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Establishment of autonomous epigenetics analysis for clinical application

Research Project

Project/Area Number 21H03550
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Kaneko Syuzo  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (10777006)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsエピゲノム / オミックス解析 / エピジェネティックス / 自動化 / 機械学習 / ゲノム解析 / 人工知能 / ドライバー遺伝子 / 肺がん / スーパーエンハンサー / 構造多型 / エピジェネティクス / ChIP-seq / Hi-C / ロボティクス
Outline of Research at the Start

エピジェネティクスは遺伝子の機能と環境要因を繋げる分子生物学であり、がん、肥満、アレルギー、統合失調症、またはアルツハイマー病などの原因を理解するために遺伝学と共に重要な概念である。本研究課題ではロボティクス技術を駆使することで実験手法を最適化して、臨床応用や創薬を展開するために必要なデータセットを自動的に取得するシステムを構築する。得られたデータは様々な病態の本態解明に繋がるため、シミュレーションやデータベース検索を駆使した人工知能技術に基づく創薬開発などに応用できることが期待される。

Outline of Final Research Achievements

A prototype of an autonomous epigenetics analysis system utilizing robotics was established. Specifically, the optimization of pretreatment for pathological tissue samples was performed, and ChIP-seq analysis was conducted on over 200 frozen lung cancer tissue samples. The obtained data was processed through an end-to-end pipeline, resulting in high-quality data. Additionally, the combination of three-dimensional genome structure analysis (Hi-C) and whole-genome sequencing elucidated the relationship between epigenetic abnormalities and gene expression. Furthermore, an autonomous machine learning model was constructed, attempting to predict drug targets from sparse Hi-C data.

Academic Significance and Societal Importance of the Research Achievements

学術的には、これらの成果により新たな創薬標的の発見が期待され、エピジェネティクス研究の進展に寄与する。社会的には、このシステムの実用化により、がんをはじめとする様々な疾患の早期診断や個別化医療の実現が加速され、医療の質の向上と患者の生活の質の改善が期待される。

Report

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

    (26 results)

All 2023 2022 2021 Other

All Journal Article (16 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (6 results) Remarks (4 results)

  • [Journal Article] PROX1 induction by autolysosomal activity stabilizes persister-like state of colon cancer via feedback repression of the NOX1-mTORC1 pathway2023

    • Author(s)
      Ohata Hirokazu、Shiokawa Daisuke、Sakai Hiroaki、Kanda Yusuke、Okimoto Yoshie、Kaneko Syuzo、Hamamoto Ryuji、Nakagama Hitoshi、Okamoto Koji
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 6 Pages: 112519-112519

    • DOI

      10.1016/j.celrep.2023.112519

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrative analysis reveals early epigenetic alterations in high-grade serous ovarian carcinomas2023

    • Author(s)
      Machino Hidenori、Dozen Ai、Konaka Mariko、Komatsu Masaaki、Nakamura Kohei、Ikawa Noriko、Shozu Kanto、Asada Ken、Kaneko Syuzo、Yoshida Hiroshi、Kato Tomoyasu、Nakayama Kentaro、Saloura Vassiliki、Kyo Satoru、Hamamoto Ryuji
    • Journal Title

      Experimental & Molecular Medicine

      Volume: 55 Issue: 10 Pages: 2205-2219

    • DOI

      10.1038/s12276-023-01090-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome‐wide association and whole genome sequencing analyses2023

    • Author(s)
      Shiraishi Kouya、Takahashi Atsushi、、et al.
    • Journal Title

      Cancer Communications

      Volume: 44 Issue: 2 Pages: 287-293

    • DOI

      10.1002/cac2.12498

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Advances in cancer DNA methylation analysis with methPLIER: use of non-negative matrix factorization and knowledge-based constraints to enhance biological interpretability2023

    • Author(s)
      Takasawa K, Asada K, Kaneko S, Shiraishi K, Machino H, Takahashi S, Shinkai N, Kouno N, Kobayashi K, Komatsu M, Mizuno T, Okubo Y, Mukai M, Yoshida T, Yoshida Y, Horinouchi H, Watanabe S, Ohe Y, Yatabe Y, Kohno T, Hamamoto R
    • Journal Title

