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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 测量蛋白质突变的后果对于了解蛋白质如何发挥功能至关重要。 这些测量在蛋白质工程、药物开发、蛋白质设计和基因组学等应用中是必不可少的。最近，高通量测序已经与蛋白质活性测定相结合，从而能够并行分析大量突变。我们开发了Enrich，一种用于分析这种深度突变扫描数据的工具。 Enrich识别高通量测序数据集中蛋白质的所有独特突变体（变体），并使用选择前后每个变体的频率来计算富集率。Enrich被设计为在高性能计算环境中运行，因为与比较多个大型突变数据集相关的计算需求很高。 Enrich提供了一个交互式界面来指导用户。 它为下游分析生成用户可访问的输出，以及突变对功能影响的几种可视化，从而允许用户快速量化和理解序列-功能关系。

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.