Epigenomic annotation of genetic variants using the Roadmap Epigenome Browser

1 Investigators interact with the browser to determine the tissue specificity of the epigenetic state encompassing genetic variants in physiologically or pathogenically relevant cell types from normal or diseased samples (Supplementary Note, Supplementary Tutorial 1 and Supplementary Figs. 3 and 4). We illustrate the epigenomic annotation of two noncoding SNPs, identified from genome-wide association studies of people with multiple sclerosis10, by clustering the histone H3K4me1 profile of SNP-harboring regions and RNA-seq signal of their closest genes across multiple primary tissues and cells (Fig. 1). Both SNPs lie within putative enhancer regions. Whereas rs307896 marks an enhancer common across cell types, rs756699 is located in an enhancer specific to immune cells and is potentially targeting TCF7, a T cell–specific gene 3.8 kb downstream (Fig. 1 and Supplementary Fig. 5). Thus, reference epigenomes provide important clues into the functional To the Editor: Advances in next-generation sequencing platforms have reshaped the landscape of functional genomic and epigenomic research as well as human genetics studies. Annotation of noncoding regions in the genome with genomic and epigenomic data has facilitated the generation of new, testable hypotheses regarding the functional consequences of genetic variants associated with human complex traits1,2. Large consortia, such as the US National Institutes of Health (NIH) Roadmap Epigenomics Consortium3 and ENCODE4, have generated tens of thousands of sequencing-based genomewide data sets, creating a useful resource for the scientific community5. The WashU Epigenome Browser6–8 continues to provide a platform for investigators to effectively engage with this resource in the context of analyzing their own data. Here, we describe the Roadmap Epigenome Browser (http:// epigenomegateway.wustl.edu/browser/ roadmap/), which is based on the WashU Epigenome Browser and integrates data from both the NIH Roadmap Epigenomics Consortium and ENCODE in a visualization and bioinformatics tool that enables researchers to explore the tissue-specific regulatory roles of genetic variants in the context of disease. The browser takes advantage of the over 10,000 epigenomic data sets it currently hosts, including 346 ‘complete epigenomes’, defined as tissues and cell types for which we have collected a complete set of DNA methylation, histone modification, open chromatin and other genomic data sets9. Data from both the NIH Roadmap Epigenomics and ENCODE resources are seamlessly integrated in the browser using a new Data Hub Cluster framework (Supplementary Note and Supplementary Figs. 1 and 2). Investigators can specify any number of single nucleotide polymorphism (SNP)-associated regions and any type of epigenomic data, for which the browser automatically creates virtual data hubs through a shared hierarchical metadata annotation, retrieves the data and performs real-time clustering analysis. Epigenomic annotation of genetic variants using the Roadmap Epigenome Browser