ABI Development: CAFE for very large comparative genomic datasets

基因组测序项目揭示了物种之间基因的频繁得失。这些变化已被证明是形态、生理和行为差异的原因，并有助于在自然界中观察到的多样性。测序技术的进步使新的基因组数据以比以往更快的速度获得。随着拥有测序基因组的物种数量的增加，希望利用这些宝贵资源的研究人员的数量也会增加。他们将来自广泛的生物学领域，并拥有同样广泛的计算工具经验。CAFE(基因家族进化的计算分析)是一个软件包，使研究人员能够更好地了解基因的得失速度。该项目将产生一个CAFE版本，通过实现新的生物发现来增加国家基础设施，使在许多领域工作的科学家受益。CAFE将是科学教育中的一个有用工具，还将改进和加速生物学研究，这些研究有望产生多种社会效益，包括了解重要生物表型的遗传基础。一个积极的推广和信息传播计划将确保从事研究教育的研究人员和教职员工意识到CAFE并能够有效地使用它，并将促进一个精通技术的21世纪生物研究社区的发展。基因家族的研究在基因调控、人类疾病和进化基因组学等许多研究领域都是必不可少的。CAFE通过提供一种在系统发育过程中分析基因得失的可能性方法，使这些研究和其他前沿领域的研究得以实现。这种方法已经被证明对大多数生物体目前可用的容易出错的基因组组合很好地工作，并且在一次分析数十个基因组时也是如此。该项目将把这些能力扩展到数百或数千个基因组。为了实现这一目标，将重新设计CAFE实施的几种最大似然方法。这些变化将包括允许基因家族之间的比率差异，优化树的似然计算，以及改进这些计算所使用的几种概率分布的规范。代码的质量将通过软件工程的最佳实践和开发更好、更快、更可伸缩的超级计算机软件版本来提高。所有软件将在www.Indiana.edu/~hahnlab/上提供。

Genome sequencing projects have revealed frequent gains and losses of genes between species. These changes have been shown to be responsible for morphological, physiological, and behavioral differences, and to contribute to the diversity observed in nature. Advances in sequencing technology are making new genome data available at faster rates than ever before. As the number of species with sequenced genomes grows, so will the number of researchers wanting to take advantage of these valuable resources. They will come from a wide range of biological fields, and have an equally wide range of experience with computational tools. CAFE (Computational Analysis of gene Family Evolution) is a software package that allows researchers to better understand rates of gene gain and loss. This project will result in a version of CAFE that adds to the national infrastructure by enabling new biological discoveries to the benefit of scientists working in many fields. CAFE will be a useful tool in science education, and will also improve and accelerate biological research that can be expected to have multiple societal benefits, including understanding the genetic basis for important biological phenotypes. A vigorous outreach and information dissemination plan will ensure that researchers and faculty engaged in research education are aware of CAFE and able to use it effectively, and will promote the development of a technology-savvy 21st century biology research community.Studies of gene families are essential to a number of research areas, including gene regulation, human disease, and evolutionary genomics. CAFE enables these and other studies into cutting-edge areas by providing a likelihood method for analyzing gene gain and loss over a phylogeny. This method has been shown to work well with the error-prone genome assemblies currently available for most organisms, as well as when analyzing dozens of genomes at a time. This project will extend these capabilities to hundreds or thousands of genomes. To accomplish this goal, several of the maximum likelihood methodologies implemented by CAFE will be re-designed. These changes will include allowing rate variation among gene families, optimizing likelihood calculations on trees, and improving specification of several probability distributions used by these calculations. The quality of the code will be enhanced through best practices in software engineering and the development of better, faster, and more scalable supercomputer versions of the software. All software will be available at www.indiana.edu/~hahnlab/.