Development and Maintenance of PANTHER Software

描述：蛋白质序列同源性（即，来自一个共同的祖先序列）可能是最广泛使用的工具，用于注释基因的假定功能。同源蛋白通常共享从共同祖先遗传而来的功能，因此，如果一种蛋白的功能已经通过实验确定，那么它的同源蛋白的功能通常可以（但并不总是）推断为相同。基于同源性的推断使得实验可处理的模式生物（如大肠杆菌、酵母、果蝇、秀丽隐杆线虫和小鼠）的功能数据可以应用于其他生物，尤其是人类。在过去的几年中，主要使用基因本体论（Gene Ontology， GO），关于蛋白质功能和编码它们的基因的结构化、可计算的数据量急剧增加。这些数据中最有用的是由生物学家在阅读了科学文献中的论文后手工输入的。本提案的目标是利用这些文献衍生的本体注释，以精心策划和结构化的方式使用它们，作为在其他生物体中推断注释的基础。我们将利用和扩展我们小组开发的现有软件，开发一个可访问网络的环境，用于在进化关系的背景下管理GO术语，并将数据与生物途径数据和数据标准联系起来。我们将把软件集成到当前的GO术语注释项目中，并支持跨GO和路径本体管理工作以及他们所服务的生物医学研究人员社区的广泛数据交换和传播计划。公共卫生相关性：目前的研究项目提供了一种具有成本效益的、准确的方法，用于从广泛的、经过充分研究的物种中获取基于实验的基因信息，并将这些信息应用于理解人类生物学、遗传学和疾病。这一方法的结果将以人和计算机都可访问的格式广泛地提供给研究人员和公众。

DESCRIPTION: Protein sequence homology (i.e., descent from a common ancestral sequence) is perhaps the most widely used tool for annotating the putative functions of genes. Homologous proteins often share functions inherited from the common ancestor, so if the function of one protein has been experimentally determined, the function of its homologues can often, but not always, be inferred to be the same. Homology-based inference allows functional data from experimentally tractable model organisms (such as E. coli, yeast, Drosophila, C. elegans and the mouse) to be applied to other organisms, most notably humans. The past several years have seen a dramatic increase in the amount of structured, computationally accessible data available on the functions of proteins and the genes that encode them, primarily using the Gene Ontology (GO). The most useful of these data have been manually entered (}curated}) by a biologist after reading papers in the scientific literature. The goal of this proposal is to leverage these literature-derived ontology annotations by using them, in a carefully curated and structured manner, as the basis for inferred annotations in other organisms. We will utilize and extend existing software developed in our groups to develop a web-accessible environment for curation of GO terms in the context of evolutionary relationships, and link the data to biological pathway data and data standards. We will integrate the software into current GO term annotation projects, and support a broad data ex- change and dissemination plan across GO and pathway ontology curation efforts and the communities of bio- medical researchers they serve. PUBLIC HEALTH RELEVANCE: The current research project provides a cost-effective, accurate methodology for taking experimentally based information about genes in a wide range of well-studied species, and applying this information to understanding human biology, genetics and disease. The results from this methodology will be made broadly available to both researchers and the public, in formats accessible to both people and computers.