Illuminating new biological mechanisms by multiomics approach with mass spectrometry cheminformatics

• Project/Area Number: 18H02432
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Tokyo University of Agriculture and Technology (2020-2021); Institute of Physical and Chemical Research (2018-2019)
• Principal Investigator: Tsugawa Hiroshi 東京農工大学, 工学(系)研究科(研究院), 准教授 (30647235)
• Co-Investigator(Kenkyū-buntansha): 中林 亮 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (30586160)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: システムバイオロジー / オミクス科学 / 質量分析 / インフォマティクス / メタボロミクス / リピドミクス / 統合オミクス / 質量分析インフォマティクス / データサイエンス / メタボローム / 植物特異的代謝物 / 二次代謝物 / SNPs / メタボローム解析 / 化合物同定 / マルチオミクス

Outline of Final Research Achievements

The researcher is engaged in informatics research to analyze the mass spectrometry data for extracting metabolite information. By using our computational mass spectrometry technique, we conduct integrated omics research based on the identification of novel metabolites and metabolome networks. The results include the development of novel metabolomics technique (FSEA method) for elucidating plant-specific natural products and the integrated omics approach of single nucleotide polymorphism (SNP) data with the metabolome in Arabidopsis thaliana (Nature Methods 2019). In addition, the innovative method for lipid metabolomics (lipidomics) to reveal the lipid diversity of living organisms has been developed (Nature Biotechnology 2020).

Academic Significance and Societal Importance of the Research Achievements

生命活動の中枢である「代謝」を理解することは、喫緊の課題である環境問題を微生物の力で解決することや、感染防御の分子メカニズムの解明することによる新たな創薬研究に繋がる。一方、生命の細胞内での産生や分解過程を通じてできる「代謝物（メタボローム）」は100万種類を超えると言われており、その多様性を捉える技術を作ることが代謝の理解に直結すると言える。本研究で構築された革新的なメタボローム解析技術により、これまでよりも１０倍以上の網羅性を担保した代謝物解析が可能となったことに加え、遺伝子発現データとの統合解析により、代謝物の生理学的意義を明らかにする方法論も構築した。

