The BioGRID Database: An Open International Resource for Biological Interactions

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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.