Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool

TLDR

System‑wide profiling of genes and proteins generates lists of differentially expressed elements that must be analyzed for collective functions, yet existing enrichment tools and gene‑set libraries still have room for improvement. Enrichr is a web‑based application that can be embedded in other tools and was applied to nine cancer cell lines, comparing their enrichment signatures to matched normal tissues. Enrichr provides interactive visualizations and a new ranking approach, revealing common up‑regulation of PRC2 and H3K27me3 in many cancer cell lines and alterations in Toll‑like receptor signaling in K562 cells, and is freely available online.

Abstract

Abstract Background System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes/proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries. While many enrichment analysis tools and gene-set libraries databases have been developed, there is still room for improvement. Results Here, we present Enrichr, an integrative web-based and mobile software application that includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. We applied Enrichr to analyze nine cancer cell lines by comparing their enrichment signatures to the enrichment signatures of matched normal tissues. We observed a common pattern of up regulation of the polycomb group PRC2 and enrichment for the histone mark H3K27me3 in many cancer cell lines, as well as alterations in Toll-like receptor and interlukin signaling in K562 cells when compared with normal myeloid CD33+ cells. Such analyses provide global visualization of critical differences between normal tissues and cancer cell lines but can be applied to many other scenarios. Conclusions Enrichr is an easy to use intuitive enrichment analysis web-based tool providing various types of visualization summaries of collective functions of gene lists. Enrichr is open source and freely available online at: http://amp.pharm.mssm.edu/Enrichr .