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、速度更快。因此，毫不奇怪，可用的、完全测序的基因组数量继续以指数级的速度增长。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相同的基因(同源基因)的能力。然而，到目前为止，还没有资源来维护所有可用基因组的同源基因清单。在拥有正畸数据的数据库中，最大的一个数据库提供的覆盖范围不到现在测序的总基因组的25%。 这项提议旨在通过建立一个全面的、可扩展的直系同源基因库来填补这一空白，该库将与基因组测序的速度保持同步。研究的具体目的是： 1.构建了一种改进的同源基因检测算法，并利用该算法积累了与现有基因组数量相匹配的同源基因和相关进化距离的数据库； 2.开发一个询问平台，允许用户详细探索该比较基因组数据清单，以解决比较基因组学和其他领域的假说； 3.开发一个图形用户界面，使世界各地的任何研究生物学家都可以通过网络轻松访问。 这项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的遗传多样性模式。除了是一个庞大的同源序列和进化距离的储存库外，该资源还将是一个活跃的研究工具，能够计算尚未比较或尚未使用特定参数集进行比较的两个基因组之间的新的同源序列集。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，并确保它是“可进化的”，以允许通过参数空间进行探索，从而可能产生新的感兴趣的结果，例如推定的同源基因，除了一个小的结构域之外，这些同源基因是高度分化的。作为一个可公开扩展的存储库，该工具将通过防止重复工作来帮助加快研究的步伐--即两个物种之间的直系同源只需要为一组特定的参数计算一次。该工具还将允许不同的查询类型来解决各种生物学假说，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.