A Survey of Computational Methods for Protein Function Prediction

Rapid advances in high-throughout genome sequencing technologies have resulted in millions of protein-encoding gene sequences with no functional characterization. Automated protein function annotation or prediction is a prime problem for computational methods to tackle in the post-genomic era of big molecular data. While recent community-driven experiments demonstrate that the accuracy of function prediction methods has significantly improved, challenges remain. The latter are related to the different sources of data exploited to predict function, as well as different choices in representing and integrating heterogeneous data. Current methods predict function from a protein’s sequence, often in the context of evolutionary relationships, from a protein’s three-dimensional structure or specific patterns in the structure, from neighbors in a protein–protein interaction network, from microarray data, or a combination of these different types of data. Here we review these methods and the state of protein function prediction, emphasizing recent algorithmic developments, remaining challenges, and prospects for future research.