DeNOPA: decoding nucleosome positions sensitively with sparse ATAC-seq data
DeNOPA: decoding nucleosome positions sensitively with sparse ATAC-seq data
复制标题
DeNOPA：使用稀疏 ATAC-seq 数据敏感地解码核小体位置
DOI：
10.1093/bib/bbab469
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发表时间：
2022-01-17
影响因子：
9.5
通讯作者：
Zhang，Zhihua
中科院分区：
文献类型：
--
作者：
Xu，Bingxiang;Li，Xiaoli;Zhang，Zhihua
作为基砖，核小体的动态和排列从根本上协调着染色质的高级结构，从而影响到几乎所有的核生物学过程。由于其相当简单的方法，转座酶可及染色质测序分析(ATAC-SEQ)已迅速被用作大宗细胞和单细胞水平染色质可及谱的主要工具；然而，描绘核小体本身的排列仍然是ATAC-SEQ的一个挑战。在目前的工作中，我们介绍了一个新的ATAC-SEQ分析工具包，称为基于ATAC-SEQ数据的核小体组织轮廓解码(DeNOPA)，用于预测核小体位置。评估表明，deNOPA优于最先进的工具，具有超稀疏的ATAC-SEQ数据，例如每个碱基对不超过0.5个片段。DeNOPA的显著性能是由短片段读取推动的，短片段读取占ATAC-seq文库中测序读取的近一半，通常被最先进的核小体定位工具丢弃。然而，我们发现短片段读数丰富了关于核小体位置的信息，并且使用高斯平滑从短片段和长片段读出都可以预测连接区。最后，使用deNOPA，我们发现当人类细胞对热休克刺激做出反应时，核小体组织的动态可能与顺式调节区的染色质可及性不直接耦合。我们的deNOPA为利用超稀疏ATAC-SEQ数据在核小体位置水平上分析染色质的动力学提供了一个强大的工具。
As the basal bricks, the dynamics and arrangement of nucleosomes orchestrate the higher architecture of chromatin in a fundamental way, thereby affecting almost all nuclear biology processes. Thanks to its rather simple protocol, assay for transposase-accessible chromatin using sequencing (ATAC)-seq has been rapidly adopted as a major tool for chromatin-accessible profiling at both bulk and single-cell levels; however, to picture the arrangement of nucleosomes per se remains a challenge with ATAC-seq. In the present work, we introduce a novel ATAC-seq analysis toolkit, named decoding nucleosome organization profile based on ATAC-seq data (deNOPA), to predict nucleosome positions. Assessments showed that deNOPA outperformed state-of-the-art tools with ultra-sparse ATAC-seq data, e.g. no more than 0.5 fragment per base pair. The remarkable performance of deNOPA was fueled by the short fragment reads, which compose nearly half of sequenced reads in the ATAC-seq libraries and are commonly discarded by state-of-the-art nucleosome positioning tools. However, we found that the short fragment reads enrich information on nucleosome positions and that the linker regions were predicted by reads from both short and long fragments using Gaussian smoothing. Last, using deNOPA, we showed that the dynamics of nucleosome organization may not directly couple with chromatin accessibility in the cis-regulatory regions when human cells respond to heat shock stimulation. Our deNOPA provides a powerful tool with which to analyze the dynamics of chromatin at nucleosome position level with ultra-sparse ATAC-seq data.