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Development of fundamental technologies for data-driven optimisation of cell culture

Research Project

Project/Area Number 21K19815
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 62:Applied informatics and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

YING Bei-Wen  筑波大学, 生命環境系, 准教授 (90422401)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords細胞培養 / 機械学習 / 培地 / データサイエンス / ビッグデータ / 細胞増殖 / 増殖速度
Outline of Research at the Start

本研究は経験則で行われている細胞培養に応用情報科学的研究手法を取り入れることにより、細胞の振る舞いに対する高度な制御に繋げ、細胞培養の諸問題を解決する。具体的には、網羅的実験により、培地成分と培養の良し悪しが繋ぐビッグデータを蓄積し、世界初となる「環境情報-細胞動態」のデータベースを構築する。実験データに機械学習を適用し、どの環境因子がどの程度に細胞増殖(培養)に寄与するのかを予測し、それらの相対重要度を明らかにする。実験と学習の繰り返しにより、予測精度を向上させ、目的に応じた細胞培養の合理化や至適化を実現する。

Outline of Final Research Achievements

This study was to address issues pertaining to the reproducibility and productivity of cell culture. A data science approach was employed to improve cell culture, which is commonly based on individual senses. Through a series of comprehensive experiments, a substantial amount of data was gathered, linking specific culture conditions with the resulting quality of the culture. The dataset was then used to construct the database of ‘environmental information- cell growth’. Machine learning was applied to the experimental data in order to predict which environmental factors contribute to cell culture and to what extent, as well as to identify their relative importance. Active learning (repeated experiments and learning) was employed to enhance the prediction accuracy of the learning model and optimise the culture medium for cell culture.The culture experiments and machine learning methods established in this study can be applied to a variety of cell cultures.

Academic Significance and Societal Importance of the Research Achievements

細胞培養は基礎研究においても、健康と医療のための産業応用においても、普遍的技術であるにも拘わらず、細胞培養の再現性、安定性、安全性の課題が長年に渡って未解決のままである。本研究はアナログ方式で行われている細胞培養に、デジタル方式である応用情報科学的研究手法を取り入れることにより、細胞増殖に対する高度な制御を実現し、細胞培養の諸問題を解決することに繋がる。本研究は、機械学習・人工知能が職人芸的な細胞培養にある根幹問題を解決する初めての挑戦であり、その成功が生命科学研究において抜本的なトレンドチェンジとなる。本研究で検証される方法論が細胞培養の不確実性を減らし、再生医療の産業化に寄与する。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (33 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Open Access: 10 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Challenges in developing cell culture media using machine learning2024

    • Author(s)
      Hashizume Takamasa、Ying Bei-Wen
    • Journal Title

      Biotechnology Advances

      Volume: 70 Pages: 108293-108293

    • DOI

      10.1016/j.biotechadv.2023.108293

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Machine learning-assisted medium optimization revealed the discriminated strategies for improved production of the foreign and native metabolites2023

    • Author(s)
      Aida Honoka、Uchida Keisuke、Nagai Motoki、Hashizume Takamasa、Masuo Shunsuke、Takaya Naoki、Ying Bei-Wen
    • Journal Title

      Computational and Structural Biotechnology Journal

      Volume: 21 Pages: 2654-2663

    • DOI

      10.1016/j.csbj.2023.04.020

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diversity for commonality in the evolutionary changes of the reduced genome to regain the growth fitness2023

    • Author(s)
      Hitomi Kenya、Ishii Yoichiro、Ying Bei-Wen
    • Journal Title

      eLife

      Volume: 12 Pages: 93520-93520

    • DOI

      10.7554/elife.93520.1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efforts to Minimise the Bacterial Genome as a Free-Living Growing System2023

    • Author(s)
      Aida Honoka、Ying Bei-Wen
    • Journal Title

      Biology

      Volume: 12 Issue: 9 Pages: 1170-1170

    • DOI

      10.3390/biology12091170

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Employing Active Learning in Medium Optimization for Selective Bacterial Growth2023

    • Author(s)
      Zhang Shuyang、Aida Honoka、Ying Bei-Wen
    • Journal Title

      Applied Microbiology

      Volume: 3 Issue: 4 Pages: 1355-1369

    • DOI

      10.3390/applmicrobiol3040091

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Employing active learning in the optimization of culture medium for mammalian cells2023

    • Author(s)
      Hashizume Takamasa、Ozawa Yuki、Ying Bei-Wen
    • Journal Title

      npj Systems Biology and Applications

      Volume: 9 Issue: 1 Pages: 20-20

    • DOI

      10.1038/s41540-023-00284-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity.2023

    • Author(s)
      H Aida, K Uchida, M Nagai, T Hashizume, S Masuo, N Takaya, BW Ying
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.12.24.521878

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity.2022

    • Author(s)
      H Aida, T Hashizume, K Ashino, BW Ying
    • Journal Title

      eLife

      Volume: 11

    • DOI

      10.7554/elife.76846

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the genomic and nutritional differentiation to the spatial distribution of bacterial colonies.2022

    • Author(s)
      K Hitomi, J Weng, BW Ying
    • Journal Title

      Front Microbial

      Volume: 13

    • DOI

      10.3389/fmicb.2022.948657

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experimental evolution expands the breadth of adaptation to an environmental gradient correlated with genome reduction.2022

