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Development of Information Base Technology for Evaluation of Organ Functions of Intestinal Microbiota by Disease Metagenomics

Research Project

Project/Area Number 21H03538
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 InstitutionThe University of Tokyo

Principal Investigator

Imoto Seiya  東京大学, 医科学研究所, 教授 (10345027)

Co-Investigator(Kenkyū-buntansha) 湯上 伸弘  富士通株式会社(富士通研究所), その他部局等, 研究員 (30417183)
植松 智  大阪公立大学, 大学院医学研究科, 教授 (50379088)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsメタゲノム解析 / AI / 腸内細菌叢 / 腸内ウイルス叢 / 宿主寄生体感染関係 / ショットガンメタゲノム解析 / メタゲノム診断AI
Outline of Research at the Start

腸内細菌叢は非自己の成分の集合体でありながら、ヒト遺伝子と分業的協業的にあたかも「臓器」の様に振る舞うことが明らかとなってきた。更に、腸内に細菌以上に生息する共生ウイルスは、細菌に感染するバクテリオファージであり、腸内で細菌叢とエコシステムを形成するがその全貌は明らかではなかった。様々な疾患においてショットガンメタゲノム解析によって腸内細菌叢・ウイルス叢のデータを取得し、臓器機能を評価できるメタゲノム診断AIを構築する。疾患特異的に欠損、及び活性化しているパスウェイの同定と、個々のパスウェイに関わる腸内細菌及びその細菌に特異的に感染する腸内ファージの同定を行うための情報基盤技術を構築する。

Outline of Final Research Achievements

We have performed metagenomic analysis of bacterial and phage flora in several typical diseases associated with dysbiosis and developed technologies to extract functional pathways associated with disease onset and progression. Furthermore, to correct this, we have successfully developed a technology to search for phage-derived enzymes that can infect and lyse symbiotic pathogenic bacteria from metagenomic data, and a new information analysis technology based on contrastive learning to predict host bacteria of phages. Furthermore, tools for interpreting the results of metagenome analysis based on comprehensive database information were developed and released. Using these technologies, we have elucidated the healing mechanism of recurrent C. difficile-associated enterocolitis and analyzed the bacteria responsible for the odor of axillary dysbiosis at the genetic level.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌の構成異常によるさまざまな疾患に対する新たな治療法としてのファージ療法の開発につながる研究成果を得た。この技術は、メタゲノムデータを基盤とすることで、難培養性細菌やファージを対象とすることができ、現在、社会の脅威となっている多剤耐性菌に対する有力な対策となることが期待できる。

Report

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

    (20 results)

All 2024 2023 2022 2021

All Journal Article (17 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 15 results) Presentation (3 results) (of which Invited: 3 results)

  • [Journal Article] Targeted lysis of Staphylococcus hominis linked to axillary osmidrosis using bacteriophage-derived endolysin2024

    • Author(s)
      Watanabe Miki、Uematsu Miho、Fujimoto Kosuke、Hara Takeshi、Yamamoto Mako、Miyaoka Daichi、Yokota Chieko、Kamei Yukari、Sugimoto Akira、Kawasaki Natsuko、Yabuno Takato、Sato Noriaki、Sato Shintaro、Yamaguchi Kiyoshi、Furukawa Yoichi、Tsuruta Daisuke、Okada Fumihiro、Imoto Seiya、Uematsu Satoshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: - Issue: 11 Pages: 2577-2581

    • DOI

      10.1016/j.jid.2024.03.039

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Definition of a Dietary Pattern Expressing the Intake of Vegetables and Fruits and Its Association with Intestinal Microbiota2023

    • Author(s)
      Yamauchi Toshitaka、Koyama Naoko、Hirai Ayumi、Suganuma Hiroyuki、Suzuki Shigenori、Murashita Koichi、Mikami Tatsuya、Tamada Yoshinori、Sato Noriaki、Imoto Seiya、Itoh Ken、Nakaji Shigeyuki
    • Journal Title

      Nutrients

      Volume: 15 Issue: 9 Pages: 2104-2104

    • DOI

      10.3390/nu15092104

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zero-shot-capable identification of phage?host relationships with whole-genome sequence representation by contrastive learning2023

    • Author(s)
      Zhang Yao-zhong、Liu Yunjie、Bai Zeheng、Fujimoto Kosuke、Uematsu Satoshi、Imoto Seiya
    • Journal Title

      Briefings in Bioinformatics

      Volume: 24 Issue: 5 Pages: 1-10

    • DOI

      10.1093/bib/bbad239

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microbial Gene Ontology informed deep neural network for microbe functionality discovery in human diseases2023

    • Author(s)
      Liu Yunjie、Zhang Yao-zhong、Imoto Seiya
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 8 Pages: 1-13

    • DOI

      10.1371/journal.pone.0290307

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of the BERT model on nucleotide sequences with non-standard pre-training and evaluation of different k-mer embeddings2023

    • Author(s)
      Zhang Yao-zhong、Bai Zeheng、Imoto Seiya
    • Journal Title

      Bioinformatics

      Volume: 39 Issue: 10 Pages: 1-10

    • DOI

      10.1093/bioinformatics/btad617

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ggkegg: analysis and visualization of KEGG data utilizing the grammar of graphics.2023

