Mapping of microbial pathways through constrained mapping of orthologous genes
Olman, V.; Hanchuan Peng; Zhengchang Su; Ying Xu
Computational Systems Bioinformatics Conference, 2004. CSB 2004. Proceedings. 2004 IEEE
Volume , Issue , 16-19 Aug. 2004 Page(s): 363 - 370
Digital Object Identifier 10.1109/CSB.2004.1332449
Summary: We present a novel computer algorithm for mapping biological pathways from one prokaryotic genome to another. The algorithm maps genes in a known pathway to their homologous genes (if any) in a target genome that is most consistent with (a) predicted orthologous gene relationship, (b) predicted operon structures, and (c) predicted co-regulation relationship of operons. Mathematically, we have formulated this problem as a constrained minimum spanning tree problem (called a Steiner network problem), and demonstrated that this formulation has the desired property through applications. We have solved this mapping problem using a combinatorial optimization algorithm, with guaranteed global optimality. We have implemented this algorithm as a computer program, called P-MAP. Our test results on pathway mapping are highly encouraging - we have mapped a number of pathways of H. influenzae, B. subtilis, H. pylori, and M. tuberculosis to E. coli using P-MAP, whose homologous pathways in E coli. are known and hence the mapping accuracy could be checked. We have then mapped known E. coli pathways in the EcoCyc database to the newly sequenced organism Synechococcus sp WHS 102, and predicted 158 Synechococcus pathways. Detailed analyses on the predicted pathways indicate that P-MAP's mapping results are consistent with our general knowledge about (local) pathways. We believe that P-MAP will be a useful tool for microbial genome annotation projects and inference of individual microbial pathways.
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