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dFBA model of genome-scale human metabolism and its application to multi-drug combination therapy

Research Project

Project/Area Number 16H02898
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Life / Health / Medical informatics
Research InstitutionKyushu Institute of Technology

Principal Investigator

Kurata Hiroyuki  九州工業大学, 大学院情報工学研究院, 教授 (90251371)

Research Collaborator SAKAI Yasuyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords全細胞シミュレーション / 数理モデリング / システム解析 / ヒト生理学 / 薬物動態学 / 代謝 / ネットワーク / 動力学 / 肝臓 / システム生物学 / シミュレーション / 数理モデル / インスリン / 合成生物学 / 代謝ネットワーク / コンピュータシミュレーション / 数学モデル
Outline of Final Research Achievements

We have developed a detailed kinetic model of central carbon metabolism that reproduced the existing experimental data. Subsequently, we have constructed the metabolic network maps of multiple organs including blood, liver, heart, kidney, lung, brain, skeletal muscle, and adipose tissue, and built the dynamic model of the organ interaction networks to predict the time course of the metabolites concentrations and fluxes. By using the model, we predicted changes in metabolism with respect to different environmental conditions and dosages.

Academic Significance and Societal Importance of the Research Achievements

世界でもっとも正確な細胞の中心代謝モデルの動力学モデルを開発した。また、従来の薬物動態モデルにおけるブラックボックス部分をヒト代謝ネットワークモデルで表現して、ホルモンや医薬品が全身の代謝に与える影響を予測するダイナミックモデル(創薬CAD)を開発した。創薬CADは、実験費用や時間を大幅に節約する。がん代謝をメカニズムに基づいて数理的に解析するシステム生物医学への道を拓いた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (3 results)

  • [Int'l Joint Research] VU University(オランダ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Rajshahi(バングラデシュ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] PreAIP: Computational Prediction of Anti-inflammatory Peptides by Integrating Multiple Complementary Features2019

    • Author(s)
      Khatun Mst. Shamima、Hasan Md. Mehedi、Kurata Hiroyuki
    • Journal Title

      Frontiers in Genetics

      Volume: 10 Pages: 1-10

    • DOI

      10.3389/fgene.2019.00129

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Large-Scale Assessment of Bioinformatics Tools for Lysine Succinylation Sites2019

    • Author(s)
      Hasan Md. Mehedi、Khatun Mst. Shamima、Kurata Hiroyuki
    • Journal Title

      Cells

      Volume: 8 Issue: 2 Pages: 95-95

    • DOI

      10.3390/cells8020095

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved kinetic model of Escherichia coli central carbon metabolism in batch and continuous cultures2018

    • Author(s)
      Kurata Hiroyuki、Sugimoto Yurie
    • Journal Title

      J Bioscie Bioeng

      Volume: 125 Issue: 2 Pages: 251-257

    • DOI

      10.1016/j.jbiosc.2017.09.005

    • NAID

      40021471336

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long negative feedback loop enhances period tunability of biological oscillators2018

    • Author(s)
      Maeda Kazuhiro、Kurata Hiroyuki
    • Journal Title

      Journal of Theoretical Biology

      Volume: 440 Pages: 21-31

    • DOI

      10.1016/j.jtbi.2017.12.014

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel isolation method for cancer prognostic factors via the p53 pathway by a combination of in vitro and in silico analyses2018

    • Author(s)
      Kamijo Y, Kawahara K, Yoshinaga T, Kurata H, Arima K, Furukawa T.
    • Journal Title

      Oncoscience

      Volume: 5 Issue: 3-4 Pages: 88-98

    • DOI

      10.18632/oncoscience.411

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] libRCGA: a C library for real-coded genetic algorithms for rapid parameter estimation of kinetic models2018

    • Author(s)
      Maeda Kazuhiro、Boogerd Fred C.、Kurata Hiroyuki
    • Journal Title

      IPSJ Transactions on Bioinformatics

      Volume: 11 Issue: 0 Pages: 31-40

    • DOI

      10.2197/ipsjtbio.11.31

    • NAID

      130007483197

    • ISSN
      1882-6679
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] iLMS, Computational Identification of Lysine-Malonylation Sites by Combining Multiple Sequence Features2018

    • Author(s)
      Hasan Md. Mehedi、Kurata Hiroyuki
    • Journal Title

      Proceedings of IEEE 18th International Conference on Bioinformatics and Bioengineering

