Modeling gene regulation from paired expression and chromatin accessibility data
Modeling gene regulation from paired expression and chromatin accessibility data
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根据配对表达和染色质可及性数据对基因调控进行建模
DOI：
10.1073/pnas.1704553114
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发表时间：
2017-06-20
影响因子：
11.1
通讯作者：
Wong, Wing Hung
中科院分区：
文献类型：
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作者：
Duren, Zhana;Chen, Xi;Wong, Wing Hung
关于基因表达、染色质状态和转录因子（TF）结合位置的全基因组数据集的快速增加为解释基因组和表观基因组中编码的信息提供了令人兴奋的机会。这项任务可能是具有挑战性的，因为它需要联合建模的上下文特异性激活的顺式调控元件（RE）和相关的调控因子的转录的影响。为了应对这一挑战，我们提出了一种基于不同细胞环境中配对表达和染色质可及性（PECA）数据的统计方法。在我们的方法中，我们建模（i）本地化的RE的染色质调节剂（CR）的基础上，它们与序列特异性TF的相互作用，（ii）的激活RE由于CR是本地化的，和（iii）的TF结合到激活的RE上的靶基因（TG）的转录的影响。由PECA推断的转录调控网络提供了一个详细的视图，反式和顺式调控元件如何共同作用，以特定的方式影响基因表达。我们通过分析小鼠DNA元件百科全书（ENCODE）的配对表达和可访问性数据来说明这种方法的可行性，并探索所得到的模型的各种应用。
The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans-and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.