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Background  Proximity-based methods and co-evolution-based phylogenetic profiles methods have been successfully used for the identification of functionally related genes. Proximity-based methods are effective for physically clustered genes while the phylogenetic profiles method is effective for co-occurring gene sets. However, both methods predict many false positives and false negatives. In this paper, we propose the Gene Cluster Profile Vector (GCPV) method, which combines these two methods by using phylogenetic profiles of whole gene clusters. The GCPV method is, currently, the only genome comparison based method that allows for the characterization of relationships between gene clusters based profiles of individual genes in clusters.    Results  The GCPV method groups together reasonably related operons in  E. coli  about 60% of the time. The method is not sensitive to the choice of a reference genome set used and it outperforms the conventional phylogenetic profiles method. Finally, we show that the method works well for predicted gene clusters from  C. crescentus  and can serve as an important tool not only for understanding gene function, but also for elucidating mechanisms of general biological processes.    Conclusions  The GCPV method has shown to be an effective and robust approach to the prediction of functionally related gene sets from proximity-based gene clusters or operons.

Gene Cluster Profile Vectors: a method to infer functionally related gene sets by grouping proximity-based gene clusters