The ProPhylER Database and Web Resource

描述（由申请人提供）： 我们建议建立ProPhylER（蛋白质系统发育和进化速率）数据库作为一般研究社区可用的网络资源。ProPhylER数据库将对直系同源物和密切相关的旁系同源物的局部约束进行定量估计。约束的估计需要强大的，策划的，比对和系统发育树，ProPhylER生成的一部分，其数据库。将通过将开发的网站上的图形界面提供路线、树木和约束估计。此外，由于ProPhylER的树提供了将蛋白质编码基因及其注释与模式生物和基因组数据库相关联的自然框架，因此提出了与SGD、Flybase和UCSC浏览器的相互链接。我们预计ProPhylER将成为一个广泛使用的工具，分析功能限制和相关基因之间的系统发育关系。由于ProPhylER的数据是在蛋白质分析的关键步骤半自动生成的，因此ProPhylER的数据具有高度的可靠性，对于研究特定蛋白质的个体研究者来说，这是很难复制的。因此，最初，它将主要是有用的实验者，对他们来说，约束分析可以指导结构功能分析，对他们来说，策划的比对和系统发育树将提供一个知识库的蛋白质的兴趣。扩展ProPhylER以产生cSNP的遗传性的定量预测将扩大目标群体以包括人类遗传学家和基因组学家。随着序列数据对大多数真核生物蛋白质的限制越来越少，ProPhylER将扩展到覆盖大部分真核生物直向同源物空间，并成为通过进化关系将真核生物直向同源物和密切相关的旁系同源物联系在一起的数据库。

DESCRIPTION (provided by applicant): We propose to establish the ProPhylER (Protein Phylogeny and Evolutionary Rates) database as a web resource available to the general research community. The ProPhylER database will feature quantitative estimates of local constraint on orthologs and closely related paralogs. Estimates of constraint require robust, curated, alignments and phylogenetic trees, which ProPhylER generates as part of its dataflow. Alignments, trees, and estimates of constraint will be made available via graphical interfaces on the web site that will be developed. In addition, because ProPhylER's trees provide the natural framework for relating protein-coding genes and their annotation across model organism and genome databases, reciprocal links to SGD, Flybase, and the UCSC browser are proposed. We anticipate that ProPhylER will become a widely used tool for the analysis of functional constraint and phylogenetic relationships among related genes. Because ProPhylER's data are generated semiautomatically with curation at the critical steps in the dataflow, ProPhylER's data have a high degree of reliability that would be difficult to reproduce for individual investigators working on a particular protein. Thus, initially it will mostly be useful for experimentalists for whom analyses of constraint can guide structure function analyses, and for whom the curated alignments and phylogenetic trees will provide a knowledge base for the protein of interest. Extension of ProPhylER to generate quantitative predictions of the deleteriousness of cSNPs will expand the target community to include human geneticists and genomicists. As sequence data become less limiting for the majority of eukaryotic proteins, ProPhylER will expand to cover most of eukaryotic ortholog space and become the database that ties together eukaryotic orthologs and closely related paralogs by their evolutionary relationships.