The Bologna Annotation Resource: a non-hierarchical method for the functional and structural annotation of protein sequences relying on a comparative large-scale genome analysis

Protein sequence annotation is a major challenge in the postgenomic era. Thanks to the availability of complete genomes and proteomes, protein annotation has recently taken invaluable advantage from cross-genome comparisons. In this work, we describe a new non hierarchical clustering procedure characterized by a stringent metric which ensures a reliable transfer of function between related proteins even in the case of multidomain and distantly related proteins. The method takes advantage of the comparative analysis of 599 completely sequenced genomes, both from prokaryotes and eukaryotes, and of a GO and PDB/SCOP mapping over the clusters. A statistical validation of our method demonstrates that our clustering technique captures the essential information shared between homologous and distantly related protein sequences. By this, uncharacterized proteins can be safely annotated by inheriting the annotation of the cluster. We validate our method by blindly annotating other 201 genomes and finally we develop BAR (the Bologna Annotation Resource), a prediction server for protein functional annotation based on a total of 800 genomes (publicly available at http://microserf.biocomp.unibo.it/bar/).