Integration of sequence-similarity and functional association information can overcome intrinsic problems in orthology mapping across bacterial genomes

Abstract

Existing methods for orthologous gene mapping suffer from two general problems: (i) they are computationally too slow and their results are difficult to interpret for automated large-scale applications when based on phylogenetic analyses; or (ii) they are too prone to making mistakes in dealing with complex situations involving horizontal gene transfers and gene fusion due to the lack of a sound basis when based on sequence similarity information. We present a novel algorithm, Global Optimization Strategy (GOST), for orthologous gene mapping through combining sequence similarity and contextual (working partners) information, using a combinatorial optimization framework. Genome-scale applications of GOST show substantial improvements over the predictions by three popular sequence similarity-based orthology mapping programs. Our analysis indicates that our algorithm overcomes the intrinsic issues faced by sequence similarity-based methods, when orthology mapping involves gene fusions and horizontal gene transfers. Our program runs as efficiently as the most efficient sequence similarity-based algorithm in the public domain. GOST is freely downloadable at http://csbl.bmb.uga.edu/~maqin/GOST.