      Experimental and Molecular Medicine

      Volume: 56 Issue: 3 Pages: 646-655

    • DOI

      10.1038/s12276-024-01173-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of super-enhancer using machine learning and its application to medical biology2023

    • Author(s)
      Hamamoto Ryuji、Takasawa Ken、Shinkai Norio、Machino Hidenori、Kouno Nobuji、Asada Ken、Komatsu Masaaki、Kaneko Syuzo
    • Journal Title

      Briefings in Bioinformatics

      Volume: - Issue: 3

    • DOI

      10.1093/bib/bbad107

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Appkication of non-negative matrix fractorization in oncology: one approach for establishing precision medicine2022

    • Author(s)
      Hamamoto R, Takasawa K, Machino H, Kobayashi K, Takahashi S, Bolatkan A, Shinkai N, Sakai A, Aoyama R, Yamada M, Asada K, Komatsu M, Okamoto K, Kameoka H, Kaneko S
    • Journal Title

      Briefings in Bioinformatics

      Volume: 23 Issue: 4

    • DOI

      10.1093/bib/bbac246

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Introducing AI to the molecular tumor board: one direction toward the establishment of precision medicine using large-scale cancer clinical and biological information2022

    • Author(s)
      Hamamoto R, Koyama T, Kouno N, Yasuda T, Yui S, Sudo K, Hirata M, Sunami K, Kubo T, Takasawa K, Takahashi S, Machino H, Kobayashi K, Asada K, Komatsu M, Kaneko S, Yatabe Y, Yamamoto N
    • Journal Title

      Experimental Biology and Oncology

      Volume: 11 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s40164-022-00333-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells2022

    • Author(s)
      Kukita Asako、Sone Kenbun、Wada-Hiraike Osamu (21)、Oda Katsutoshi、Hamamoto Ryuji、Osuga Yutaka
    • Journal Title

      Cancers

      Volume: 14 Issue: 21 Pages: 5367-5367

    • DOI

      10.3390/cancers14215367

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer2022

    • Author(s)
      Shozu Kanto、Kaneko Syuzo、Shinkai Norio、Dozen Ai、Kosuge Hirofumi、Nakakido Makoto、Machino Hidenori、Takasawa Ken、Asada Ken、Komatsu Masaaki、Tsumoto Kouhei、Ohnuma Shin-Ichi、Hamamoto Ryuji
    • Journal Title

      Clinical Epigenetics

      Volume: 14 Issue: 1 Pages: 1-13

    • DOI

      10.1186/s13148-022-01370-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma2022

    • Author(s)
      Dozen Ai、Shozu Kanto、Shinkai Norio、Ikawa Noriko、Aoyama Rina、Machino Hidenori、Asada Ken、Yoshida Hiroshi、Kato Tomoyasu、Hamamoto Ryuji、Kaneko Syuzo、Komatsu Masaaki
    • Journal Title

      Journal of Personalized Medicine

      Volume: 12 Issue: 12 Pages: 1999-1999

    • DOI

      10.3390/jpm12121999

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma2022

    • Author(s)
      Hidenori Machino, Syuzo Kaneko, Masaaki Komatsu, Noriko Ikawa, Ken Asada, Ryuichiro Nakato, Kanto Shozu, Ai Dozen, Kenbun Sone, Hiroshi Yoshida, Tomoyasu Kato, Katsutoshi Oda, Yutaka Osuga, Tomoyuki Fujii, Gottfried von Keudell, Vassiliki Saloura, Ryuji Hamamoto
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 39-39

    • DOI

      10.1038/s42003-021-02992-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules2021

    • Author(s)
      Bolatkan Amina、Asada Ken、Kaneko Syuzo、Suvarna Kruthi、Ikawa Noriko、Machino Hidenori、Komatsu Masaaki、Shiina Shuichiro、Hamamoto Ryuji
    • Journal Title

