Building a framework for exploration of orthologs and evolutionary distances.

描述（由申请人提供）： 近年来，基因组测序变得更容易，更便宜，更快。因此，毫不奇怪，可用的、完全测序的基因组数量继续以指数速度增长。为了跟上新数据的洪流，手头有有效的比较基因组资源是很重要的。比较基因组学方法最重要的是确定功能等同基因（直系同源物）的能力。然而，到目前为止，还没有一个资源，保持所有可用的基因组的直系同源物的库存。在拥有同源数据的数据库中，最大的数据库覆盖了目前测序的总基因组的不到25%。 该提案旨在通过建立一个全面且可扩展的直系同源物库来填补这一空白，该库将跟上基因组测序的速度。研究的具体目标是： 1.建立一个改进的直系同源物检测算法，并使用它来积累一个直系同源物和相关进化距离的数据库，该数据库与目前可用的基因组数量相匹配; 2.开发一个询问平台，使用户能够详细探索比较基因组学数据的这一清单，以解决比较基因组学和其他领域的假设; 3.开发图形用户界面，以便世界各地的任何研究生物学家都可以通过网络轻松访问。 该研究将产生一个强大而灵活的比较基因组框架，使生物学家能够在全基因组水平上探索许多生物体的遗传多样性模式。除了是一个巨大的直向同源序列和进化距离的库之外，该资源还将是一个活跃的研究工具，能够计算尚未比较的两个基因组之间的新的直向同源物组，或者尚未使用特定的参数组进行比较。这将确保资源是动态的和可扩展的，以跟上基因组测序的快速速度，并且它是“可进化的”，以允许通过参数空间进行探索，这可能会产生新的感兴趣的结果，例如除了小域之外高度发散的推定直系同源物。作为一个可公开扩展的知识库，该工具将有助于加快研究的步伐，防止重复工作-即两个物种之间的直系同源物只需要计算一次特定的参数集。该工具还将允许多种查询类型来解决各种生物学假设，有望在医学和基础科学方面带来令人兴奋的发现。

DESCRIPTION (provided by applicant): In recent years, genome sequencing has become easier, cheaper, and significantly faster. So, not surprisingly, the number of available, fully sequenced genomes continues to increase at an exponential rate. To keep pace with the flood of new data, it is important to have efficient comparative genomic resources on hand. Of chief importance to comparative genomics methods is the ability to determine functionally equivalent genes (orthologs). Yet, to date, there is no resource that maintains an inventory of orthologs for all available genomes. Of the databases that do host orthology data, the largest provides coverage for less than 25% of the total genomes now sequenced. This proposal aims to fill this gap by building a comprehensive and expandable ortholog repository that will keep pace with the rate of genome sequencing. The specific aims of the research are to: 1. Build out an improved algorithm for ortholog detection, and use this to amass a database of orthologs and associated evolutionary distances that matches the number of genomes presently available; 2. Develop an interrogation platform that allows a user to explore this inventory of comparative genomics data in detail to address hypotheses in comparative genomics and other fields; 3. Develop a graphical user interface to allow easy access by any research biologist world-wide via the Web. The research will result in a powerful and flexible comparative genomic framework to enable biologists to explore, at a whole-genomic level, patterns of genetic diversification across many organisms. In addition to being a massive repository of orthologous sequences and evolutionary distances the resource will be an active research tool capable of calculating new sets of orthologs between two genomes that have not already been compared, or that have not been compared using a particular set of parameters. This will ensure that the resource be dynamic and expandable to keep pace with the rapid rate of genome sequencing and that it be 'evolvable' to allow exploration through parameter space that may yield novel results of interest, such as putative orthologs that are highly divergent with the exception of a small domain. And as a publicly expandable repository, the tool will help to quicken the pace of research by preventing duplication of effort - i.e. orthologs between two species only need be computed once for a particular set of parameters. The tool will also allow a diversity of query types to address a variety of biological hypotheses, hopefully leading to exciting discoveries in both the medical and basic sciences.