Deep Mutational Scanning: Calculating Enrichment Scores for Protein Variants from DNA Sequencing Output Files

Abstract

During a deep mutational scanning experiment, a collection of variants of a given protein is subjected to high-throughput sequencing before and after selection. The variants that perform well during selection will increase in abundance, whereas those that perform poorly will decrease. Generating a sequence–function map of a protein from a deep mutational scan requires the calculation and comparison of the enrichment scores for each protein variant, based on the results of high-throughput DNA sequencing output files. Here we describe the use of the software program Enrich, which was written specifically for the data analysis phase of a deep mutational scanning experiment.