Universal annotation of the human genome through integration of over a thousand epigenomic datasets.
Universal annotation of the human genome through integration of over a thousand epigenomic datasets.
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通过整合一千多个表观基因组数据集对人类基因组进行通用注释。
DOI：
10.1186/s13059-021-02572-z
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发表时间：
2022-01-06
期刊：
影响因子：
12.3
通讯作者：
Ernst J
中科院分区：
文献类型：
--
作者：
Vu H;Ernst J
染色质标记的全基因组图谱，如组蛋白修饰和开放染色质位点，为注释非编码基因组提供了有价值的信息，包括识别调控元件。诸如ChromHMM的计算方法已被应用于发现和注释由同一细胞类型内的染色质标记的组合和空间模式定义的染色质状态。先前提出了一种替代的“堆叠建模”方法，该方法从多种细胞类型的数据集中联合定义染色质状态，以所有数据集为基础产生单一的通用基因组注释。尽管这种方法对于并非特定于一种细胞类型的应用具有潜在的好处，但以前仅用于小规模的专门用途。堆叠建模的大规模应用以前曾带来可伸缩性挑战。使用ChromHMM为大规模应用而增强的版本，我们应用堆叠建模方法，使用来自100多种细胞类型的1000多个数据集，生成人类基因组的通用染色质状态注释，学习到的模型表示为全栈模型。全栈模型状态显示了外部基因组注释的明显丰富，我们使用这些注释来表征每个状态。与每个细胞类型的注释相比，全堆栈注释直接区分构成和细胞类型特定的活性，并且更能预测外部基因组注释的位置。全栈ChromHMM模型提供了基因组的通用染色质状态注释和1000多个数据集的统一全局视图。我们希望这将是一个有用的资源，补充现有的每个细胞类型的注释，以研究非编码的人类基因组。网上版载有补充材料，可在10.1186/s13059-021-02572-z查阅。
Genome-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. Using 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. The 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. The online version contains supplementary material available at 10.1186/s13059-021-02572-z.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
H3K9ME3依赖性异染色质：细胞命运变化的屏障。
DOI：
10.1016/j.tig.2015.11.001
发表时间：
2016-01
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Becker JS;Nicetto D;Zaret KS
通讯作者：
Zaret KS
影响因子：
46.9
作者：
Ernst J;Kellis M
通讯作者：
Kellis M
影响因子：
64.8
作者：
Dib, C;Faure, S;Weissenbach, J
通讯作者：
Weissenbach, J
影响因子：
4.6
作者：
Amemiya, Haley M.;Kundaje, Anshul;Boyle, Alan P.
通讯作者：
Boyle, Alan P.