Debajyoti Ray

BACKGROUND: Most successful computational approaches for protein function prediction integrate multiple genomics and proteomics data sources to make inferences about the function of unknown proteins. The most accurate of these algorithms have long running times, making them unsuitable for real-time protein function prediction in large genomes. As a result, the predictions of these algorithms are stored in static databases that can easily become outdated. We propose a new algorithm, GeneMANIA, that is as accurate as the leading methods, while capable of predicting protein function in real-time. RESULTS: We use a fast heuristic algorithm, derived from ridge regression, to integrate multiple functional association networks and predict gene function from a single process-specific network using label propagation. Our algorithm is efficient enough to be deployed on a modern webserver and is as accurate as, or more so than, the leading methods on the MouseFunc I benchmark and a new yeast function prediction benchmark; it is robust to redundant and irrelevant data and requires, on average, less than ten seconds of computation time on tasks from these benchmarks. CONCLUSION: GeneMANIA is fast enough to predict gene function on-the-fly while achieving state-of-the-art accuracy. A prototype version of a GeneMANIA-based webserver is available at http://morrislab.med.utoronto.ca/prototype.

BACKGROUND: Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated. RESULTS: In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%. CONCLUSION: We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized.