![]() ![]() One part of the analytical challenge arises from the complexity of the genome and its interactions with other physical entities in the cell, but another part stems from biases and noise in the epigenomic data itself. Other areas of active research include predictive models of gene expression, promoter-enhancer interactions, polymorphism impact, replication timing, and 3D conformation (reviewed in ). Gene annotation compendia such as GENCODE are now quite mature, but cell-type-specific annotations of chromatin state remain only partially interpretable. For example, as of May 1, 2018, the ENCODE project ( ) hosts > 10,000 assays of the human genome.Īlthough these data have deepened our understanding of genome biology, we are still far from fully understanding it. Accordingly, large consortia, such as ENCODE, Roadmap Epigenomics, IHEC, and GTEx, have run many types of assays in many human cell types and cell lines, yielding thousands of epigenomic measurements for each basepair in the human genome. ![]() These assays can quantify variation in important biological phenomena across cell types. These include bisulfite sequencing for measuring methylation status, DNase-seq and ATAC-seq for measuring local chromatin accessibility, ChIP-seq for measuring protein binding and histone modifications, RNA-seq for measuring RNA expression, and Hi-C for measuring the 3D structure of the genome. In the ensuing 15 years, driven by advances in next-generation sequencing, the research community has developed many assays for characterizing the human epigenome. Clearly, answering these questions required gathering more data. Characterizing each basepair of the genome with just two bits of information-its nucleotide identity-yielded many critical insights into genome biology but also left open a host of questions about how this static view of the genome gives rise to a diversity of cell types. The Human Genome Project, at its completion in 2003, yielded an accurate description of the nucleotide sequence of the human genome but an incomplete picture of how that sequence operates within each cell. ![]()
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