppressor

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 1.82e-01 1.62e-13 Reactome BMAL1:CLOCK,NPAS2 activates circadian gene expression Circadian Clock 1.77e-01 2.94e-07 Reactome Aryl hydrocarbon receptor signalling Metabolism 1.75e-01 1.28e-05 Reactome Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha Cellular responses to external stimuli 1.29e-01 2.94e-07 GO peptidyl-proline 4-dioxygenase activity molecular_function 1.05e-01 3.48e-16 GO regulation of transcription from RNA polymerase II promoter in response to hypoxia biological_process 9.02e-02 2.90e-12 GO entrainment of circadian clock by photoperiod biological_process 7.89e-02 4.70e-07 GO peptidyl-proline hydroxylation to 4-hydroxy-L-proline biological_process 5.91e-02 1.00e-06 GO negative regulation of circadian rhythm biological_process 5.79e-02 3.38e-09 Reactome Regulation of gene expression by Hypoxia-inducible Factor Cellular responses to external stimuli 5.55e-02 3.40e-16 GO E-box binding molecular_function 4.23e-02 1.00e-06 GO response to redox state biological_process 3.68e-02 7.07e-20 GO circadian regulation of gene expression biological_process 3.57e-02 1.88e-19 Reactome Circadian Clock Circadian Clock 2.80e-02 1.84e-06 GO transcription factor activity, transcription factor binding molecular_function 2.73e-02 9.48e-08 GO response to light stimulus biological_process 1.79e-02 4.25e-05 Reactome PTK6 Expression Signal Transduction 1.17e-02 2.38e-06 GO transcription corepressor binding molecular_function 9.13e-03 2.78e-04 GO PERK-mediated unfolded protein response biological_process 5.49e-03 9.48e-08 GO sequence-specific double-stranded DNA binding molecular_function 3.12e-03 4.35e-14 GO circadian rhythm biological_process 6.50e-06 6.75e-06 GO transcription factor activity, RNA polymerase II proximal promoter sequence-specific DNA 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 0.00e+00 0.00e+00 circadian regulation of gene expression 0.00e+00 0.00e+00 rhythmic process 0.00e+00 0.00e+00 circadian rhythm 0.00e+00 0.00e+00 regulation of DNA-templated transcription in response to stress 0.00e+00 0.00e+00 regulation of transcription from RNA polymerase II promoter in response to stress 9.17e-11 7.64e-08 transcription from RNA polymerase II promoter 1.03e-10 8.53e-08 negative regulation of glucocorticoid receptor signaling pathway 1.04e-10 6.33e-08 transcription regulatory region DNA binding 1.05e-10 6.38e-08 regulatory region DNA binding 1.26e-10 1.03e-07 regulation of transcription from RNA polymerase II promoter in response to hypoxia 2.45e-09 1.74e-06 regulation of circadian rhythm 3.42e-09 1.67e-06 E-box binding 6.49e-09 2.64e-06 transcription factor complex 2.41e-08 1.49e-05 photoperiodism 2.44e-08 1.51e-05 cellular response to hypoxia 2.49e-08 1.07e-05 RNA polymerase II transcription factor activity, sequence-specific DNA binding 2.79e-08 1.71e-05 entrainment of circadian clock 3.83e-08 2.30e-05 cellular response to decreased oxygen levels 6.06e-08 3.54e-05 protein hydroxylation 6.82e-08 3.96e-05 cellular response to oxygen levels

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 BMAL1 CLOCK NPAS2 ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 CIRCADIAN CLOCK 0.00e+00 0.00e+00 REGULATION OF HYPOXIA INDUCIBLE FACTOR HIF BY OXYGEN 0.00e+00 0.00e+00 OXYGEN DEPENDENT PROLINE HYDROXYLATION OF HYPOXIA INDUCIBLE FACTOR ALPHA 0.00e+00 0.00e+00 BMAL1 CLOCK NPAS2 ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 CIRCADIAN CLOCK 0.00e+00 0.00e+00 REGULATION OF HYPOXIA INDUCIBLE FACTOR HIF BY OXYGEN 0.00e+00 0.00e+00 OXYGEN DEPENDENT PROLINE HYDROXYLATION OF HYPOXIA INDUCIBLE FACTOR ALPHA 5.84e-06 9.09e-04 CIRCADIAN REPRESSION OF EXPRESSION BY REV ERBA 1.14e-05 1.68e-03 RORA ACTIVATES CIRCADIAN EXPRESSION 2.48e-05 4.40e-03 CIRCADIAN REPRESSION OF EXPRESSION BY REV ERBA 3.47e-05 6.01e-03 RORA ACTIVATES CIRCADIAN EXPRESSION 4.05e-03 3.43e-01 PPARA ACTIVATES GENE EXPRESSION 5.71e-03 5.10e-01 PPARA ACTIVATES GENE EXPRESSION 2.74e-02 1.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 3.48e-02 1.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 3.56e-02 1.00e+00 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 3.56e-02 1.00e+00 ACTIVATION OF CHAPERONES BY ATF6 ALPHA 4.21e-02 1.00e+00 ACTIVATION OF CHAPERONE GENES BY ATF6 ALPHA 4.62e-02 1.00e+00 ACTIVATION OF CHAPERONES BY ATF6 ALPHA

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 2.15e-08 4.35e-04 shortened circadian period 3.39e-08 6.20e-04 decreased circulating noradrenaline level 1.74e-07 2.21e-03 arrhythmic circadian persistence 2.10e-07 2.59e-03 abnormal sleep pattern 5.97e-06 3.24e-02 prolonged circadian period 1.40e-05 5.86e-02 decreased circulating adrenaline level 5.58e-05 1.54e-01 abnormal response to injury 5.60e-05 1.54e-01 abnormal circadian phase 5.93e-05 1.60e-01 increased spleen weight 8.82e-05 2.09e-01 abnormal basal metabolism 1.36e-04 2.79e-01 patent ductus venosus 1.40e-04 2.84e-01 abnormal pregnancy 3.31e-04 4.74e-01 hepatic steatosis 4.89e-04 5.99e-01 increased hemoglobin content 7.07e-04 7.40e-01 abnormal circadian regulation of heart rate 7.09e-04 7.41e-01 advanced circadian phase 7.71e-04 7.74e-01 abnormal circadian regulation of systemic arterial blood pressure 8.77e-04 8.35e-01 delayed circadian phase 9.11e-04 8.53e-01 abnormal heart right ventricle pressure 9.52e-04 8.78e-01 increased incidence of tumors by chemical induction

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

²FDR corrected p-value (Benjamini-Hochberg)