      International Journal of Oncology

      Volume: 60 Issue: 1 Pages: 4-4

    • DOI

      10.3892/ijo.2021.5294

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell analysis using machine learning techniques and its application to medical research2021

    • Author(s)
      Asada Ken、Takasawa Ken、Machino Hidenori、Takahashi Satoshi、Shinkai Norio、Bolatkan Amina、Kobayashi Kazuma、Komatsu Masaaki、Kaneko Syuzo、Okamoto Koji、Hamamoto Ryuji
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 11 Pages: 1513-1513

    • DOI

      10.3390/biomedicines9111513

    • URL

      https://pure.teikyo.jp/en/publications/62c16c6c-90f4-46ba-86ad-f5824a5f1ce4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Artificial Intelligence in COVID-19 Diagnosis and Therapeutics2021

    • Author(s)
      Asada Ken、Komatsu Masaaki、Shimoyama Ryo、Takasawa Ken、Shinkai Norio、Sakai Akira、Bolatkan Amina、Yamada Masayoshi、Takahashi Satoshi、Machino Hidenori、Kobayashi Kazuma、Kaneko Syuzo、Hamamoto Ryuji
    • Journal Title

      Journal of Personalized Medicine

      Volume: 11 Issue: 9 Pages: 886-886

    • DOI

      10.3390/jpm11090886

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic Mechanisms Underlying COVID-19 Pathogenesis2021

    • Author(s)
      Kaneko Syuzo、Takasawa Ken、Asada Ken、Shinkai Norio、Bolatkan Amina、Yamada Masayoshi、Takahashi Satoshi、Machino Hidenori、Kobayashi Kazuma、Komatsu Masaaki、Hamamoto Ryuji
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 9 Pages: 1142-1142

    • DOI

      10.3390/biomedicines9091142

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated Analysis of Whole Genome and Epigenome Data Using Machine Learning Technology: Toward the Establishment of Precision Oncology2021

    • Author(s)
      Ken Asada, Syuzo Kaneko, Ken Takasawa, Hidenori Machino, Satoshi Takahashi, Norio Shinkai, Ryo Shimoyama, Masaaki Komatsu, Ryuji Hamamoto
    • Journal Title

      Frontiers in Oncology

      Volume: 11 Pages: 666937-666937

    • DOI

      10.3389/fonc.2021.666937

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲノムコピー数異常を指標とした創薬標的予測モデルの構築2023

    • Author(s)
      金子修三、浜本隆二
    • Organizer
      第5回日本メディカルAI学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ゲノムコピー数異常を指標とした創薬標的予測モデルの構築に向けた試み2023

    • Author(s)
      金子修三、浜本隆二
    • Organizer
      第82回 日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Emerging approaches to the identification of driver mutations in lung cancer2022

    • Author(s)
      Syuzo Kaneko and Ryuji Hamamoto
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Integrated analysis of ChIP-seq and whole-genome sequencing in lung cancer2022

    • Author(s)
      Syuzo Kaneko and Ryuji Hamamoto
    • Organizer
      第4回日本メディカルAI学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Large-scale lung cancer ChIP-seq analysis using robots2021

    • Author(s)
      Syuzo Kaneko and Ryuji Hamamoto
    • Organizer
      日本メディカルAI学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Large-scale ChIP-seq analysis in pan-negative lung cancer2021

    • Author(s)
      Syuzo Kaneko and Ryuji Hamamoto
    • Organizer
      日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 2023年研究論文刊行成果

    • URL

      https://www.ncc.go.jp/jp/ri/division/molecular_modification_and_cancer_biology/paper/132/20230418184713.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] 医療AI研究開発分野 研究室の紹介

    • URL

      https://www.ncc.go.jp/jp/ri/division/molecular_modification_and_cancer_biology/index.html

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report
  • [Remarks] 2022年研究論文刊行成果

    • URL

      https://www.ncc.go.jp/jp/ri/division/molecular_modification_and_cancer_biology/paper/131/20170908150849.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 2021年研究論文刊行成果

    • URL

      https://www.ncc.go.jp/jp/ri/division/molecular_modification_and_cancer_biology/paper/130/20170908150849.html

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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