CAREER: New Technologies for Querying Pathway Databases

与大多数生物信息学数据不同，如DNA序列和蛋白质结构，通路显示了不同生物化学实体的相互作用。因此，每个实体或子路径都可以在其路径中具有路径没有它就无法实现的功能。制定这些函数带来了令人兴奋的计算挑战。这一建议为有效和准确的路径计算分析开发了算法。实现这一目标的第一步是建立路径和子路径功能的数学模型。这一建议将子通路的功能定义为它对整个通路的稳定状态的贡献。计算这一贡献是一个困难的问题，尤其是对于基因调节途径而言。现有的方法可以计算代谢途径的这一点，但它们甚至不能扩展到中等大小的基因调节途径。该方案开发了计算函数的有效方法，寻找具有期望函数的子路径是一个具有挑战性的问题。没有明确的方法来使用现有工具搜索具有所需功能的地铁。该方案开发了有效的算法来搜索具有所需功能的子路径。该方案更进一步，并开发了数学上合理的算法来比较两条路径，以使映射的实体在功能上、同源上和拓扑上相似。该方案还探索了生物途径数据库的特征和基于参考的索引结构。有关该项目的更多信息可在项目网页上找到：http://bioinformatics.cise.ufl.edu/

Unlike most bioinformatics data, such as DNA sequences and proteinstructures, pathways show the interactions of different bio-chemicalentities. Thus, each entity or subpathway can have a function in itspathway that the pathway can not realize without it. Formulating thesefunctions presents exciting computational challenges. This proposal develops algorithms for efficient and accuratecomputational analysis of pathways. The first step in achieving thisgoal is to build a mathematical model for functions of pathways andsubpathways. This proposal defines the function of a subpathway as itscontribution to the steady state of the entire pathway. Computing thiscontribution is a difficult problem especially for gene regulatorypathways. Existing methods can compute this for metabolic pathways,but they do not scale to even medium sized gene regulatorypathways. This proposal develops efficient methods for computingfunction.Finding the subpathway that has a desired function is a challengingproblem. There is no clear way of searching for subpathways withdesired functions using existing tools. This proposal developsefficient algorithms for searching subpathways with desired function.This proposal takes this one step further, and develops mathematicallysound algorithms for comparing two pathways so that the entities thatmap are functionally, homologically and topologically similar. Thisproposal also explores feature and reference-based index structuresfor biological pathway databases.Further information on the project can be found at the project webpage: http://bioinformatics.cise.ufl.edu/