MSigDB v3.1 Release Notes
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Improved mapping to common gene identifiers
MSigDB now uses human Entrez Gene IDs as the common gene identifiers for all gene sets. Gene sets come from a number of different sources and are originally specified using a variety of gene identifiers. The MSigDB gene sets are converted to a common set of gene identifiers so they can be used in GSEA and other tools. Previous releases of MSigDB used human gene symbols for this purpose. Researchers prefer working with gene symbols because they can easily recognize, remember and put them in the context of their work. Unfortunately, a gene usually has multiple different symbols. Conversely, the same symbol may refer to a number of different genes. Finally, gene symbols change frequently. To overcome these issues, we now use Entrez Gene IDs as the universal gene identifier for all MSigDB gene sets. Entrez Gene IDs identify genes uniquely and never change. For convenience, we continue to display gene sets as human gene symbols by default. However, the symbols are now unambiguously derived from the corresponding human Entrez Gene IDs. For non-human original members, we first convert them to the organism-specific Entrez Gene IDs and then seek their orthologous counterparts as human Entrez Gene IDs. Finally, we derive human gene symbols from the corresponding common gene identifiers for all standard uses. Note that all gene sets are also available as the original identifiers specified by the source and as Entrez Gene IDs.
Human Entrez Gene IDs and the corresponding symbols for the MSigDB v3.1 gene sets are based on gene_info.gz and gene_history.gz, downloaded from the Entrez Gene FTP site on November, 15, 2011. Mouse -> Human and Rat -> Human 1:1 orthologous relationships are from Mouse Genome Informatics (MGI).MSigDB gene sets are subject to size and similarity restrictions. After mapping to human Entrez Gene IDs, filters were applied to exclude sets with:
- - fewer than 5 genes (C2:CGP only)
- - fewer than 10 (all other collections)
- - more than 2,000 genes
- - 90% or higher similarity (overlap) to other set(s) within a collection
New collection C6: Oncogenic Pathway Activation Modules
C6: Oncogenic Pathway Activation Modules is a new collection of 189 gene sets. These gene sets represent expression signatures derived directly from microarray data from experiments involving gain or loss of function of several established cancer genes in well defined, "clean" experimental systems. In this context, gain of function stands for increased activity of a cancer gene by means of over-expression or treatment with a chemical modulator. Conversely, loss of function stands for diminished activity of the cancer gene by means of RNAi knockdown, gene knockout, or enzymatic inhibition.
New gene sets curated from papers1,035 new gene sets curated from papers were added to the C2:CGP (Chemical and Genetic Perturbations) sub-collection. In a review of the whole collection, 12 existing sets were renamed and 29 sets were deprecated. Renamed and deprecated sets are listed here.
New canonical pathway gene sets
The CP (Canonical Pathways) sub-collection has two new sources of gene sets. (1) 132 gene sets were collected from the Munich Information Center for Protein Sequences (MIPS) CORUM database, which provides a resource of manually annotated protein complexes from mammalian organisms. The gene sets correspond to human protein complexes extracted from the CORUM database released on February 17, 2012. (2) 196 gene sets were collected from the Pathway Interaction Database (PID), which is a highly-structured, curated collection of information about known biomolecular interactions and key cellular processes assembled into signaling pathways. This was a collaborative project between the NCI and Nature Publishing Group (NPG) from 2006 until September 22nd, 2012, and is no longer being updated. In collaboration with the PID resource we extracted the gene sets from the PID data file (uniprot.tab) downloaded on May 15, 2012.
The sets in the CP (Canonical Pathways): the entire Reactome sub-collection was updated to version 44 of Reactome. Reactome is a curated knowledgebase of biological pathways in humans. This update created 399 new sets, leaving 275 sets from v3.0 MSigDB unchanged and 155 deprecated. No sets were renamed. Deprecated sets are listed here.
Updates to C4: Cancer Modules
The gene sets in C4: Cancer Modules represent clusters of transcriptionally co-regulated genes that both share a common functional annotation and have been found significantly deregulated in tumors. They correspond to the modules described in Segal et al., 2004. For the MSigDB v3.1 release, these gene sets were re-mapped to gene symbols from the Entrez Gene IDs as they appeared in original source files prior to v2.5. 23 sets were deprecated because they contained fewer than 10 genes. Names of all other sets were changed to upper case font to match the naming convention throughout MSigDB. Renamed and deprecated sets are listed here.