Development of next-generation trans-omics technologies for multi-timescale metabolic regulation in psychiatric disorders

• Project Area: Constructive understanding of multi-scale dynamism of neuropsychiatric disorders
• Project/Area Number: 18H05431
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Yugi Katsuyuki 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (70433745)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000); Fiscal Year 2022: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2021: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2020: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000); Fiscal Year 2019: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000); Fiscal Year 2018: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: トランスオミクス / 代謝 / システム生物学 / 神経科学 / 多階層ネットワーク / 精神疾患 / 数理モデル

Outline of Final Research Achievements

We have developed a 'trans-omic' data integration technologies that allows elucidating the molecular basis of psychiatric disorders as multi-layered molecular networks. These technologies enable data integration of multiple omics data in vivo (Kokaji et al. 2020, Science Signaling) and public omics data (Okamoto et al. 2022, Neuroscience Research). Furthermore, trans-omics analysis is now applicable to steady-state (one data point) omics data (Egami et al. 2021, iScience), whereas previous framework required time-series omics data.

Academic Significance and Societal Importance of the Research Achievements

従来のトランスオミクス解析の応用範囲は代謝などの「速い」分子基盤を持つ生命現象に限定されていた。本研究成果により、遺伝子発現関連の比較的「遅い」オミクス階層を取り扱えるようになったほか、データ点数の少ないオミクスデータや公共データも利用可能になった。これにより、本領域のテーマである精神疾患をはじめとする多様な生命現象や疾患の分子基盤解明に対してトランスオミクス解析を適用することが可能になった。

