Abstract

Abstract Background: System-wide profiling of genes and proteins in mammalian cells produces lists of differentially expressed genes/proteins needing to be further analyzed for their collective functions in order to extract new knowledge. Once lists of genes or proteins are generated from such experiments, they are compared to existing annotated lists created from prior knowledge organized into gene-set libraries. While many enrichment analysis tools and gene-set library databases have been developed, there is still room for improvement. Enrichr2 is a major update of the published popular tool Enrichr. Methods: Enrichr2's architecture has been redesigned to be highly scalable. The new database centric design allows Enrichr2 to perform enrichment analysis within seconds while accommodating for the rapid growth of our gene-set library database. Recent additions to our gene-set library database include: disease signatures from GEO, drug perturbations from GEO, kinase perturbations from GEO and L1000, as well as tissue protein expression from two recent publications. Principal Angle Enrichment Analysis has been implemented and is one of the available enrichment analysis scoring methods. Enrichr2 can be restricted to only consider a subspace of the genome, and it accepts input formats that are crisp or fuzzy gene sets, probe IDs from microarrays, BED files and SOFT files. Gene synonyms are also recognized and automatically converted. Users can upload their own gene-set libraries as well as access the legacy versions of our libraries. Results: Enrichr2 is an easy to use intuitive enrichment analysis web-based tool providing various visualization summaries of collective functions of gene lists. Enrichr2 includes many new gene-set libraries, alternative approaches to rank enriched terms, and various new interactive visualization approaches to display enrichment results. We applied Enrichr2 to analyze many of the gene expression datasets available at The Cancer Genome Atlas (TCGA). Global visualization of such enrichment analysis results provides a global view of the biological molecular mechanisms driving tumor behavior across cancers at the individual patient level. Conclusions: Enrichr2 is emerging as a leading search engine for annotated gene lists, taking gene set enrichment analysis to a new level. Enrichr is an open source web-based tool available online at: http://amp.pharm.mssm.edu/Enrichr Note: This abstract was not presented at the conference. Citation Format: Matthew R. Jones. Enrichr2: Next generation gene set enrichment analysis web-based tool. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-35.

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