PROTEIN FUNCTIONAL ANALYSIS BY ENRICHMENT AND DEPLETION OF VARIANTS (ENRICH)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Measuring the consequences of mutation in a protein is critical to understand how proteins function. These measurements are essential in such applications as protein engineering, drug development, protein design and genomics. Recently, high-throughput sequencing has been coupled to assays of protein activity, enabling the analysis of large numbers of mutations in parallel. We developed Enrich, a tool for analyzing such deep mutational scanning data. Enrich identifies all unique mutants (variants) of a protein in high-throughput sequencing data sets, and uses the frequency of each variant before and after selection to calculate an enrichment ratio. Enrich is designed to function in a high-performance computing environment because the computational demands associated with comparing multiple large sets of mutational data are high. Enrich provides an interactive interface to guide users. It generates user-accessible output for downstream analyses as well as several visualizations of the effects of mutation on function, thereby allowing the user to rapidly quantify and comprehend sequence-function relationships.