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Abstract A large-scale application of the “stacked modeling” approach for chromatin state discovery previously provides a single “universal” chromatin state annotation of thehumangenome based jointly on data from many cell and tissue types. Here, we produce an analogous chromatin state annotation formousebased on 901 datasets assaying 14 chromatin marks in 26 cell or tissue types. To characterize each chromatin state, we relate the states to external annotations and compare them to analogously definedhumanstates. We expect the universal chromatin state annotation formouseto be a useful resource for studying this key model organism’s genome.
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Universal annotation of the human genome through integration of over a thousand epigenomic datasets
Abstract BackgroundGenome-wide maps of chromatin marks such as histone modifications and open chromatin sites provide valuable information for annotating the non-coding genome, including identifying regulatory elements. Computational approaches such as ChromHMM have been applied to discover and annotate chromatin states defined by combinatorial and spatial patterns of chromatin marks within the same cell type. An alternative “stacked modeling” approach was previously suggested, where chromatin states are defined jointly from datasets of multiple cell types to produce a single universal genome annotation based on all datasets. Despite its potential benefits for applications that are not specific to one cell type, such an approach was previously applied only for small-scale specialized purposes. Large-scale applications of stacked modeling have previously posed scalability challenges. ResultsUsing a version of ChromHMM enhanced for large-scale applications, we apply the stacked modeling approach to produce a universal chromatin state annotation of the human genome using over 1000 datasets from more than 100 cell types, with the learned model denoted as the full-stack model. The full-stack model states show distinct enrichments for external genomic annotations, which we use in characterizing each state. Compared to per-cell-type annotations, the full-stack annotations directly differentiate constitutive from cell type-specific activity and is more predictive of locations of external genomic annotations. ConclusionsThe full-stack ChromHMM model provides a universal chromatin state annotation of the genome and a unified global view of over 1000 datasets. We expect this to be a useful resource that complements existing per-cell-type annotations for studying the non-coding human genome.
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- Award ID(s):
- 2125664
- PAR ID:
- 10361332
- Publisher / Repository:
- Springer Science + Business Media
- Date Published:
- Journal Name:
- Genome Biology
- Volume:
- 23
- Issue:
- 1
- ISSN:
- 1474-760X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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