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The Molecular Signatures Database Hallmark Gene Set Collection
Open accessAbstract
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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“Performing gene set enrichment analysis using the MSigDB Hallmark gene sets (Liberzon et al. 2015), we observed that Myc target genes and DNA repair pathways were up-regulated, whereas TRP53 pathway genes were down-regulated (Fig. 4D).”
From Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging (2019) · cites this paper as Liberzon et al. 2015
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“Gene set enrichment analyses were performed according to standard procedures [39, 40] on two published RNA-seq datasets [31, 48]”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [40]
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“( F ) Hallmark gene set (81) enrichment plot for genes upregulated in control reactive astrocytes as compared to Ts21 reactive astrocytes (DEGs: adj. p<0.01, Wilcoxon Rank Sum test).”
From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [81]
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“Moreover, carriers of MNAT1 gene, which is one of the leading genes in the G2/M checkpoint pathway58, were linked to better treatment outcome of FOLFOX54.”
From Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer (2025) · cites this paper as [58]
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“Significant enrichment of hallmark gene sets (33) for inflammatory response and NF-κB signaling were found in the MDP-l,d dataset (Table S8).”
From Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy (2021) · cites this paper as [33]
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Metadata
- Authors
- Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Mesirov, Jill P.
- Tamayo, Pablo
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 1
- Issue
- 6
- Pages
- 417-425
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC4707969
- OpenAlex
- W2214074259
- Cited by
- 13,807
- References
- 37
- Citations by year
- 2026: 2174 · 2025: 2294 · 2024: 2415 · 2023: 1982 · 2022: 1708 · 2021: 1298 · 2020: 926 · 2019: 534 · 2018: 270 · 2017: 154 · 2016: 44
- FWCI
- 68.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA154480, U54CA112962, R01CA121941)
- National Institute of General Medical Sciences (R01GM074024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Health Informatics › Biomedical Text Mining and Ontologies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- Hallmark gene sets, gene set enrichment analysis, biological processes, cancer hallmarks
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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