Elucidation of acute toxicity of drugs by real-time metabolome analysis and multivariate time-series analysis
Project/Area Number |
18K10122
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 58040:Forensics medicine-related
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Research Institution | Nagoya University |
Principal Investigator |
Zaitsu Kei 名古屋大学, 医学系研究科, 准教授 (30700546)
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Co-Investigator(Kenkyū-buntansha) |
林 由美 名古屋大学, 医学系研究科(保健), 講師 (30632707)
井口 亮 国立研究開発法人産業技術総合研究所, 地質調査総合センター, 主任研究員 (50547502)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | リアルタイム計測 / 生体医工学 / 脳計測 / 生体分析 / メタボローム解析 / 質量分析 / リアルタイム・メタボローム解析 / バイオインフォマティクス / in vivo リアルタイム計測 / アンビエントイオン化質量分析 / ベイズ統計モデリング / PiTMaP / PESI/MS/MS / Ambient ionization / in vivo リアルタイム・メタボローム解析 / Data pipeline / リアルタイム・メタボローム / メタボロミクス / 法中毒 / リアルタイム・メタボローム分析 / 時系列多変量解析 |
Outline of Final Research Achievements |
In this study, our research team have developed a real-time metabolome analytical technique using probe electrospray ionization tandem mass spectrometry (PESI/MS/MS) with time-series multivariate analyses. We optimized analytical conditions for real-time mass spectrometry, achieving successfully monitoring of 40 metabolites in a living mouse. Our research team has also developed a data pipeline using the R software, and this data pipeline can automatically execute bioinformatics analyses such as multivariate analysis. Moreover, we have developed a new approach using a state space model based on Bayesian statistical modeling for time-series data obtained from real-time monitoring. Finally, we applied this technique to a living mouse, demonstrating the practicality of our technique.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は生体内のメタボロームの変化を生きたマウスから直接検出する手法ならびに時系列データ解析を行う手法を開発したものである。生きたマウスのダイナミクスを直接観察する技術の開発は極めて独自性が高い。さらに、本研究で開発した時系列データ解析は、従来のマイクロダイアリシスなどを用いた細胞外神経伝達物質の挙動を理解するためにも応用可能であるため、学術的にも高い意義を有している。今後、本手法を脳疾患、特に認知症モデルマウスや精神疾患モデルマウスなどに応用することで、従来のアプローチとは異なる知見を得ることができると期待される。
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Metabolome analysisof the serotonin syndrome rat model: abnormal muscular contraction is relatedto metabolic alterations and hyper-thermogenesis2018
Author(s)
Kei Zaitsu*, Saki Noda, Akira Iguchi, Yumi Hayashi, Tomomi Ohara, YuyaKimura, Yuta Koketsu, Tomoko Kosaki, Maiko Kusano, Takako Sato, TetsuyaIshikawa, Hitoshi Tsuchihashi, Koichi Suzuki, Akira Ishii.
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Journal Title
Life Sciences
Volume: 207
Pages: 550-561
DOI
Related Report
Peer Reviewed
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[Presentation] Intact metabolomics by PESI/MS/MS and its application to metabolic profilingof acetaminophen-induced acute hepatic injury model mice2019
Author(s)
Tomomi Ohara,Kenta Kondo, Tasuku Murata, Tetsuya Ishikawa, Akira Ishii, Hitoshi Tsuchihashi,Koretsugu Ogata, Yumi Hayashi, Kei Zaitsu
Organizer
67th ASMS Conferenceon Mass Spectrometry and Allied Topics. (2019/6/5, Atlanta, GA)
Related Report
Int'l Joint Research
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[Presentation] Repeatability and practicality of PESI/MS/MS-based in vivo real-time monitoring system for hepatic/brain metabolites in living mice2019
Author(s)
Kei Zaitsu, Yumi Hayashi, Tasuku Murata, Kazumi Yokota, Tomomi Ohara, Hitoshi Tsuchihashi, Akira Ishii, Koretsugu Ogata, Hiroshi Tanihata
Organizer
67th ASMS Conference on Mass Spectrometry and Allied Topics. (2019/6/6, Atlanta, GA)
Related Report
Int'l Joint Research
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[Presentation] In vivo real-time monitoring system for metabolites in a living mouse brain using probe electrospray ionization/tandem mass spectrometry (PESI/MS/MS).2018
Author(s)
Kei Zaitsu, Yumi Hayashi, Tasuku Murata, Kazumi Yokota, Tomomi Ohara, Maiko Kusano, Tetsuya Ishikawa, Hitoshi Tsuchihashi, Akira Ishii, Koretsugu Ogata, Hiroshi Tanihata.
Organizer
66th ASMS Conference on Mass Spectrometry and Allied Topics
Related Report
Int'l Joint Research
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