Research Products

• [Int'l Joint Research] Wageningen University & Research(オランダ)
• [Int'l Joint Research] Czech Academy of Sciences(チェコ)
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] UC Davis(米国)
• [Journal Article] Global profiling of gut microbiota-associated lipid metabolites in antibiotic-treated mice by LC-MS/MS-based analyses (2021)
  • Author(s): Okahashi Nobuyuki、Ueda Masahiro、Yasuda Shu、Tsugawa Hiroshi、Arita Makoto
  • Journal Title: STAR Protocols Volume: 2 Issue: 2 Pages: 100492-100492
  • DOI: 10.1016/j.xpro.2021.100492
  • Peer Reviewed / Open Access
• [Journal Article] Stage-specific de novo synthesis of very long chain dihydroceramides confers dormancy to Entamoeba parasites (2021)
  • Author(s): Fumika Mi-ichi Kazutaka Ikeda Hiroshi Tsugawa Sharmina Deloer Hiroki Yoshida Makoto Arita
  • Journal Title: mSphere Volume: 6 Issue: 2 Pages: 00174-21
  • DOI: 10.1128/msphere.00174-21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Food Lipidomics for 155 Agricultural Plant Products (2021)
  • Author(s): Matsuzawa Yuki、Higashi Yasuhiro、Takano Kouji、Takahashi Mikiko、Yamada Yutaka、Okazaki Yozo、Nakabayashi Ryo、Saito Kazuki、Tsugawa Hiroshi
  • Journal Title: Journal of Agricultural and Food Chemistry Volume: 69 Issue: 32 Pages: 8981-8990
  • DOI: 10.1021/acs.jafc.0c07356
  • Peer Reviewed
• [Journal Article] Metabolomics and complementary techniques to investigate the plant phytochemical cosmos (2021)
  • Author(s): Tsugawa Hiroshi、Rai Amit、Saito Kazuki、Nakabayashi Ryo
  • Journal Title: Natural Product Reports Volume: 38 Issue: 10 Pages: 1729-1759
  • DOI: 10.1039/d1np00014d
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolomics with 15N Labeling for Characterizing Missing Monoterpene Indole Alkaloids in Plants (2020)
  • Author(s): Nakabayashi Ryo、Mori Tetsuya、Takeda Noriko、Toyooka Kiminori、Sudo Hiroshi、Tsugawa Hiroshi、Saito Kazuki
  • Journal Title: Analytical Chemistry Volume: 92 Issue: 8 Pages: 5670-5675
  • DOI: 10.1021/acs.analchem.9b03860
  • Peer Reviewed / Open Access
• [Journal Article] Creating a Reliable Mass Spectral-Retention Time Library for All Ion Fragmentation-Based Metabolomics (2019)
  • Author(s): Tada Ipputa、Tsugawa Hiroshi、Meister Isabel、Zhang Pei、Shu Rie、Katsumi Riho、Wheelock Craig E.、Arita Masanori、Chaleckis Romanas
  • Journal Title: Metabolites Volume: 9 Issue: 11 Pages: 251-251
  • DOI: 10.3390/metabo9110251
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of Lipid Profiles after Dietary Intake of Polyunsaturated Fatty Acids Using Integrated Untargeted and Targeted Lipidomics (2019)
  • Author(s): Naoe Satoko、Tsugawa Hiroshi、Takahashi Mikiko、Ikeda Kazutaka、Arita Makoto
  • Journal Title: Metabolites Volume: 9 Issue: 10 Pages: 241-241
  • DOI: 10.3390/metabo9100241
  • Peer Reviewed / Open Access
• [Journal Article] Mass Spectrometry Data Repository Enhances Novel Metabolite Discoveries with Advances in Computational Metabolomics (2019)
  • Author(s): Tsugawa Hiroshi、Satoh Aya、Uchino Haruki、Cajka Tomas、Arita Makoto、Arita Masanori
  • Journal Title: Metabolites Volume: 9 Issue: 6 Pages: 119-119
  • DOI: 10.3390/metabo9060119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A cheminformatics approach to characterize metabolomes in stable-isotope-labeled organisms (2019)
  • Author(s): Tsugawa Hiroshi、Nakabayashi Ryo、Mori Tetsuya、Yamada Yutaka、Takahashi Mikiko、Rai Amit、Sugiyama Ryosuke、Yamamoto Hiroyuki、Nakaya Taiki、Yamazaki Mami、Kooke Rik、Bac-Molenaar Johanna A.、Oztolan-Erol Nihal、Keurentjes Joost J. B.、Arita Masanori、Saito Kazuki
  • Journal Title: Nature Methods Volume: 16 Issue: 4 Pages: 295-298
  • DOI: 10.1038/s41592-019-0358-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Advances in computational metabolomics and databases deepen the understanding of metabolisms (2018)
  • Author(s): Hiroshi Tsugawa
  • Journal Title: Current Opinion in Biotechnology Volume: 54 Pages: 10-17
  • DOI: 10.1016/j.copbio.2018.01.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics (2017)
  • Author(s): Lai Z, Tsugawa H, Wohlgemuth G, Mehta S, Mueller M, Zheng Y, Ogiwara A, Meissen J, Showalter M, Takeuchi K, Kind T, Beal P, Arita M, Fiehn O
  • Journal Title: Nature Methods Volume: 15 Issue: 1 Pages: 53-56
  • DOI: 10.1038/nmeth.4512
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Remarks] RIKEN PRIMe
  • URL: http://prime.psc.riken.jp/
• [Remarks] Computational mass spectrometry
  • URL: http://prime.psc.riken.jp/compms/index.html