Metabolome-scale prediction of intermediate compounds in multistep metabolic pathways with a recursive supervised approach

Masaaki Kotera, Yasuo Tabei, Yoshihiro Yamanishi, Ai Muto, Yuki Moriya, Toshiaki Tokimatsu, Susumu Goto

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Motivation: Metabolic pathway analysis is crucial not only in metabolic engineering but also in rational drug design. However, the biosynthetic/ biodegradation pathways are known only for a small portion of metabolites, and a vast amount of pathways remain uncharacterized. Therefore, an important challenge in metabolomics is the de novo reconstruction of potential reaction networks on a metabolome-scale. Results: In this article, we develop a novel method to predict the multistep reaction sequences for de novo reconstruction of metabolic pathways in the reaction-filling framework. We propose a supervised approach to learn what we refer to as 'multistep reaction sequence likeness', i.e. whether a compound-compound pair is possibly converted to each other by a sequence of enzymatic reactions. In the algorithm, we propose a recursive procedure of using step-specific classifiers to predict the intermediate compounds in the multistep reaction sequences, based on chemical substructure fingerprints/descriptors of compounds. We further demonstrate the usefulness of our proposed method on the prediction of enzymatic reaction networks from a metabolome-scale compound set and discuss characteristic features of the extracted chemical substructure transformation patterns in multistep reaction sequences. Our comprehensively predicted reaction networks help to fill the metabolic gap and to infer new reaction sequences in metabolic pathways.

Original languageEnglish
Pages (from-to)I165-I174
Issue number12
Publication statusPublished - Jun 15 2014

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


Dive into the research topics of 'Metabolome-scale prediction of intermediate compounds in multistep metabolic pathways with a recursive supervised approach'. Together they form a unique fingerprint.

Cite this