The Berkeley-TIGR Phylogenomic Encyclopedia of Microbial Protein Families

蛋白质是细胞的主力；它们形成骨骼和头发的结构，在细胞之间传递信号，解除和修复DNA，并执行许多其他功能。它们是药物的目标；中国每年在蛋白质研究上的投资高达数十亿美元。蛋白质是由复杂的细胞机制从它们的基因组模板，基因中构建而成的。当基因组测序时，首先要问的问题之一（在基因被识别出来之后，但对它们的实际功能没有任何线索）是“这些基因有什么作用？”计算机科学家一直在开发方法来回答这个问题，而且方法每天都在变得越来越复杂。近年来发展起来的最令人兴奋的方法之一是一种叫做系统基因组学的新方法，它使用系统发生（进化）分析来预测蛋白质在其所属家族中的功能。正如政治学家可能会研究美国社会的变化，这些变化源于两党潜在的冲突议程，计算生物学家研究蛋白质家族如何通过不同的（通常是竞争的）进化过程进化出新的功能和结构，其中一些是为了保护基因/蛋白质功能，而另一些则是为了使新功能进化。利用这些进化的数学模型，生物学家能够相当精确地指出那些没有实验证据的基因最有可能的功能。伯克利系统基因组学小组和基因组研究所（TIGR）合作开发了第一个能够对微生物基因组进行系统基因组分析的主要生物数据库，即PhyloFacts微生物百科全书。这个独特的网络资源将包含数十万种蛋白质的预先计算的进化、结构和功能分析，旨在极大地提高微生物基因组功能注释的质量。这一强大的组合将为微生物生物学研究人员提供无与伦比的资源，并提供一个平台，使全球研究人员之间的虚拟合作成为可能。该项目的智力和科学价值体现在几个层面上。这些包括对微生物基因组进化机制的新认识和以前无法分类的基因的功能作用；详细分析和量化标注错误率；并为微生物群落的开发提供了资源。这项工作的更广泛影响将通过各种机制得到加强，包括为高中生和大学生以及其他机构的研究人员开设为期两周的系统基因组推断和微生物生物学暑期短期课程；加州大学伯克利分校的本科生和研究生使用该资源进行微生物基因组注释；以及整个微生物群落的系统基因组资源的可用性。最后，为这个项目开发的所有软件都将以开源的方式提供，这个项目的所有结果都可以免费下载给公共部门的调查人员。

Proteins are the workhorses of the cell; they form the structure of bones and hair, transmit signals between cells, unwind and repair DNA, and perform a host of other functions. They are the targets of pharmaceuticals; annual domestic investment in protein research is in the billions of dollars. Proteins are constructed by complex cellular machinery from their genomic templates, genes. When genomes are sequenced, one of the first questions asked (after the genes have been identified, but there is no clue about their actual function) is "What do these genes do?" Computer scientists have been developing methods to answer this question, and methods are getting more sophisticated daily. Among the most exciting methods developed in recent years is a new approach called phylogenomics that uses phylogenetic (evolutionary) analysis to predict the function of a protein in the context of the family to which it belongs. Just as a political scientist might study the changes in American society stemming from potentially conflicting agendas on both sides of the aisle, computational biologists study how protein families evolve novel functions and structures through disparate (and often competing) evolutionary processes, some of which act to conserve gene/protein function, while others act to enable new functions to evolve. Using these mathematical models of evolution enables biologists to pinpoint fairly precisely and accurately the most likely function of genes for which no experimental evidence may be available. The Berkeley Phylogenomics Group and The Institute for Genomic Research (TIGR) have teamed up to develop the first major biological database enabling phylogenomic analysis of microbial genomes, the PhyloFacts Microbial Encyclopedia. This unique web resource will contain pre-calculated evolutionary, structural and functional analyses for hundreds of thousands of proteins, and is designed to vastly improve the quality of functional annotation of microbial genomes. This powerful combination will provide an unparalleled resource to investigators in microbial biology, and provide a platform that will enable virtual collaborations among investigators worldwide. The intellectual and scientific merits of the project are on several levels. These include new understanding of the mechanisms underlying microbial genome evolution and the functional roles of previously unclassifiable genes; detailed analysis and quantification of annotation error rates; and the development of a resource for the microbial biology community. The broader impacts of this work will be enhanced through various mechanisms, including the development of a two-week summer short course in phylogenomic inference and microbial biology for high school and university students and investigators at other institutions; the inclusion of undergraduate and graduate students at UC Berkeley in microbial genome annotation using the resource; and the availability of a phylogenomic resource for the entire microbial biology community. Finally, all software developed for this project will be available in open source, and all results from this project will be available for download free to investigators in the public sector.