ABI Innovation: Co-evolution of domains, genes and species: models, algorithms, and software

ABI 创新：领域、基因和物种的共同进化：模型、算法和软件

• 批准号: 1262593
• 负责人: Marie Dannie Durand
• 金额: $ 71.76万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1262593&HistoricalAwards=false
• 关键词: ABI; Innovation; Co; evolution; domains

An award is made to Carnegie Mellon University to develop evolutionary models, algorithms, and software for multidomain protein families. These families evolve through the insertion, duplication, and deletion of domains, sequences that encode discrete structural units that are the building blocks of protein function. The emergence of novel domain combinations drives the evolution of functional variation and interaction specificity in protein families that perform core molecular functions. Multidomain families are of central importance throughout life. In bacteria, multidomain families encode the two-component kinase signaling systems that are the back-bone of cellular communication. In eukaryotes, multidomain families are implicated in tissue repair, cell death, inflammation response, antigen recognition, and innate immunity. This project will develop a computational framework for reconstructing the evolutionary history of a multidomain family, including the domain events that gave rise to present-day proteins, the ancestral domain architectures from which they evolved, and a tree describing the history of the family as a whole. This new framework will comprise a formal, event-based model of multidomain family evolution; algorithms for inferring domain events and the ancestral domain content of a given family; and an implementation of these algorithms in prototype software for inference and visualization of multidomain protein histories. Because this approach considers domain sequence, as well as domain content, and incorporates an explicit model of events, it promises a dramatic increase in accuracy and detail. The results of this project will enable evolutionary biologists to investigate the processes of protein evolution, bench biologists to identify appropriate experimental targets, and cell biologists to complement experimental results with evolutionary analyses. This project will contribute to educational resources through the development of teaching materials on multidomain evolution for an undergraduate course, a graduate course, and a workshop on "Developing Bioinformatics Programs at Minority Schools." This one week workshop is part of a Pittsburgh Supercomputing Center initiative to develop new bioinformatics programs at minority-serving institutions. This project will also provide research training for undergraduate and graduate students at the interface between biology and computer science.

卡内基梅隆大学被授予为多结构域蛋白质家族开发进化模型、算法和软件的奖项。这些家族通过插入、复制和删除结构域来进化，结构域是编码作为蛋白质功能构建块的离散结构单位的序列。新结构域组合的出现推动了执行核心分子功能的蛋白质家族的功能变异和相互作用专一性的进化。多域家庭在一生中都是至关重要的。在细菌中，多结构域家族编码双组分的激酶信号系统，这些信号系统是细胞通讯的骨架。在真核生物中，多结构域家族与组织修复、细胞死亡、炎症反应、抗原识别和先天免疫有关。该项目将开发一个计算框架，用于重建一个多结构域家族的进化史，包括导致今天蛋白质产生的结构域事件、它们从中进化的祖先结构域结构，以及描述该家族作为一个整体的历史的树。这个新的框架将包括一个正式的、基于事件的多结构域家族进化模型；用于推断特定家族的结构域事件和祖先结构域内容的算法；以及在用于推断和可视化多结构域蛋白质历史的原型软件中实现这些算法。由于这种方法考虑了域序列以及域内容，并结合了事件的显式模型，因此它有望在准确性和细节方面显著提高。该项目的结果将使进化生物学家能够研究蛋白质进化的过程，使长凳生物学家能够确定适当的实验目标，使细胞生物学家能够用进化分析来补充实验结果。该项目将通过为本科生课程、研究生课程和“在少数民族学校开发生物信息学课程”的研讨会开发多领域进化的教材，为教育资源做出贡献。这个为期一周的研讨会是匹兹堡超级计算中心计划的一部分，该计划旨在为少数族裔服务的机构开发新的生物信息学项目。该项目还将在生物学和计算机科学之间为本科生和研究生提供研究培训。