Wei Huijin, Li Xianghua
Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, Zhejiang, China.
Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Front Genet. 2023 Jan 12;14:1087267. doi: 10.3389/fgene.2023.1087267. eCollection 2023.
Unveiling how genetic variations lead to phenotypic variations is one of the key questions in evolutionary biology, genetics, and biomedical research. Deep mutational scanning (DMS) technology has allowed the mapping of tens of thousands of genetic variations to phenotypic variations efficiently and economically. Since its first systematic introduction about a decade ago, we have witnessed the use of deep mutational scanning in many research areas leading to scientific breakthroughs. Also, the methods in each step of deep mutational scanning have become much more versatile thanks to the oligo-synthesizing technology, high-throughput phenotyping methods and deep sequencing technology. However, each specific possible step of deep mutational scanning has its pros and cons, and some limitations still await further technological development. Here, we discuss recent scientific accomplishments achieved through the deep mutational scanning and describe widely used methods in each step of deep mutational scanning. We also compare these different methods and analyze their advantages and disadvantages, providing insight into how to design a deep mutational scanning study that best suits the aims of the readers' projects.
揭示遗传变异如何导致表型变异是进化生物学、遗传学和生物医学研究中的关键问题之一。深度突变扫描（DMS）技术使得数以万计的遗传变异能够高效且经济地映射到表型变异上。自从大约十年前首次系统引入以来，我们见证了深度突变扫描在许多研究领域的应用并带来了科学突破。此外，由于寡核苷酸合成技术、高通量表型分析方法和深度测序技术，深度突变扫描每个步骤中的方法都变得更加通用。然而，深度突变扫描的每个具体可能步骤都有其优缺点，一些局限性仍有待进一步的技术发展。在此，我们讨论通过深度突变扫描取得的近期科学成就，并描述深度突变扫描每个步骤中广泛使用的方法。我们还比较这些不同方法并分析其优缺点，为如何设计最适合读者项目目标的深度突变扫描研究提供见解。
