The BioGRID Database: An Open International Resource for Biological Interactions

复杂的生物体，如人类，是由数以万亿计不同类型的细胞组成的，这些细胞被组织成组织和器官。每个细胞本身都由基因组编码的数以万计的蛋白质组成；反过来，细胞的行为又受到基因和蛋白质相互作用的巨大网络的支配，这些网络几乎控制着细胞的每一项功能，无论是分裂、基因表达、细胞形状和运动、发育还是能量生产和代谢。要理解细胞的功能，无论是正常的，还是在疾病中出现错误的过程，都是困难的，因为细胞网络是如此错综复杂地相互联系，以至于很难剖析每个单独基因的贡献。当我们像在生物化学中那样单独分析这些成分时，我们对每个单独的过程都了解了很多，但不一定它们是如何协同工作的。相反，如果我们试图通过基因突变来移除谜题中的关键成分，我们可能会失去整个过程的功能，从而无法识别所讨论的基因的确切功能。不同基因的多重功能，以及细胞网络中可能出现的内在冗余，进一步混淆了这些困难。系统生物学的方法是结合许多不同类型的测量，包括生化和遗传，以了解每一个单独的蛋白质和基因的累积效应。试图了解细胞和生物体如何运作的关键第一步是跟踪细胞内数十万次的相互作用。科学文献记录了全球数千名研究人员获得的结果，他们研究了许多不同的物种。基因组序列分析以及对从酵母到人类的各种物种的特定基因功能的研究带来的深刻见解之一是，所有生物实际上都是非常密切的联系。因此，酵母细胞中的许多机制与人类细胞中的机制基本相同。因此，对酵母、蠕虫、苍蝇和植物等“模式”生物的研究已被证明在理解人类疾病方面提供了极大的信息。事实上，在一个有机体上的基本发现总是会导致对所有物种的更好的理解。一个主要的理解方法是阐明细胞的遗传和蛋白质相互作用。已经设计了各种技术来检测各种相互作用，其中许多方法现在可以以快速、高通量的方式进行。尽管发现的所有相互作用都记录在科学文献中，但出现了一个问题，因为没有这种相互作用的中央储存库，因此很难以系统的方式进行分析。为了解决这个问题，我们组建了一个由计算机程序员和生物学家组成的团队，他们为数以千计的蛋白质和基因相互作用整理科学文献，我们按各种标准系统地对这些文献进行分类，然后永久保存在一个名为BioGRID(www.thebiogrid.org)的开放访问在线数据库中。一个名为鱼鹰的相关图形界面使生物学家能够根据这些相互作用轻松地组装网络，从而推断出它们的功能。我们建议为爱丁堡大学的BioGRID数据库建立一个主要门户，并通过管理来自酵母、蠕虫、苍蝇、植物和人类细胞的基因和蛋白质相互作用来扩大BioGRID/Osprey系统的容量。我们还将开发新的软件工具，以提高BioGRID/Osprey的性能，包括建立与爱丁堡系统生物学中心其他复杂分析平台的链接。存放在BioGRID中的大型相互作用数据集将被证明对国际学术生命科学界以及生物技术和制药行业来说是无价的。

Complex organisms, such as humans, are composed of trillions of cells of many hundreds of different types, organized into tissues and organs. Each cell is itself composed of tens of thousands of proteins encoded by the genome; in turn, the cell's behavior is dictated by a vast network of gene and protein interactions that control virtually every cellular function, whether it be division, gene expression, cell shape and movement, development, or energy production and metabolism. The difficulty in understanding just how cells function, either normally, or when processes run awry in disease, is that cellular networks are so intricately interconnected that it is difficult to dissect the contribution of each individual gene. While analyzing the components individually, as in biochemistry, we learn much about each individual process, but not necessarily how they work together. Conversely, if we attempt to remove key components from the puzzle by genetic mutations, we may lose the function of the entire process, and thus not be able to discern the precise function of the gene in question. These difficulties are further confounded by the often multiple functions of different genes, and by the built in redundancies that can occur in cellular networks. The approach of systems biology is to combine many different types of measurements, both biochemical and genetic, in order to understand the cumulative effect of each individual protein and gene. A crucial first step in attempting to understand how cells and organisms function is to keep track of the many hundreds of thousands of interactions in the cell. The scientific literature records the results obtained by thousands of researchers around the globe, who study many different species. One of the profound insights to come from genome sequence analysis, as well as from the study of specific gene functions in species that range from yeast to humans, is that all organisms are in fact very closely related. Thus, many of the mechanisms that operate in a yeast cell are fundamentally the same as those in a human cell. For this reason, the study of 'model' organisms, such as yeast, worms, flies and plants, has proven extremely informative in understanding, for example, human disease. Indeed, fundamental discoveries in one organism invariably lead to a better understanding of all species. A primary means of understanding is to elucidate the genetic and protein interactions of the cell. A variety of techniques have been devised to detect various interactions, and many of these methods can now be carried out in a rapid high throughput fashion. Although all interactions discovered are recorded in the scientific literature, a problem has emerged in that there is no central repository for such interactions, which are thus difficult to analyze in a systematic manner. To solve this issue, we have assembled a team of computer programmers and biologists who curate the scientific literature for thousands of protein and genetic interactions, which we systematically classify by various criteria and then house permanently in an open access on-line database called the BioGRID (www.thebiogrid.org). An associated graphical interface called Osprey enables biologists to easily assemble networks from these interactions, and thereby deduce their function. We propose to establish a primary portal for the BioGRID database at the University of Edinburgh and to expand the capacity of the BioGRID/Osprey system through the curation of gene and protein interactions from yeasts, worms, flies, plants and human cells. We will also develop new software tools to enhance the performance of BioGRID/Osprey, including building links to other sophisticated analysis platforms at the Centre for Systems Biology in Edinburgh. The large interaction datasets housed in BioGRID will prove invaluable to the international academic life sciences community and to the biotechnology and pharmaceutical industries.