Development of mathematical models to describe hepatic metabolic reactions to maintain homeostasis of endogenous metabolites

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22487
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Hiroshi 東京大学, 医学部附属病院, 教授 (80206523)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 代謝経路 / 病態 / 推定手法

Outline of Final Research Achievements

Recently, genome-scale metabolic network models, that integrate a vast amount of known information on human metabolic reactions, have been constructed to be publicly available. In addition, data comparing the transcriptomes of various organs between patients and healthy individuals have been accumulated in public databases, and these data will be useful to capture comprehensively the state changes associated with disease progression. In this study, we developed methods to extract comprehensively the metabolic pathways whose metabolic fluxes increase or decrease with disease progression by using data comparing transcriptomes in organs between patients and healthy individuals and taking into account the structure of the metabolic network, including directionality and branching.

Free Research Field

システム薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、代謝ネットワークの構造と代謝酵素の発現量変動情報に基づき、疾患に伴って代謝流束が変化すると考えられる代謝物を、従来法よりもバイアスが少なくかつ高い検出力で、包括的に抽出する手法を開発した。本研究で構築された解析手法は、代謝経路の変動する慢性疾患の病態理解や、新規創薬標的の探索などに有効に活用できると期待される。