Department of Computer Science and Engineering, University of Nevada, Reno, NV 89557.
Brief Bioinform. 2021 May 20;22(3). doi: 10.1093/bib/bbaa190.
Gene regulatory network is a complicated set of interactions between genetic materials, which dictates how cells develop in living organisms and react to their surrounding environment. Robust comprehension of these interactions would help explain how cells function as well as predict their reactions to external factors. This knowledge can benefit both developmental biology and clinical research such as drug development or epidemiology research. Recently, the rapid advance of single-cell sequencing technologies, which pushed the limit of transcriptomic profiling to the individual cell level, opens up an entirely new area for regulatory network research. To exploit this new abundant source of data and take advantage of data in single-cell resolution, a number of computational methods have been proposed to uncover the interactions hidden by the averaging process in standard bulk sequencing. In this article, we review 15 such network inference methods developed for single-cell data. We discuss their underlying assumptions, inference techniques, usability, and pros and cons. In an extensive analysis using simulation, we also assess the methods' performance, sensitivity to dropout and time complexity. The main objective of this survey is to assist not only life scientists in selecting suitable methods for their data and analysis purposes but also computational scientists in developing new methods by highlighting outstanding challenges in the field that remain to be addressed in the future development.
基因调控网络是遗传物质之间复杂的相互作用集合,决定了细胞在生物体中的发育方式以及对周围环境的反应方式。深入理解这些相互作用有助于解释细胞的功能以及预测它们对外界因素的反应。这些知识既有益于发育生物学,也有益于临床研究,如药物研发或流行病学研究。最近,单细胞测序技术的快速发展将转录组分析的极限推进到了单细胞水平,为调控网络研究开辟了全新的领域。为了利用这一新的丰富数据来源,并利用单细胞分辨率的数据,已经提出了许多计算方法来揭示标准批量测序中平均过程所隐藏的相互作用。在本文中,我们综述了 15 种用于单细胞数据的网络推断方法。我们讨论了它们的基本假设、推断技术、可用性以及优缺点。在使用模拟进行的广泛分析中,我们还评估了这些方法的性能、对缺失值的敏感性和时间复杂度。本综述的主要目的不仅是帮助生命科学家根据数据和分析目的选择合适的方法,还帮助计算科学家通过突出该领域中仍有待未来发展解决的突出挑战来开发新方法。
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