      Volume: 1 Pages: 1-10

    • DOI

      10.1109/bibe.2018.00077

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SIPMA: A Systematic Identification of Protein-Protein Interactions in Zea mays Using Autocorrelation Features in a Machine-Learning Framework2018

    • Author(s)
      Khatun Mst. Shamima、Hasan Md. Mehedi、Mollah Md. Nurul Haque、Kurata Hiroyuki
    • Journal Title

      Proceedings of IEEE 18th International Conference on Bioinformatics and Bioengineering

      Volume: 1 Pages: 1-10

    • DOI

      10.1109/bibe.2018.00030

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modeling and simulation of the redox regulation of the metabolism in Escherichia coli at different oxygen concentrations2017

    • Author(s)
      Matsuoka Yu、Kurata Hiroyuki
    • Journal Title

      Biotechnol Biofules

      Volume: 10 Issue: 1 Pages: 1-15

    • DOI

      10.1186/s13068-017-0867-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mathematical comparison of memory functions between mutual activation and repression networks in a stochastic environment2017

    • Author(s)
      Hasan A.B.M. Shamim Ul、Kurata Hiroyuki
    • Journal Title

      J Theor Biol

      Volume: 427 Pages: 28-40

    • DOI

      10.1016/j.jtbi.2017.05.036

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of an accurate kinetic model for the central carbon metabolism of Escherichia coli.2016

    • Author(s)
      Nusrat Jahan, Kazuhiro Maeda, Yu Matsuoka, Yurie Sugimoto, Hiroyuki Kurata.
    • Journal Title

      Microbial Cell Factories

      Volume: 15 Issue: 1 Pages: 112-112

    • DOI

      10.1186/s12934-016-0511-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] S-system-based Analysis of the Robust Properties Common to Many Biochemical Network Models2016

    • Author(s)
      Yu Matsuoka, Nusrat Jahan, Hiroyuki Kurata
    • Journal Title

      Bioprocess Biosyst Eng

      Volume: 39 Issue: 5 Pages: 735-746

    • DOI

      10.1007/s00449-016-1554-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Web application for Genetic Modification Flux with database to estimate metabolic fluxes of genetic mutants2016

    • Author(s)
      Noorlin Mohd Ali, Ryo Tsuboi, Yuta Matsumoto, Daisuke Koishi, Kentaro Inoue, Kazuhiro Maeda, and Hiroyuki Kurata
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 印刷中 Issue: 1 Pages: 111-116

    • DOI

      10.1016/j.jbiosc.2015.12.001

    • NAID

      40020886002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 代謝均等分解サイクルのReLU応答の解析2019

    • Author(s)
      倉田博之
    • Organizer
      化学工学会第84回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酵素濃度や複数炭素源が代謝に及ぼす影響を考慮した大腸菌の中心代謝モデルの開発2018

    • Author(s)
      松岡結,倉田博之
    • Organizer
      化学工学会第50回秋季大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 嫌気好気条件下での回分培養大腸菌の代謝動力学モデル2018

    • Author(s)
      松岡結, 倉田博之
    • Organizer
      化学工学会第83回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞の全代謝動力学モデルの開発2018

    • Author(s)
      倉田博之
    • Organizer
      電子情報通信学会2018年総合大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Virtual cell metabolism for systems and synthetic biology2017

    • Author(s)
      Hiroyuki Kurata
    • Organizer
      International Conference on Bioinformatics and Biostatistics for Agriculture, Health and Environment
    • Place of Presentation
      Rajshahi (Bangladesh)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] スマートセルインダストリーを指向した中心代謝系の定量的モデル2017

    • Author(s)
      松岡結, 倉田博之
    • Organizer
      生命医薬情報学連合大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞工場のコンピュータ支援設計2017

    • Author(s)
      倉田博之
    • Organizer
      化学工学会第49回秋季大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A Large-Scale Dynamic Model of Central Carbon Metabolism for Rational Design of Cell Factories.2017

    • Author(s)
      Hiroyuki Kurata
    • Organizer
      5th International Conference on Biological and Medical Sciences
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] バーチャルメタボリズムの開発と医療への応用2016

    • Author(s)
      倉田 博之
    • Organizer
      化学工学会第48回秋季大会
    • Place of Presentation
      徳島大学 徳島大学
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] Computer Aided Design of Living Systems (CADLIVE)

    • URL

      http://www.cadlive.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] cadlive

    • URL

      http://www.cadlive.jp

    • Related Report
      2017 Annual Research Report
  • [Remarks] CADLIVE

    • URL

      http://www.cadlive.jp

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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