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Development of deep phenotyping method that enables analysis and application of latent drug response

Research Project

Project/Area Number 17K19478
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kusuhara Hiroyuki  東京大学, 大学院薬学系研究科(薬学部), 教授 (00302612)

Research Collaborator Mizuno Tadahaya  , 助教
Kinoshita Setsuo  , 受託研究員
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsプロファイリング / OLSA / トランスクリプトームデータ / プロテオームデータ / 抗がん剤 / 併用効果 / 2次元電気泳動 / オミクスデータ / トランスクリプトーム / プロファイルデータ / 薬剤応答 / プロファイル / 二次元電気泳動
Outline of Final Research Achievements

This study was designed to demonstrate that the new profile data analysis method, OLSA, and the profile data acquisition methodology, two-dimensional electrophoresis using mini-gel, help "deep" understanding of drug action. OLSA achieved extraction of mathematical structures with biological meanings even based on transcriptome data. In data acquisition by two-dimensional electrophoresis, we also overcome problems such as variability between experiments. This study achieved a clear classification for each drug's action using OLSA. As a result of exposure to anticancer drugs, common effects that are considered to be cell death, effects to be canceled by combination, and effects that are considered to be new ones by combination are extracted. We considered that the analysis elucidated drug single and combined effects of anti-cancer drugs.

Academic Significance and Societal Importance of the Research Achievements

当初の期待通り,OLSAを利用することで,トランスクリプトーム・プロテオームいずれのオミクスデータからも研究者が必ずしも定義していない(できていない)表現型をも利用して、薬物応答性を体系的に捉えることを支援し、薬物応答を深く理解できることを実証した。単剤のみではなく,併用による作用も検出できたことから,有効な抗がん剤の組み合わせを解明することにも貢献するものである。さらに,薬物に限らず,刺激に対する細胞および生体の応答性解析という観点から適用範囲は非常に広く、薬物動態領域にかかわらず、他の研究領域においても有用な実験ツールとして波及効果も期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Development of Orthogonal Linear Separation Analysis (OLSA) to Decompose Drug Effects into Basic Components.2019

    • Author(s)
      Mizuno T, Kinoshita S, Ito T, Maedera S, Kusuhara H.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 1824-1824

    • DOI

      10.1038/s41598-019-38528-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of Orthogonal Linear Separation Analysis (OLSA) to Decompose Pharmacological Effect and Extract Elementary Ones2019

    • Author(s)
      Hiroyuki Kusuhara
    • Organizer
      第13回杉山特別研究室(理研)公開シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 生物応答の解析方法、解析プログラム、及び解析装置2018

    • Inventor(s)
      楠原洋之,水野忠快, 木之下節夫,佐竹和子
    • Industrial Property Rights Holder
      楠原洋之,水野忠快, 木之下節夫,佐竹和子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-042467
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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