    • Author(s)
      M Kurokawa, I Nishimura, BW Ying
    • Journal Title

      Front Microbial

      Volume: 13

    • DOI

      10.3389/fmicb.2022.826894

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Machine learning-assisted discovery of growth decision elements by relating bacterial population dynamics to environmental diversity.2022

    • Author(s)
      AIDA honoka; HASHIZUME Takamasa; ASHINO Kazuha; YING BEIWEN
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.02.10.479953

    • Related Report
      2021 Research-status Report
    • Open Access
  • [Presentation] 細菌の多剤耐性に影響を与える化学成分の網羅的探索2024

    • Author(s)
      荒木 駿平; 會田 穂乃香; イン ベイウェン
    • Organizer
      日本農芸化学会2024年度東京大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 機械学習による微生物の選択的増殖の培地開発2024

    • Author(s)
      張 抒楊; 會田 穂乃香; イン ベイウェン
    • Organizer
      日本農芸化学会2024年度東京大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌の増殖を特徴づける化学成分の機械学習支援型探索2024

    • Author(s)
      會田 穂乃香; イン ベイウェン
    • Organizer
      日本農芸化学会2024年度東京大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Compensation of medium composition to genome reduction2023

    • Author(s)
      LU Zipeng; YING Bei-Wen
    • Organizer
      日本ゲノム微生物学会第18回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 大腸菌増殖を特徴づける遺伝的要件と化学環境の横断的探索2023

    • Author(s)
      會田 穂乃香; イン ベイウェン
    • Organizer
      日本ゲノム微生物学会第18回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A preliminary analysis of the growth curves of bacterial strains knocked out by a single gene2023

    • Author(s)
      LAO Zehui; YING Bei-Wen
    • Organizer
      日本ゲノム微生物学会第18回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Time-saving medium development for improved cell culture2023

    • Author(s)
      OZAWA Yuki; HASHIZUME Takamasa; YING Bei-Wen
    • Organizer
      JAACT2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Medium optimization for mammalian cells using machine learning2023

    • Author(s)
      HASHIZUME Takamasa; OZAWA Yuki; YING Bei-Wen
    • Organizer
      JAACT2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Machine learning-assisted discovery of the bacterial growth strategy of risk diversification2023

    • Author(s)
      AIDA Honoka; YING Bei-Wen
    • Organizer
      Tsukuba Conference 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Active learning optimization of culture medium for mammalian cells2023

    • Author(s)
      HASHIZUME Takamasa; YING Bei-Wen
    • Organizer
      Tsukuba Conference 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機械学習による微生物選択培地の最適化2023

    • Author(s)
      張抒楊、會田穂乃香、イン ベイウェン
    • Organizer
      日本農芸化学会2023年度広島大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 遺伝情報と化学環境が大腸菌増殖に与える影響の横断的探索2023

    • Author(s)
      會田穂乃香、イン ベイウェン
    • Organizer
      日本ゲノム微生物学会第17回大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 細菌の増殖動態を決定する環境因子の機械学習支援型探索2023

    • Author(s)
      會田穂乃香、イン ベイウェン
    • Organizer
      日本農芸化学会2023年度広島大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 細胞培養のデータ駆動式培地開発2022

    • Author(s)
      橋詰崇雅、イン ベイウェン
    • Organizer
      日本動物細胞工学会JAACT2022
    • Related Report
      2022 Research-status Report
  • [Presentation] バイオマス生産最適化に向けたデータ駆動型システム微生物2022

    • Author(s)
      イン ベイウェン
    • Organizer
      MiCSワークショップ
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 機械学習による細胞増殖の予測とその制御2022

    • Author(s)
      イン ベイウェン
    • Organizer
      技術情報協会公開セミナー
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 機械学習による微生物増殖の予測2022

    • Author(s)
      橋詰 崇雅、會田 穂乃香、イン ベイウェン
    • Organizer
      日本ゲノム微生物学会第16回大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大腸菌増殖を決定する環境因子の網羅的探索2022

    • Author(s)
      會田 穂乃香、橋詰 崇雅、イン ベイウェン
    • Organizer
      日本ゲノム微生物学会第16回大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 微生物集団増殖に優位的に影響する環境因子の探索2021

    • Author(s)
      會田 穂乃香、橋詰 崇雅、イン ベイウェン
    • Organizer
      日本微生物生態学会第34回大会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 培養環境判定システム、培養装置、要求取得装置及びプログラム2022

    • Inventor(s)
      イン ベイウェン、會田 穂乃香、橋詰 崇雅
    • Industrial Property Rights Holder
      イン ベイウェン、會田 穂乃香、橋詰 崇雅
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 培養環境判定装置、培養システム、培養環境判定方法、培養方法、及びプログラム2022

    • Inventor(s)
      イン ベイウェン、天笠 俊之
    • Industrial Property Rights Holder
      イン ベイウェン、天笠 俊之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 微生物培養用合成培地及び微生物の培養方法2021

    • Inventor(s)
      イン ベイウェン、會田 穂乃香
    • Industrial Property Rights Holder
      イン ベイウェン、會田 穂乃香
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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