title: Metabolome-scale de novo pathway reconstruction using regioisomer-sensitive graph alignments.
abstract: BACKGROUND
  Recent advances in mass spectrometry and related metabolomics technologies have enabled the rapid and comprehensive analysis of numerous metabolites. However, biosynthetic and biodegradation pathways are only known for a small portion of metabolites, with most metabolic pathways remaining uncharacterized.
  
  
  RESULTS
  In this study, we developed a novel method for supervised de novo metabolic pathway reconstruction with an improved graph alignment-based approach in the reaction-filling framework. We proposed a novel chemical graph alignment algorithm, which we called PACHA (Pairwise Chemical Aligner), to detect the regioisomer-sensitive connectivities between the aligned substructures of two compounds. Unlike other existing graph alignment methods, PACHA can efficiently detect only one common subgraph between two compounds. Our results show that the proposed method outperforms previous descriptor-based methods or existing graph alignment-based methods in the enzymatic reaction-likeness prediction for isomer-enriched reactions. It is also useful for reaction annotation that assigns potential reaction characteristics such as EC (Enzyme Commission) numbers and PIERO (Enzymatic Reaction Ontology for Partial Information) terms to substrate-product pairs. Finally, we conducted a comprehensive enzymatic reaction-likeness prediction for all possible uncharacterized compound pairs, suggesting potential metabolic pathways for newly predicted substrate-product pairs.
authors.affiliation: Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8582, Institute for Advanced Study, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8581, PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8582, Institute for Advanced Study, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8581, PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamanishi
authors.affiliation: Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8582, Institute for Advanced Study, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8581, PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tabei
authors.affiliation: Division of System Cohort, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8582, Institute for Advanced Study, Kyushu University, Higashi-ku, Fukuoka, Fukuoka 812-8581, PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kotera
mesh_terms: D000465:Algorithms; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*