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DREAM Module Identification Challenge – Consensus modules

PPI-STRING_Consensus_mod33

Assigned name NA Network PPI-STRING Module ID PPI-STRING_Consensus_mod33 Module size 62 genes

Module genes

This module comprises the following genes:

Gene ID Gene Symbol Gene Name 19 ABCA1 ATP binding cassette subfamily A member 1 5244 ABCB4 ATP binding cassette subfamily B member 4 149685 ADIG adipogenin 10777 ARPP21 cAMP regulated phosphoprotein 21 363026 CARM1 coactivator-associated arginine methyltransferase 1 896 CCND3 cyclin D3 10871 CD300C CD300c molecule 23097 CDK19 cyclin dependent kinase 19 1024 CDK8 cyclin dependent kinase 8 80205 CHD9 chromodomain helicase DNA binding protein 9 10370 CITED2 Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 1387 CREBBP CREB binding protein 1490 CTGF connective tissue growth factor 10655 DMRT2 doublesex and mab-3 related transcription factor 2 63950 DMRTA2 DMRT like family A2 1959 EGR2 early growth response 2 2168 FABP1 fatty acid binding protein 1 3992 FADS1 fatty acid desaturase 1 50486 G0S2 G0/G1 switch 2 57818 G6PC2 glucose-6-phosphatase catalytic subunit 2 11010 GLIPR1 GLI pathogenesis related 1 338328 GPIHBP1 glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 29841 GRHL1 grainyhead like transcription factor 1 85441 HELZ2 helicase with zinc finger 2 3156 HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase 124152 IQCK IQ motif containing K 9314 KLF4 Kruppel like factor 4 113251 LARP4 La ribonucleoprotein domain family member 4 3950 LECT2 leukocyte cell derived chemotaxin 2 3952 LEP leptin 4023 LPL lipoprotein lipase 8216 LZTR1 leucine zipper like transcription regulator 1 8930 MED1 methyl-CpG binding domain 4, DNA glycosylase 8648 NCOA1 nuclear receptor coactivator 1 10499 NCOA2 nuclear receptor coactivator 2 23054 NCOA6 nuclear receptor coactivator 6 9611 NCOR1 nuclear receptor corepressor 1 10062 NR1H3 nuclear receptor subfamily 1 group H member 3 4899 NRF1 nuclear respiratory factor 1 79991 OBFC1 STN1, CST complex subunit 5105 PCK1 phosphoenolpyruvate carboxykinase 1 8800 PEX11A peroxisomal biogenesis factor 11 alpha 123 PLIN2 perilipin 2 5465 PPARA peroxisome proliferator activated receptor alpha 5468 PPARG peroxisome proliferator activated receptor gamma 9444 QKI QKI, KH domain containing RNA binding 23518 R3HDM1 R3H domain containing 1 64333 RGL1 Rho GTPase activating protein 9 56961 SHD Src homology 2 domain containing transforming protein D 376497 SLC27A1 solute carrier family 27 member 1 6517 SLC2A4 solute carrier family 2 member 4 6604 SMARCD3 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 84690 SPATA22 spermatogenesis associated 22 252891 SRA1 steroid receptor RNA activator 1 6720 SREBF1 sterol regulatory element binding transcription factor 1 6721 SREBF2 sterol regulatory element binding transcription factor 2 6822 SULT2A1 sulfotransferase family 2A member 1 6907 TBL1X transducin beta like 1 X-linked 79718 TBL1XR1 transducin beta like 1 X-linked receptor 1 96764 TGS1 trimethylguanosine synthase 1 9325 TRIP4 thyroid hormone receptor interactor 4 23091 ZC3H13 zinc finger CCCH-type containing 13

