14 NSFBIO:Towards detailed and consistent function prediction from protein family databases

意义重大。多亏了DNA测序技术的不断发展，我们现在知道了数千种不同生物的确切基因组成(“基因组”)，编码了数百万种不同的蛋白质。但仅仅知道这些蛋白质的化学规格(“序列”)只是第一步--最终目标是发现基因和蛋白质如何发挥功能来支持生命的多样性，以及它们中的一些如何被用于商业和生物技术应用。这个研究项目将扩展科学家和他们的学生的能力，通过将多种不同的最先进的方法结合在一起，将他们的分析从序列推进到函数。这些方法中的每一种都使用了计算(解决这种规模的问题所必需的)和广泛的生物学专业知识。接近。这个项目的一般方法是将蛋白质分类为相关蛋白质家族，并尽可能描述每个家族与功能的关系。最终目标是将相同的特定功能分配给一个家族中的所有蛋白质，或者如果该家族中存在多个功能，则分配给该家族的子集。这些关系可能非常复杂，科学上的准确性将需要应用多种不同的方法。为了实现这一目标，该项目将扩展InterPro，这是一种广泛使用的资源，它已经包含(尽管数据集成机制有限)11个不同的数据库，其中三个数据库参与了该项目：Panther、Pfam和TIGRFAM。第四个分类资源--结构-功能链接数据库(SFLD)也将并入InterPro。这四个数据库使用互补的方法来表示和描述蛋白质关系，它们将被整合在一起，以前所未有的准确性、精确度和易用性解决蛋白质功能分类的问题。由于蛋白质通常不是孤立工作的，与通路和复合体相关的额外结构注释将被添加到家族集合中，以确定基因组中存在的功能特征。这项工作的产品将用于增强科学界使用的序列分析工具，以及提供增强的教育材料，并将在http://ebi.ac.uk/interpro.网站上广泛获得

Significance. Thanks to continuing developments in DNA sequencing technology, we now know the exact genetic makeup ("genome") of thousands of different organisms, encoding millions of different proteins. But simply knowing the chemical specification (the "sequence") of these proteins is only a first step-the ultimate goal is to discover how genes and proteins function to support the diversity of life, and also how some of them can be used for commercial and biotechnology applications. This research project will expand the capability of scientists and their students, to advance their analyses from sequences to functions, by bringing together multiple different state-of-the-art approaches. Each of these approaches uses both computational (necessary to address a problem of this magnitude) and broad biological expertise. Approach. The general approach in this project is to classify proteins into families of related proteins, and, wherever possible, describe how each family relates to function. The ultimate goal is to assign the same specific function to all of the proteins in a family or to subsets of the family if more than one function is represented within the family. These relations may be very complex, and scientific accuracy will require application of multiple, diverse methods. In order to accomplish this aim, the project will expand InterPro, a widely used resource that already contains (though with limited data integration mechanisms) eleven different databases, three of which are involved in this project: PANTHER, Pfam and TIGRFAM. A fourth classification resource, the Structure-Function Linkage Database (SFLD), will also be incorporated into InterPro. These four databases use complementary methodologies to represent and describe protein relationships, which will be integrated to address the problem of protein function classification with unprecedented accuracy, precision and ease-of-use. As proteins do not generally work in isolation, additional structured annotations relating to pathways and complexes will be added to sets of families, to defined functional characteristics present in a genome. The products of this work will be used to enhance sequence analysis tools used by the scientific community, as well as to provide enhanced educational materials, and will be broadly accessible over the web at http://ebi.ac.uk/interpro.