III-CXT: Collaborative Research: A High-Throughput Approach to the Assignment of Orthologous Genes Based on Genome Rearrangement

III-CXT：协作研究：基于基因组重排的直系同源基因分配的高通量方法

• 批准号: 0710945
• 负责人: Liqing Zhang
• 金额: $ 19万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0710945&HistoricalAwards=false
• 关键词: III; CXT; Collaborative; Research; Throughput

Abstract Orthologous genes, or orthologs, are genes in different species that have evolved directly from a common ancestral gene. Genome-scale assignment of orthologs is a fundamental and challenging problem in computational biology, and has a wide range of applications in comparative genomics and functional genomics. This project continues the development of the parsimony approach for assigning orthologs between closely related genomes which essentially attempts to transform one genome into another by the smallest number of genome rearrangement events including reversal, translocation, fusion, and fission, as well as gene duplication events. The project addresses three key algorithmic problems including (i) signed reversal distance with duplicates, (ii) signed transposition distance with duplicates, and (iii) minimum common string partition. Efficient solutions to each of these problems are combined and incorporated into a software system for ortholog assignment, called MSOAR. The project encompasses genome-wide analysis of orthologous (and paralogous) relationships on the human and mouse genomes to valdiate the approach, and more importantly, to address several important evolutionary biological questions including the characterization of gains and losses of duplicated genes in the two genomes, the elucidation of gene movements in one genome with respect to the other genome, and the quantification of different mechanisms of gene duplication. Intellectual merit. The parsimony approach presents a novel method for performing genome-wide ortholog assignment that takes into account both gene sequences and locations. The above algorithmic problems are new in the literature and their solutions likely require the introduction of novel algorithm design and analysis techniques. The questions regarding gene duplication and quantification of the duplication mechanisms in model species are of fundamental importance in evolutionary biology. Broader impact. As ortholog assignment is a fundamental problem in comparative genomics and has become a routine practice in almost all areas of genomics, MSOAR will find itself a wide range of applications in biology and genomics. Moreover, the research will provide the training opportunity for two computer science graduate students in the interdisciplinary field of computational biology. Information concerning this NSF project will be provided at the website: http://msoar.cs.ucr.edu/

摘要 直向同源基因，或直向同源物，是不同物种中直接从共同祖先基因进化而来的基因。直向同源物的基因组规模分配是计算生物学中的一个基本且具有挑战性的问题，并且在比较基因组学和功能基因组学中具有广泛的应用。该项目继续开发用于在密切相关的基因组之间分配直系同源物的简约方法，该方法本质上试图通过最少数量的基因组重排事件（包括逆转、易位、融合和裂变以及基因复制事件）将一个基因组转化为另一个基因组。该项目解决了三个关键算法问题，包括（i）具有重复项的有符号反转距离，（ii）具有重复项的有符号转置距离，以及（iii）最小公共字符串分区。这些问题的有效解决方案被组合并纳入一个用于直向同源分配的软件系统中，称为 MSOAR。该项目包括对人类和小鼠基因组上的直系同源（和旁系同源）关系进行全基因组分析，以验证该方法，更重要的是，解决几个重要的进化生物学问题，包括两个基因组中重复基因的获得和丢失的特征，阐明一个基因组相对于另一个基因组的基因运动，以及不同基因复制机制的量化。智力上的优点。简约方法提出了一种执行全基因组直系同源分配的新方法，该方法考虑了基因序列和位置。上述算法问题在文献中是新的，它们的解决方案可能需要引入新颖的算法设计和分析技术。关于模型物种中基因复制和复制机制量化的问题在进化生物学中具有根本重要性。更广泛的影响。由于直系同源分配是比较基因组学中的一个基本问题，并且已成为几乎所有基因组学领域的常规实践，因此 MSOAR 将在生物学和基因组学中得到广泛的应用。此外，该研究还将为两名计算机科学研究生提供计算生物学跨学科领域的培训机会。有关该 NSF 项目的信息将在网站上提供：http://msoar.cs.ucr.edu/