Deep Mutational Scanning: A Versatile Tool in Systematically Mapping Genotypes to Phenotypes
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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.
Romanowicz K, Resnick C, Hinton S, Plesa C bioRxiv. 2025; .
PMID: 39896582 PMC: 11785229. DOI: 10.1101/2025.01.23.634126.
Epitope mapping via in vitro deep mutational scanning methods and its applications.
Keen M, Keith A, Ortlund E J Biol Chem. 2024; 301(1):108072.
PMID: 39674321 PMC: 11783119. DOI: 10.1016/j.jbc.2024.108072.
Macia Valero A, Prins R, de Vroet T, Billerbeck S Methods Mol Biol. 2024; 2850():265-295.
PMID: 39363077 DOI: 10.1007/978-1-0716-4220-7_15.
Integrating Computational Design and Experimental Approaches for Next-Generation Biologics.
Son A, Park J, Kim W, Lee W, Yoon Y, Ji J Biomolecules. 2024; 14(9).
PMID: 39334841 PMC: 11430650. DOI: 10.3390/biom14091073.
Saturation mutagenesis-reinforced functional assays for disease-related genes.
Ma K, Huang S, Ng K, Lake N, Joseph S, Xu J Cell. 2024; 187(23):6707-6724.e22.
PMID: 39326416 PMC: 11568926. DOI: 10.1016/j.cell.2024.08.047.