当前位置:科学网首页 > 小柯机器人 >详情
单细胞中多模式表达和染色质可及性的联合调控模型
作者:小柯机器人 发布时间:2022/9/8 17:10:16

美国丹娜-法伯癌症研究所Clifford A. Meyer和X. Shirley Liu共同合作近期取得重要工作进展。他们研究开发了MIRA策略,一种单细胞中多模式表达和染色质可及性的联合调控模型。该项研究成果2022年9月6日在线发表于《自然—方法学》杂志上。

研究人员介绍了MIRA策略,即用于综合调控分析的概率多模态模型,这是一种全面的方法,可以系统地对比染色体转录和可接近性,以推断沿着细胞状态轨迹驱动细胞的调控回路。MIRA利用细胞状态和单个基因位点的调控潜力建模。因此,MIRA在有效且可解释的潜在空间中表示细胞状态,推断高保真细胞状态树,确定分支点命运决定的关键调节因子,并揭示局部可及性对不同基因座转录的可变影响。应用于两个不同的多模态平台的表皮分化和胚胎大脑发育,MIRA揭示了早期发育基因受到局部染色质概况的严格调节,而终末基因命运的调节不需要广泛的染色质重塑。

据介绍,严格地比较同一个单细胞中的基因表达和染色质可及性,可以阐明这些机制的耦合或解耦合如何调控细胞的命运。

附:英文原文

Title: MIRA: joint regulatory modeling of multimodal expression and chromatin accessibility in single cells

Author: Lynch, Allen W., Theodoris, Christina V., Long, Henry W., Brown, Myles, Liu, X. Shirley, Meyer, Clifford A.

Issue&Volume: 2022-09-06

Abstract: Rigorously comparing gene expression and chromatin accessibility in the same single cells could illuminate the logic of how coupling or decoupling of these mechanisms regulates fate commitment. Here we present MIRA, probabilistic multimodal models for integrated regulatory analysis, a comprehensive methodology that systematically contrasts transcription and accessibility to infer the regulatory circuitry driving cells along cell state trajectories. MIRA leverages topic modeling of cell states and regulatory potential modeling of individual gene loci. MIRA thereby represents cell states in an efficient and interpretable latent space, infers high-fidelity cell state trees, determines key regulators of fate decisions at branch points and exposes the variable influence of local accessibility on transcription at distinct loci. Applied to epidermal differentiation and embryonic brain development from two different multimodal platforms, MIRA revealed that early developmental genes were tightly regulated by local chromatin landscape whereas terminal fate genes were titrated without requiring extensive chromatin remodeling.

DOI: 10.1038/s41592-022-01595-z

Source: https://www.nature.com/articles/s41592-022-01595-z

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex