The Molecular Signatures Database (MSigDB) Hallmark Gene Set Collection

Overview

Journal Cell Syst

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Jan 16

PMID 26771021

Citations 6010

Authors

Arthur Liberzon

Chet Birger

Helga Thorvaldsdottir

Mahmoud Ghandi

Jill P Mesirov

Pablo Tamayo

Affiliations

Soon will be listed here.

Abstract

The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

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References

Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov J . GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007; 23(23):3251-3. DOI: 10.1093/bioinformatics/btm369. View

Ferbeyre G, Moriggl R . The role of Stat5 transcription factors as tumor suppressors or oncogenes. Biochim Biophys Acta. 2010; 1815(1):104-14. DOI: 10.1016/j.bbcan.2010.10.004. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Akhurst R, Hata A . Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov. 2012; 11(10):790-811. PMC: 3520610. DOI: 10.1038/nrd3810. View

Cho Y, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H . Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2010; 29(11):1424-30. PMC: 3082983. DOI: 10.1200/JCO.2010.28.5148. View

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

Brunet J, Tamayo P, Golub T, Mesirov J . Metagenes and molecular pattern discovery using matrix factorization. Proc Natl Acad Sci U S A. 2004; 101(12):4164-9. PMC: 384712. DOI: 10.1073/pnas.0308531101. View

Stark G, Darnell Jr J . The JAK-STAT pathway at twenty. Immunity. 2012; 36(4):503-14. PMC: 3909993. DOI: 10.1016/j.immuni.2012.03.013. View

Good P . Analyzing the large number of variables in biomedical imagery: a brief review. J Biopharm Stat. 2011; 21(6):1094-9. DOI: 10.1080/10543406.2011.607772. View

10.

Huang D, Sherman B, Lempicki R . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2008; 37(1):1-13. PMC: 2615629. DOI: 10.1093/nar/gkn923. View

11.

Barbie D, Tamayo P, Boehm J, Kim S, Moody S, Dunn I . Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009; 462(7269):108-12. PMC: 2783335. DOI: 10.1038/nature08460. View

12.

Mootha V, Lindgren C, Eriksson K, Subramanian A, Sihag S, Lehar J . PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003; 34(3):267-73. DOI: 10.1038/ng1180. View

13.

Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov J . Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011; 27(12):1739-40. PMC: 3106198. DOI: 10.1093/bioinformatics/btr260. View

14.

Matsumoto T, Sakari M, Okada M, Yokoyama A, Takahashi S, Kouzmenko A . The androgen receptor in health and disease. Annu Rev Physiol. 2012; 75:201-24. DOI: 10.1146/annurev-physiol-030212-183656. View

15.

Northcott P, Jones D, Kool M, Robinson G, Gilbertson R, Cho Y . Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012; 12(12):818-34. PMC: 3889646. DOI: 10.1038/nrc3410. View

16.

Barrett T, Troup D, Wilhite S, Ledoux P, Rudnev D, Evangelista C . NCBI GEO: mining tens of millions of expression profiles--database and tools update. Nucleic Acids Res. 2006; 35(Database issue):D760-5. PMC: 1669752. DOI: 10.1093/nar/gkl887. View

17.

Zeisberg M, Neilson E . Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 2009; 119(6):1429-37. PMC: 2689132. DOI: 10.1172/JCI36183. View

18.

Folkman J, DAmore P . Blood vessel formation: what is its molecular basis?. Cell. 1996; 87(7):1153-5. DOI: 10.1016/s0092-8674(00)81810-3. View

19.

Rustici G, Kolesnikov N, Brandizi M, Burdett T, Dylag M, Emam I . ArrayExpress update--trends in database growth and links to data analysis tools. Nucleic Acids Res. 2012; 41(Database issue):D987-90. PMC: 3531147. DOI: 10.1093/nar/gks1174. View

20.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A, Kim S . The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7. PMC: 3320027. DOI: 10.1038/nature11003. View