Screening single-cell trajectories via continuity assessments for cell transition potential

作者全名："Zheng, Zihan; Chang, Ling; Li, Yinong; Liu, Kun; Mu, Jie; Zhang, Song; Li, Jingyi; Wu, Yuzhang; Zou, Liyun; Ni, Qingshan; Wan, Ying"

作者地址："[Zhang, Song] Nankai Univ, Tianjin, Peoples R China; [Li, Jingyi] Dept Rheumatol & Immunol, Chongqing, Peoples R China; [Wu, Yuzhang] Army Med Univ, Immunol Inst, Chongqing, Peoples R China; [Zou, Liyun; Ni, Qingshan] Army Med Univ, Chongqing, Peoples R China; [Wan, Ying] Army Med Univ, Biomed Anal Ctr, Chongqing, Peoples R China"

通信作者："Wan, Y (通讯作者)，Army Med Univ, Biomed Anal Ctr, 30 Gaotanyan Ave, Chongqing 400000, Peoples R China."

来源：BRIEFINGS IN BIOINFORMATICS

ESI学科分类：COMPUTER SCIENCE

WOS号：WOS:001136371500024

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：24

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：single-cell RNA sequencing; trajectory analysis; T cell memory; arthritis; acute kidney injury

摘要："Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8+T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET."

基金机构："National Key Research and Development Program of China [2021YFA1201103, 2017YTA0700404]; National Natural Science Foundation of China [81971537, 81971546, 82171787, 82241218, 31972896, 81921004]; Chongqing International Institute for Immunology [2020YJC06]"

基金资助正文："This work was supported by funding from the National Key Research and Development Program of China (2017YTA0700404) to YW, the National Natural Science Foundation of China (81971546, 82171787) and Chongqing International Institute for Immunology (2020YJC06) to L.Z., the National Natural Science Foundation of China (82241218, 31972896, 81921004) and National Key Research and Development Program of China (2021YFA1201103) to S.Z., and the National Natural Science Foundation of China (81971537) to J.L."