Methods and Insights from Single-Cell Expression Quantitative Trait Loci.

IF 7.7 2区 生物学 Q1 GENETICS & HEREDITY
Joyce B Kang, Alessandro Raveane, Aparna Nathan, Nicole Soranzo, Soumya Raychaudhuri
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引用次数: 0

Abstract

Recent advancements in single-cell technologies have enabled expression quantitative trait locus (eQTL) analysis across many individuals at single-cell resolution. Compared with bulk RNA sequencing, which averages gene expression across cell types and cell states, single-cell assays capture the transcriptional states of individual cells, including fine-grained, transient, and difficult-to-isolate populations at unprecedented scale and resolution. Single-cell eQTL (sc-eQTL) mapping can identify context-dependent eQTLs that vary with cell states, including some that colocalize with disease variants identified in genome-wide association studies. By uncovering the precise contexts in which these eQTLs act, single-cell approaches can unveil previously hidden regulatory effects and pinpoint important cell states underlying molecular mechanisms of disease. Here, we present an overview of recently deployed experimental designs in sc-eQTL studies. In the process, we consider the influence of study design choices such as cohort, cell states, and ex vivo perturbations. We then discuss current methodologies, modeling approaches, and technical challenges as well as future opportunities and applications.

单细胞表达定量性状基因组的方法和见解。
单细胞技术的最新进展实现了以单细胞分辨率对许多个体进行表达定量性状位点(eQTL)分析。批量 RNA 测序是对不同细胞类型和细胞状态的基因表达进行平均,与之相比,单细胞检测以前所未有的规模和分辨率捕捉单个细胞的转录状态,包括细粒度、瞬时和难以分离的细胞群。单细胞eQTL(sc-eQTL)图谱可以识别随细胞状态而变化的情境依赖性eQTL,包括一些与全基因组关联研究中发现的疾病变异共定位的eQTL。通过揭示这些eQTLs发挥作用的精确环境,单细胞方法可以揭示以前隐藏的调控效应,并准确定位疾病分子机制背后的重要细胞状态。在此,我们概述了最近在 sc-eQTL 研究中采用的实验设计。在这一过程中,我们考虑了研究设计选择的影响,如队列、细胞状态和体内外扰动。然后,我们讨论了当前的方法、建模方法、技术挑战以及未来的机遇和应用。
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来源期刊
CiteScore
14.90
自引率
1.10%
发文量
29
期刊介绍: Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.
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