Protein function annotation by homology-based inference

Abstract

With many genomes now sequenced, computational annotation methods to characterize genes and proteins from their sequence are increasingly important. The BioSapiens Network has developed tools to address all stages of this process, and here we review progress in the automated prediction of protein function based on protein sequence and structure.

Figure 1

Automated strategy for assigning function to proteins. The various approaches to protein function prediction are described in the text. Both protein sequences and structures can provide information for family classification and functional inference. Sequence-based methods make use of different strategies for grouping proteins into families (for example, sequence tree construction based on clustering of all against all sequence comparisons) or they compare the target sequence with pre-compiled databases of families. When a structure is available, the whole structure can be scanned against precompiled sets of functional sites. Alternatively, fragments of the target protein can be used to identify any structural similarities in the conformation of proteins of known structure, possibly related to a molecular function. Both sequences and structures, together with protein-protein interaction data, can be used to infer interactions, which can provide functional clues. Ideally, an independent set should be used to assess the reliability of the various methods.

Box 1

Glossary of terms