Single-cell gene regulation network inference by large-scale data integration.

Single-cell gene regulation network inference by large-scale data integration.
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DOI:
10.1093/nar/gkac819
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发表时间:
2022-11-28
影响因子:
14.9
通讯作者:
Wang, Chenfei
Wang, Chenfei
中科院分区:
生物学2区
文献类型:
--
作者:
Dong, Xin;Tang, Ke;Xu, Yunfan;Wei, Hailin;Han, Tong;Wang, Chenfei

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Single-cell ATAC-seq (scATAC-seq) has proven to be a state-of-art approach to investigating gene regulation at the single-cell level. However, existing methods cannot precisely uncover cell-type-specific binding of transcription regulators (TRs) and construct gene regulation networks (GRNs) in single-cell. ChIP-seq has been widely used to profile TR binding sites in the past decades. Here, we developed SCRIP, an integrative method to infer single-cell TR activity and targets based on the integration of scATAC-seq and a large-scale TR ChIP-seq reference. Our method showed improved performance in evaluating TR binding activity compared to the existing motif-based methods and reached a higher consistency with matched TR expressions. Besides, our method enables identifying TR target genes as well as building GRNs at the single-cell resolution based on a regulatory potential model. We demonstrate SCRIP’s utility in accurate cell-type clustering, lineage tracing, and inferring cell-type-specific GRNs in multiple biological systems. SCRIP is freely available at https://github.com/wanglabtongji/SCRIP.
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