ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

BACKGROUND: Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses. RESULTS: ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering) and pathways (e.g. pathway hole identification), to search a genome for de novo prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make de novo enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper), and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network) visualization tools can be used to get context information that is complementary to conventional KEGG map representation. CONCLUSION: ComPath is an interactive workbench for pathway reconstruction, annotation, and analysis where experts can perform various sequence, domain, context analysis, using an intuitive and interactive spreadsheet-style interface.