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scGREAT:用于单细胞多组学数据的基于图形的调控元件分析工具。

scGREAT: Graph-based regulatory element analysis tool for single-cell multi-omics data.

作者信息

Liu Chaozhong, Wang Linhua, Liu Zhandong

机构信息

Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, USA.

Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, USA.

出版信息

bioRxiv. 2023 Jan 28:2023.01.27.525916. doi: 10.1101/2023.01.27.525916.

Abstract

MOTIVATION

With the development in single-cell multi-omics sequencing technology and data integration algorithms, we have entered the single-cell multi-omics era. Current multi-omics analysis algorithms failed to systematically dissect the heterogeneity within the datasets when inferring cis-regulatory events. Thus, there is a need for cis-regulatory element inferring algorithms that considers the cellular heterogeneity.

RESULTS

Here, we propose scGREAT, a single-cell multi-omics regulatory state analysis Python package with a rapid graph-based correlation measurement . The graph-based correlation method assigns each cell a local index, pinpointing specific cell groups of certain regulatory states. Such single-cell resolved regulatory state information enables the heterogeneity analysis equipped in the package. Applying scGREAT to the 10X Multiome PBMC dataset, we demonstrated how it could help subcluster cell types, infer regulation-based pseudo-time trajectory, discover feature modules, and find cluster-specific regulatory gene-peak pairs. Besides, we showed that global L index, which is the average of all local L values, is a better replacement for Pearson's r in ruling out confounding regulatory relationships that are not of research interests.

AVAILABILITY

https://github.com/ChaozhongLiu/scGREAT.

摘要

动机

随着单细胞多组学测序技术和数据整合算法的发展,我们已进入单细胞多组学时代。当前的多组学分析算法在推断顺式调控事件时,未能系统地剖析数据集中的异质性。因此,需要一种考虑细胞异质性的顺式调控元件推断算法。

结果

在此,我们提出了scGREAT,这是一个基于快速图形相关性测量的单细胞多组学调控状态分析Python软件包。基于图形的相关性方法为每个细胞分配一个局部索引,从而确定特定调控状态的特定细胞组。这种单细胞解析的调控状态信息使得该软件包能够进行异质性分析。将scGREAT应用于10X Multiome PBMC数据集,我们展示了它如何有助于亚聚类细胞类型、推断基于调控的伪时间轨迹、发现特征模块以及找到聚类特异性调控基因-峰对。此外,我们表明全局L指数(即所有局部L值的平均值)在排除不感兴趣的混杂调控关系方面,是比皮尔逊相关系数r更好的替代指标。

可用性

https://github.com/ChaozhongLiu/scGREAT

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa44/9900895/eb53d2b13e5d/nihpp-2023.01.27.525916v1-f0001.jpg

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