title: Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks.
abstract: BACKGROUND
  To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees.
  
  
  RESULTS
  To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes.
  
  
  CONCLUSIONS
  By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway structures using meta-level information rather than sequence information. This method may yield further information about biological evolution, such as the history of horizontal transfer of each gene, by studying the detailed structure of the phylogenetic tree constructed by the kernel-based method.
authors.affiliation: Department of Pharmacology, Inje University College of Medicine, Busan, 614-735, Korea. o@biophilos.org
authors.forename: S June
authors.initials: SJ
authors.lastname: Oh
authors.forename: Je-Gun
authors.initials: JG
authors.lastname: Joung
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Chang
authors.forename: Byoung-Tak
authors.initials: BT
authors.lastname: Zhang
mesh_terms: D019843:Archaeal Proteins / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D019766:Genes, Archaeal; D006019:Glycolysis; D008660:Metabolism; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D010802:Phylogeny; D040901:Proteomics / Q000379:methods
chemical_list: D019843:Archaeal Proteins