Research Products

• [Int'l Joint Research] Harvard Medical School(米国)
• [Int'l Joint Research] シドニー大学(オーストラリア)
• [Int'l Joint Research] シドニー大学(オーストラリア)
• [Int'l Joint Research] シドニー大学(オーストラリア)
• [Journal Article] In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states. (2022)
  • Author(s): Kokaji T, Eto M, Hatano A, Yugi K, Morita K, Ohno S, Fujii M, Hironaka KI, Ito Y, Egami R, Uematsu S, Terakawa A, Pan Y, Maehara H, Li D, Bai Y, Tsuchiya T, Ozaki H, Inoue H, Kubota H, Suzuki Y, Hirayama A, Soga T, Kuroda S.
  • Journal Title: Sci Rep Volume: 12 Issue: 1 Pages: 13719-13719
  • DOI: 10.1038/s41598-022-17964-9
  • Peer Reviewed / Open Access
• [Journal Article] Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes (2022)
  • Author(s): Terakawa Akira、Hu Yanhui、Kokaji Toshiya、Yugi Katsuyuki、Morita Keigo、Ohno Satoshi、Pan Yifei、Bai Yunfan、Parkhitko Andrey A.、Ni Xiaochun、Asara John M.、Bulyk Martha L.、Perrimon Norbert、Kuroda Shinya
  • Journal Title: iScience Volume: 25 Issue: 5 Pages: 104231-104231
  • DOI: 10.1016/j.isci.2022.104231
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach (2022)
  • Author(s): Okamoto Lisa、Watanabe Soyoka、Deno Senka、Nie Xiang、Maruyama Junichi、Tomita Masaru、Hatano Atsushi、Yugi Katsuyuki
  • Journal Title: Neuroscience Research Volume: 175 Pages: 82-97
  • DOI: 10.1016/j.neures.2021.12.006
  • Peer Reviewed / Open Access
• [Journal Article] Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle (2021)
  • Author(s): Egami Riku、Kokaji Toshiya、Hatano Atsushi、et al.
  • Journal Title: iScience Volume: 24 Issue: 3 Pages: 102217-102217
  • DOI: 10.1016/j.isci.2021.102217
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 複数のオミクス階層にまたがる大規模パスウェイの2.5次元可視化 (2021)
  • Author(s): 西田孝三, 高橋恒一, 柚木克之
  • Journal Title: 実験医学別冊 メタボロミクス実践ガイド Volume: - Pages: 237-251
• [Journal Article] 生活習慣病のトランスオミクス解析 (2021)
  • Author(s): 柚木克之, 小鍛治俊也, 角田達彦, 黒田真也
  • Journal Title: 医学のあゆみ Volume: 278 Pages: 501-509
• [Journal Article] Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity (2020)
  • Author(s): Kokaji Toshiya、Hatano Atsushi、Ito Yuki、et al.
  • Journal Title: Science Signaling Volume: 13 Issue: 660 Pages: 1236-1236
  • DOI: 10.1126/scisignal.aaz1236
  • Peer Reviewed / Open Access
• [Journal Article] Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes (2020)
  • Author(s): Hoshino Daisuke、Kawata Kentaro、Kunida Katsuyuki、Hatano Atsushi、Yugi Katsuyuki、Wada Takumi、Fujii Masashi、Sano Takanori、Ito Yuki、Furuichi Yasuro、Manabe Yasuko、Suzuki Yutaka、Fujii Nobuharu L.、Soga Tomoyoshi、Kuroda Shinya
  • Journal Title: iScience Volume: 23 Issue: 10 Pages: 101558-101558
  • DOI: 10.1016/j.isci.2020.101558
  • Peer Reviewed / Open Access
• [Journal Article] Kinetic Trans-omic Analysis Reveals Key Regulatory Mechanisms for Insulin-Regulated Glucose Metabolism in Adipocytes (2020)
  • Author(s): Ohno Satoshi、Quek Lake-Ee、Krycer James R.、Yugi Katsuyuki、Hirayama Akiyoshi、Ikeda Satsuki、Shoji Futaba、Suzuki Kumi、Soga Tomoyoshi、James David E.、Kuroda Shinya
  • Journal Title: iScience Volume: 23 Issue: 9 Pages: 101479-101479
  • DOI: 10.1016/j.isci.2020.101479
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rate-oriented trans-omics: integration of multiple omic data on the basis of reaction kinetics (2019)
  • Author(s): Yugi Katsuyuki、Ohno Satoshi、Krycer James R.、James David E.、Kuroda Shinya
  • Journal Title: Current Opinion in Systems Biology Volume: 15 Pages: 109-120
  • DOI: 10.1016/j.coisb.2019.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] トランスオミクスの考え方と実験デザイン (2019)
  • Author(s): 柚木克之
  • Journal Title: 細胞 Volume: 51 Pages: 701-705
• [Journal Article] トランスオミクス・統合オミクス研究による免疫代謝・腸内細菌代謝研究 (2019)
  • Author(s): 出野泉花, 柚木克之
  • Journal Title: 臨床免疫・アレルギー科 Volume: 72 Pages: 342-350
• [Journal Article] Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data (2018)
  • Author(s): Kawata Kentaro、Yugi Katsuyuki、Hatano Atsushi、Kokaji Toshiya、Tomizawa Yoko、Fujii Masashi、Uda Shinsuke、Kubota Hiroyuki、Matsumoto Masaki、Nakayama Keiichi I.、Kuroda Shinya
  • Journal Title: Genes to Cells Volume: 24 Issue: 1 Pages: 82-93
  • DOI: 10.1111/gtc.12655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 細胞の反応速度論的描像に基づく統合オミクス解析 (2020)
  • Author(s): 柚木克之
  • Organizer: 日本バイオインフォマティクス学会年会
• [Presentation] Reconstruction of insulin signal flow from phosphoproteome and metabolome data (2020)
  • Author(s): Yugi K.
  • Organizer: KI-RIKEN Joint International Doctoral Course 2020
  • Int'l Joint Research / Invited
• [Presentation] トランスオミクス解析によるインスリン代謝制御ネットワークの再構築 (2019)
  • Author(s): 柚木克之
  • Organizer: 第92回日本内分泌学会学術総会
  • Invited
• [Presentation] Integration of phosphoproteome and 13C-metabolome data reveals ‘metabolic priming’ in the adipocyte (2019)
  • Author(s): Yugi, K.
  • Organizer: 3rd RIKEN IMS-Stanford ISCBRM Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] トランスオミクス研究の現在地および免疫代謝研究への展望 (2019)
  • Author(s): 柚木克之
  • Organizer: 第7回がんと代謝研究会
  • Invited
• [Presentation] 多階層オミクスデータ解析の自動化に向けて (2019)
  • Author(s): 柚木克之
  • Organizer: 第44回日本医用マススペクトル学会
• [Presentation] 3 つのオミクス階層を縦断するインスリン濃度選択的制御軸の発見 (2019)
  • Author(s): 柚木克之
  • Organizer: 第13回メタボロームシンポジウム
• [Presentation] Dose-selective metabolic regulation by insulin across multiple omic layers (2019)
  • Author(s): Yugi, K.
  • Organizer: The 3rd International Symposium for TransOmics
  • Int'l Joint Research / Invited
• [Presentation] Trans-omics: integration of multiple omic data on the basis of reaction kinetic (2019)
  • Author(s): Yugi, K.
  • Organizer: The 6th RIKEN-KI-SciLifeLab Symposium: Biomedical Data for Artificial Intelligence
  • Int'l Joint Research / Invited
• [Presentation] Trans-omics: integration of multiple omic data on the basis of reaction kinetics (2019)
  • Author(s): Yugi, K.
  • Organizer: The 4th Symposium of Inter-University Research Network for Trans-Omics Medicine
  • Int'l Joint Research / Invited
• [Presentation] Dose-selective metabolic regulation by insulin across multiple omic layers (2019)
  • Author(s): Yugi, K.
  • Organizer: RIKEN-KU Leuven Joint Symposium 2019
  • Int'l Joint Research / Invited
• [Presentation] トランスオミクス：細胞の反応速度論的描像に基づく統合オミクス解析 (2019)
  • Author(s): 柚木克之
  • Organizer: 第412回CBI学会講演会
  • Invited
• [Remarks] インスリン刺激下で細胞増殖を促進する分子間相互作用ネットワークを生体分子の大規模計測データから解明
  • URL: https://www.s.u-tokyo.ac.jp/ja/press/2022/7841/