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 3.17e-01 1.12e-53 Reactome Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) Metabolism 7.02e-02 8.77e-08 GO negative regulation of macrophage derived foam cell differentiation biological_process 6.72e-02 1.03e-20 Reactome Transcriptional regulation of white adipocyte differentiation Developmental Biology 5.04e-02 8.77e-08 GO long-chain fatty acid transport biological_process 4.59e-02 8.29e-06 GO positive regulation of triglyceride biosynthetic process biological_process 3.11e-02 8.29e-06 GO white fat cell differentiation biological_process 2.87e-02 1.03e-02 GO glucose-6-phosphatase activity molecular_function 2.75e-02 4.37e-50 GO regulation of lipid metabolic process biological_process 2.50e-02 1.35e-14 GO nuclear receptor transcription coactivator activity molecular_function 5.30e-03 1.29e-08 GO nuclear hormone receptor 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 1.03e-08 6.69e-06 monocarboxylic acid transport 1.63e-08 1.03e-05 fat cell differentiation 2.28e-08 1.42e-05 regulation of lipid storage 2.29e-08 9.87e-06 ligand-dependent nuclear receptor transcription coactivator activity 4.58e-08 2.73e-05 lipid transport 1.15e-07 6.44e-05 lipid localization 2.23e-07 1.19e-04 intracellular receptor signaling pathway 3.05e-07 1.59e-04 negative regulation of cholesterol storage 4.51e-07 2.28e-04 negative regulation of lipid storage 8.24e-07 3.98e-04 hormone-mediated signaling pathway 1.06e-06 5.01e-04 regulation of cholesterol transport 1.18e-06 5.53e-04 steroid hormone mediated signaling pathway 1.21e-06 5.65e-04 cellular response to lipid 1.27e-06 5.91e-04 regulation of lipid transport 1.65e-06 5.04e-04 transcription factor activity, transcription factor binding 1.86e-06 5.61e-04 transcription factor activity, protein binding 1.96e-06 8.82e-04 fatty acid transport 2.08e-06 9.30e-04 transcription initiation from RNA polymerase II promoter 2.45e-06 1.08e-03 carboxylic acid transport 2.50e-06 1.10e-03 cellular response to hormone stimulus

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 TRANSCRIPTIONAL REGULATION OF WHITE ADIPOCYTE DIFFERENTIATION 0.00e+00 0.00e+00 DEVELOPMENTAL BIOLOGY 0.00e+00 0.00e+00 BMAL1 CLOCK NPAS2 ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 PPARA ACTIVATES GENE EXPRESSION 0.00e+00 0.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 0.00e+00 0.00e+00 YAP1 AND WWTR1 TAZ STIMULATED GENE EXPRESSION 0.00e+00 0.00e+00 CIRCADIAN REPRESSION OF EXPRESSION BY REV ERBA 0.00e+00 0.00e+00 RORA ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 CIRCADIAN CLOCK 0.00e+00 0.00e+00 GENERIC TRANSCRIPTION PATHWAY 0.00e+00 0.00e+00 TRANSCRIPTIONAL REGULATION OF WHITE ADIPOCYTE DIFFERENTIATION 0.00e+00 0.00e+00 CIRCADIAN REPRESSION OF EXPRESSION BY REV ERBA 0.00e+00 0.00e+00 BMAL1 CLOCK NPAS2 ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 PPARA ACTIVATES GENE EXPRESSION 0.00e+00 0.00e+00 FATTY ACID TRIACYLGLYCEROL AND KETONE BODY METABOLISM 0.00e+00 0.00e+00 RORA ACTIVATES CIRCADIAN EXPRESSION 0.00e+00 0.00e+00 YAP1 AND WWTR1 TAZ STIMULATED GENE EXPRESSION 0.00e+00 0.00e+00 CIRCADIAN CLOCK 2.17e-05 3.90e-03 NOTCH1 INTRACELLULAR DOMAIN REGULATES TRANSCRIPTION 2.19e-05 3.11e-03 NOTCH1 INTRACELLULAR DOMAIN REGULATES TRANSCRIPTION

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

²FDR corrected p-value (Benjamini-Hochberg)

Mouse mutant phenotypes

P-value1 FDR2 Term 3.78e-08 6.68e-04 decreased liver triglyceride level 8.28e-06 4.10e-02 abnormal hepatobiliary system physiology 1.74e-05 6.94e-02 hepatic steatosis 4.83e-05 1.39e-01 abnormal glucose homeostasis 1.45e-04 2.90e-01 abnormal white fat cell morphology 2.20e-04 3.69e-01 abnormal muscle cell glucose uptake 2.25e-04 3.75e-01 decreased susceptibility to hepatic steatosis 2.26e-04 3.76e-01 increased circulating ketone body level 2.34e-04 3.85e-01 decreased gonadal fat pad weight 2.87e-04 4.38e-01 abnormal white adipose tissue physiology 3.88e-04 5.23e-01 increased circulating free fatty acid level 3.96e-04 5.28e-01 decreased white fat cell size 5.92e-04 6.71e-01 decreased activity of thyroid 6.92e-04 7.31e-01 abnormal pulmonary alveolus morphology 7.32e-04 7.56e-01 abnormal triglyceride level 9.38e-04 8.69e-01 abnormal lipid homeostasis 9.59e-04 8.83e-01 increased circulating triglyceride level 9.98e-04 9.02e-01 increased liver cholesterol level 1.23e-03 1.00e+00 abnormal lipid level 1.34e-03 1.00e+00 increased insulin sensitivity

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

²FDR corrected p-value (Benjamini-Hochberg)