Integrative analysis of 111 reference human epigenomes¶
Why this mattered¶
TBD
Abstract¶
The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
Related¶
- cite → Topological domains in mammalian genomes identified by analysis of chromatin interactions — The Roadmap Epigenomics analysis relates chromatin states to three-dimensional genome organization using topological domains identified by Hi-C chromatin interaction maps.
- cite → Gene Ontology: tool for the unification of biology — The Roadmap Epigenomics analysis uses Gene Ontology categories to interpret biological functions enriched among genes linked to epigenomic annotations.
- cite → Fast and accurate short read alignment with Burrows–Wheeler transform — The Roadmap Epigenomics pipelines use BWA-style Burrows-Wheeler short-read alignment to map sequencing reads from epigenomic assays to the human genome.
- cite → Mapping and quantifying mammalian transcriptomes by RNA-Seq — The Roadmap Epigenomics analysis uses RNA-seq transcript quantification concepts from mammalian transcriptome mapping to connect epigenomic states with gene expression.
- cite → An integrated encyclopedia of DNA elements in the human genome — Roadmap Epigenomics extends ENCODE's functional DNA element catalog by profiling comparable epigenomic marks across many primary human tissues and cell types.
- enables → The GTEx Consortium atlas of genetic regulatory effects across human tissues — The Roadmap Epigenomics reference maps enabled GTEx to interpret tissue-specific eQTLs through chromatin states and regulatory annotations.
- cite ← The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans — The GTEx pilot links expression quantitative trait loci to regulatory annotations from reference human epigenomes.
- cite ← The GTEx Consortium atlas of genetic regulatory effects across human tissues — The GTEx atlas links eQTLs to the Roadmap Epigenomics reference maps to interpret regulatory variants in tissue-specific chromatin and epigenomic contexts.
- enables ← Gene Ontology: tool for the unification of biology — Gene Ontology enabled the Roadmap Epigenomics analysis to assign standardized biological functions to genes linked with epigenomic states.
- enables ← Fast and accurate short read alignment with Burrows–Wheeler transform — BWA enabled efficient alignment of high-throughput sequencing reads used to build Roadmap Epigenomics chromatin, methylation, and transcriptome maps.
- enables ← Mapping and quantifying mammalian transcriptomes by RNA-Seq — RNA-seq transcriptome quantification enabled Roadmap Epigenomics to integrate gene expression with chromatin and DNA methylation profiles.