Deep mutational scanning: assessing protein function on a massive scale

• Published in: Trends in biotechnology (Regular ed.) Vol. 29; no. 9; pp. 435 - 442
• Main Authors: Araya, Carlos L, Fowler, Douglas M
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Ltd 01.09.2011; Cell Press; Elsevier Limited
• Subjects: Amino Acid Sequence; Assessments; Base Sequence; Biological and medical sciences; Biotechnology; Cancer; Cloning; Computational Biology; Deoxyribonucleic acid; Disease; Diverse techniques; DNA; Functional analysis; Fundamental and applied biological sciences. Psychology; Gene expression; Growth hormones; high-throughput nucleotide sequencing; High-Throughput Screening Assays; Internal Medicine; Methods; Methods. Procedures. Technologies; Molecular and cellular biology; Molecular Sequence Data; Mutagenesis; Mutagenesis, Site-Directed; mutants; Mutation; Protein engineering; Protein folding; Proteins; Proteins - chemistry; Proteins - genetics; Scanning; Sequencing; Trends; Utilities; Review; Mutation; Mutagenesis; High-throughput sequencing; Structure function relationship; Protein
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2011.04.003

Analysis of protein mutants is an effective means to understand their function. Protein display is an approach that allows large numbers of mutants of a protein to be selected based on their activity, but only a handful with maximal activity have been traditionally identified for subsequent functional analysis. However, the recent application of high-throughput sequencing (HTS) to protein display and selection has enabled simultaneous assessment of the function of hundreds of thousands of mutants that span the activity range from high to low. Such deep mutational scanning approaches are rapid and inexpensive with the potential for broad utility. In this review, we discuss the emergence of deep mutational scanning, the challenges associated with its use and some of its exciting applications.