Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By using IDEAS as our integrative and discriminative epigenome annotation system, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of more than 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website to aid research in genomics and hematopoiesis.

中文翻译：

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小鼠造血调控和转录景观的综合观点。


在过去的十年中，已经生成了数千个表观基因组数据集，但研究人员很难有效地利用与其项目相关的所有数据。系统整合分析可以帮助满足这一需求，VISION项目的建立是为了对造血过程中的表观基因组数据进行有效的系统整合。在这里，我们系统地整合了来自多个来源（包括各个实验室和联盟）的大量记录表观遗传特征和转录组的数据，以全面了解小鼠造血细胞类型分化的调控景观。通过使用 IDEAS 作为我们的综合和判别性表观基因组注释系统，我们可以精确且全面地同时沿着染色体和跨细胞类型识别和分配表观遗传状态。将核酸酶可及性和表观遗传状态相结合产生了一组超过 200,000 个候选顺式调控元件 (cCRE)，可有效捕获增强子和启动子。这些 cCRE 跨细胞类型的表观遗传状态的转变提供了对调节机制的见解，包括大多数谱系分化期间活性 cCRE 数量的减少、从平衡状态到活性或非活性状态的转变，以及 CTCF 结合元件的核酸酶可及性的变化。 cCRE 的表观遗传状态和基因表达的回归模型产生了一种多功能资源，可以改善对可能调节目标基因的 cCRE 的选择。这些资源可从我们的 VISION 网站获取，以帮助基因组学和造血学研究。