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InferLoop: Leveraging Single-Cell Chromatin Accessibility for the Signal of Chromatin Loop

Briefings in Bioinformatics(2023)

Shanghai Jiao Tong Univ Sch Med

Cited 1|Views36
Abstract
Deciphering cell-type-specific 3D structures of chromatin is challenging. Here, we present InferLoop, a novel method for inferring the strength of chromatin interaction using single-cell chromatin accessibility data. The workflow of InferLoop is, first, to conduct signal enhancement by grouping nearby cells into bins, and then, for each bin, leverage accessibility signals for loop signals using a newly constructed metric that is similar to the perturbation of the Pearson correlation coefficient. In this study, we have described three application scenarios of InferLoop, including the inference of cell-type-specific loop signals, the prediction of gene expression levels and the interpretation of intergenic loci. The effectiveness and superiority of InferLoop over other methods in those three scenarios are rigorously validated by using the single-cell 3D genome structure data of human brain cortex and human blood, the single-cell multi-omics data of human blood and mouse brain cortex, and the intergenic loci in the GWAS Catalog database as well as the GTEx database, respectively. In addition, InferLoop can be applied to predict loop signals of individual spots using the spatial chromatin accessibility data of mouse embryo. InferLoop is available at https://github.com/jumphone/inferloop.
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Key words
chromatin structure,single-cell chromatin accessibility,single-cell 3D genome structure,single-cell multi-omics,spatial chromatin accessibility
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要点】:本研究提出InferLoop方法,利用单细胞染色质可及性数据推断染色质环强度,实现细胞类型特异性3D染色质结构的解析。

方法】:InferLoop通过将临近细胞分组进行信号增强,并采用新构建的类似于Pearson相关系数扰动的指标,利用可及性信号进行环信号的计算。

实验】:通过使用人类大脑皮层和人类血液的单细胞3D基因组结构数据,人类血液和鼠标大脑皮层的单细胞多组学数据,以及GWAS目录数据库和GTEx数据库中的基因间区定位点,严格验证了InferLoop在推断细胞类型特异性环信号、预测基因表达水平和解释基因间区定位点三个应用场景中的有效性和优越性。