Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes

Huijin Wei; Xianghua Li

doi:10.3389/fgene.2023.1087267

Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes

Front Genet. 2023 Jan 12:14:1087267. doi: 10.3389/fgene.2023.1087267. eCollection 2023.

Authors

Huijin Wei¹, Xianghua Li^{1

2

3

4}

Affiliations

¹ Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, Zhejiang, China.
² Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
³ The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
⁴ Biomedical and Health Translational Centre of Zhejiang Province, Haining, Zhejiang, China.

Abstract

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.

Keywords: biotechnology; deep mutational scanning; genotype-phenotype mapping; high-throughput analysis; massively parallel mutagenesis; systems biology.

Publication types

Review

Grants and funding

XL is supported by the Young Scientists Fund of National Natural Science Foundation of China (NSFC Grant No.32100478). The study is also supported by the department (Zhejiang University-University of Edinburgh Institute) start-up funding and the seed-fund.