Automated interpretation of metabolic capacity from genome and metagenome sequences

Abstract

The KEGG pathway maps are widely used as a reference data set for inferring high-level functions of the organism or the ecosystem from its genome or metagenome sequence data. The KEGG modules, which are tighter functional units often corresponding to subpathways in the KEGG pathway maps, are designed for better automation of genome interpretation. Each KEGG module is represented by a simple Boolean expression of KEGG Orthology (KO) identifiers (K numbers), enabling automatic evaluation of the completeness of genes in the genome. Here we focus on metabolic functions and introduce reaction modules for improving annotation and signature modules for inferring metabolic capacity. We also describe how genome annotation is performed in KEGG using the manually created KO database and the computationally generated SSDB database. The resulting KEGG GENES database with KO (K number) annotation is a reference sequence database to be compared for automated annotation and interpretation of newly determined genomes.

Keywords

metabolic pathway / functional module / genome annotation / genome interpretation / KEGG database

References

[1] Kanehisa, M., Goto,S., Sato, Y., Furumichi, M. and Tanabe, M. (2012) KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res., 40, D109-D114

[2] Gene Ontology Consortium. (2013) Gene Ontology annotations and resources. Nucleic Acids Res., 41, D530-D535

[3] Papin, J. A., Reed,J. L. and Palsson, B. O. (2004) Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. Trends Biochem. Sci., 29, 641-647

[4] Ravasz, E., Somera, A. L., Mongru, D. A., Oltvai, Z. N. and Barabási, A. L. (2002) Hierarchical organization of modularity in metabolic networks. Science, 297, 1551-1555

[5] Schuster, S., Pfeiffer, T., Moldenhauer, F., Koch, I. and Dandekar, T. (2002) Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae. Bioinformatics, 18, 351-361

[6] Yamada, T., Kanehisa, M. and Goto, S. (2006) Extraction of phylogenetic network modules from the metabolic network. BMC Bioinformatics, 7, 130

[7] Ogata, H., Fujibuchi, W., Goto, S. and Kanehisa, M. (2000) A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters. Nucleic Acids Res., 28, 4021-4028

[8] Muto, A., Kotera, M., Tokimatsu, T., Nakagawa, Z., Goto,S. and Kanehisa, M. (2013) Modular architecture of metabolic pathways revealed by conserved sequences of reactions. J. Chem. Inf. Model., 53, 613-622

[9] Kanehisa, M. (2013) Chemical and genomic evolution of enzyme-catalyzed reaction networks. FEBS Lett.,

[10] Maeder, D. L., Weiss,R. B., Dunn, D. M., Cherry, J. L., González, J. M., DiRuggiero, J. and Robb, F. T. (1999) Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P. horikoshii inferred from complete genomic sequences. Genetics, 152, 1299-1305

[11] Pruitt, K. D., Tatusova, T., Brown, G. R. and Maglott, D. R. (2012) NCBI Reference Sequences (RefSeq): current status, new features and genome annotation policy. Nucleic Acids Res., 40, D130-D135

[12] McDonald, A. G., Boyce,S. and Tipton, K. F. (2009) ExplorEnz: the primary source of the IUBMB enzyme list. Nucleic Acids Res., 37, D593-D597

[13] Howell, D. M., Harich, K., Xu, H. and White, R. H. (1998) α-keto acid chain elongation reactions involved in the biosynthesis of coenzyme B (7-mercaptoheptanoyl threonine phosphate) in methanogenic Archaea. Biochemistry, 37, 10108-10117

[14] Drevland, R. M., Jia,Y., Palmer, D. R. and Graham, D. E. (2008) Methanogen homoaconitase catalyzes both hydrolyase reactions in coenzyme B biosynthesis. J. Biol. Chem., 283, 28888-28896

[15] Howell, D. M., Graupner, M., Xu, H. and White, R. H. (2000) Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea. J. Bacteriol., 182, 5013-5016

[16] Fazius, F., Shelest, E., Gebhardt, P. and Brock, M. (2012) The fungal α-aminoadipate pathway for lysine biosynthesis requires two enzymes of the aconitase family for the isomerization of homocitrate to homoisocitrate. Mol. Microbiol., 86, 1508-1530

[17] Berg, I. A., Kockelkorn, D., Ramos-Vera, W. H., Say, R. F., Zarzycki, J., Hügler, M., Alber, B. E. and Fuchs, G. (2010) Autotrophic carbon fixation in archaea. Nat. Rev. Microbiol., 8, 447-460

[18] Ohashi, Y., Shi,W., Takatani, N., Aichi, M., Maeda, S., Watanabe, S., Yoshikawa, H. and Omata, T. (2011) Regulation of nitrate assimilation in cyanobacteria. J. Exp. Bot., 62, 1411-1424

[19] van der Ploeg, J. R., Eichhorn, E. and Leisinger, T. (2001) Sulfonate-sulfur metabolism and its regulation in Escherichia coli. Arch. Microbiol., 176, 1-8

[20] Liu, Y. and Whitman, W. B. (2008) Metabolic, phylogenetic, and ecological diversity of the methanogenic archaea. Ann. N. Y. Acad. Sci., 1125, 171-189

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg