RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.
RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.
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RoboCOP：从染色质可及性数据中联合计算众多因素的染色质占有率。
DOI：
10.1093/nar/gkab553
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发表时间：
2021-08-20
影响因子：
14.9
通讯作者：
Hartemink AJ
中科院分区：
文献类型：
--
作者：
Mitra S;Zhong J;Tran TQ;MacAlpine DM;Hartemink AJ
染色质是细胞核内DNA和蛋白质的紧密包装结构。不同蛋白质复合体在DNA上的排列受到基因表达的调节。因此，测量不同转录因子(TF)和核小体的结合位置和占据水平对于理解基因调控至关重要。基于抗体的检测染色质占有率的方法能够识别特定DNA结合因子的结合位置，但一次只能识别一个因子。相反，表观基因组可及性数据，如MNase-seq、DNase-seq和atac-seq，提供了对沿基因组结合的所有因子的染色质图景的洞察，但对这些因子的身份的洞察很少。在这里，我们提出了一种多变量状态空间模型RoboCop，它将染色质可及性数据与核苷酸序列相结合，针对数百种不同的因素联合计算核小体和转铁蛋白占有率的全基因组概率分数。我们将RoboCop应用于MNase-seq和ATAC-seq数据，以阐明核小体和酵母基因组中150个TF的蛋白质结合情况，并表明我们的模型比现有方法做出了更好的预测。我们还计算了镉胁迫下酵母基因组染色质的占有率，揭示了与转录调控相关的染色质动态。
Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and occupancy levels of different transcription factors (TFs) and nucleosomes is therefore crucial to understanding gene regulation. Antibody-based methods for assaying chromatin occupancy are capable of identifying the binding sites of specific DNA binding factors, but only one factor at a time. In contrast, epigenomic accessibility data like MNase-seq, DNase-seq, and ATAC-seq provide insight into the chromatin landscape of all factors bound along the genome, but with little insight into the identities of those factors. Here, we present RoboCOP, a multivariate state space model that integrates chromatin accessibility data with nucleotide sequence to jointly compute genome-wide probabilistic scores of nucleosome and TF occupancy, for hundreds of different factors. We apply RoboCOP to MNase-seq and ATAC-seq data to elucidate the protein-binding landscape of nucleosomes and 150 TFs across the yeast genome, and show that our model makes better predictions than existing methods. We also compute a chromatin occupancy profile of the yeast genome under cadmium stress, revealing chromatin dynamics associated with transcriptional regulation.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
48
作者：
Kasinathan, Sivakanthan;Orsi, Guillermo A.;Zentner, Gabriel E.;Ahmad, Kami;Henikoff, Steven
通讯作者：
Henikoff, Steven
改进的核小体定位算法 iNPS，可根据测序数据准确定位核小体
影响因子：
16.6
作者：
Chen, Weizhong;Liu, Yi;Han, Jing-Dong Jackie
通讯作者：
Han, Jing-Dong Jackie
影响因子：
64.8
作者：
Brogaard, Kristin;Xi, Liqun;Wang, Ji-Ping;Widom, Jonathan
通讯作者：
Widom, Jonathan
影响因子：
10.5
作者：
Platt, Jesse M.;Ryvkin, Paul;Johnson, F. Brad
通讯作者：
Johnson, F. Brad