    • Author(s)
      Sato N, Uematsu M, Fujimoto K, Uematsu S, Imoto S.
    • Journal Title

      Bioinformatics

      Volume: 39 Issue: 10

    • DOI

      10.1093/bioinformatics/btad622

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preemptive Intravenous Human Immunoglobulin G Suppresses BK Polyomavirus Replication and Spread of Infection In Vitro2023

    • Author(s)
      Sato Noriaki、Shiraki Atsuko、Mori Keita P.、Sakai Kaoru、Takemura Yoshinori、Yanagita Motoko、Imoto Seiya、Tanabe Kazunari、Shiraki Kimiyasu
    • Journal Title

      American Journal of Transplantation

      Volume: - Issue: 5 Pages: 862-866

    • DOI

      10.1016/j.ajt.2023.11.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imputing time-series microbiome abundance profiles with diffusion model2023

    • Author(s)
      Seki Misato、Zhang Yao-Zhong、Imoto Seiya
    • Journal Title

      IEEE Xplore

      Volume: BIBM 2023 Pages: 914-919

    • DOI

      10.1109/bibm58861.2023.10385703

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma2023

    • Author(s)
      Takaori Ayaka、Hashimoto Daisuke、Ikeura Tsukasa、Ito Takashi、Nakamaru Koh、Masuda Masataka、Nakayama Shinji、Yamaki So、Yamamoto Tomohisa、Fujimoto Kosuke、Matsuo Yoshiyuki、Akagawa Shohei、Ishida Mitsuaki、Yamaguchi Kiyoshi、Imoto Seiya、Hirota Kiichi、Uematsu Satoshi、Satoi Sohei、Sekimoto Mitsugu、Naganuma Makoto
    • Journal Title

      Pancreatology

      Volume: - Issue: 4 Pages: 367-376

    • DOI

      10.1016/j.pan.2023.04.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer2022

    • Author(s)
      Masuhiro Kentaro、Tamiya Motohiro、Fujimoto Kosuke
    • Journal Title

      JCI Insight

      Volume: 1 Issue: 9 Pages: 1-1

    • DOI

      10.1172/jci.insight.157915

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of bacteriophage genome sequences with representation learning2022

    • Author(s)
      Bai Zeheng、Zhang Yao-zhong、Miyano Satoru、Yamaguchi Rui、Fujimoto Kosuke、Uematsu Satoshi、Imoto Seiya
    • Journal Title

      Bioinformatics

      Volume: 38 Issue: 18 Pages: 4264-4270

    • DOI

      10.1093/bioinformatics/btac509

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two Blautia Species Associated with Visceral Fat Accumulation: A One-Year Longitudinal Study2022

    • Author(s)
      Ozato Naoki、Yamaguchi Tohru、Mori Kenta、Katashima Mitsuhiro、Kumagai Mika、Murashita Koichi、Katsuragi Yoshihisa、Tamada Yoshinori、Kakuta Masanori、Imoto Seiya、Ihara Kazushige、Nakaji Shigeyuki
    • Journal Title

      Biology

      Volume: 11 Issue: 2 Pages: 318-318

    • DOI

      10.3390/biology11020318

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice2021

    • Author(s)
      Kosaka Satoshi、Nadatani Yuji、Higashimori Akira、Otani Koji、Fujimoto Kosuke、Nagata Yuki、Ominami Masaki、Fukunaga Shusei、Hosomi Shuhei、Kamata Noriko、Tanaka Fumio、Nagami Yasuaki、Taira Koichi、Imoto Seiya、Uematsu Satoshi、Watanabe Toshio、Fujiwara Yasuhiro
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 12 Pages: 2563-2563

    • DOI

      10.3390/microorganisms9122563

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovering microbe functionality in human disease with a gene-ontology-aware model2021

    • Author(s)
      Liu Y, Zhang Y-Z, Imoto S.
    • Journal Title

      Proc. Biological Ontologies and Knowledge Bases

      Volume: - Pages: 1873-1880

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial2021

    • Author(s)
      Yuki Yoshikazu、Nojima Masanori、Hosono Osamu、Tanaka Hirotoshi、Kimura Yasumasa、Satoh Takeshi、Imoto Seiya、Uematsu Satoshi、Kurokawa Shiho、Kashima Koji、Mejima Mio、Nakahashi-Ouchida Rika、Uchida Yohei、Marui Takanori、Yoshikawa Noritada、Nagamura Fumitaka、Fujihashi Kohtaro、Kiyono Hiroshi
    • Journal Title

      The Lancet Microbe

      Volume: 2 Issue: 9 Pages: 30196-8

    • DOI

      10.1016/s2666-5247(20)30196-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana2021

    • Author(s)
      Parbie Prince Kofi、Mizutani Taketoshi、Ishizaka Aya、Kawana-Tachikawa Ai、Runtuwene Lucky Ronald、Seki Sayuri、Abana Christopher Zaab-Yen、Kushitor Dennis、Bonney Evelyn Yayra、Ofori Sampson Badu、Uematsu Satoshi、Imoto Seiya、Kimura Yasumasa、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William Kwabena、Matano Tetsuro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 646467-646467

    • DOI

      10.3389/fcimb.2021.646467

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation2021

    • Author(s)
      Fujimoto, Kosuke, et al.
    • Journal Title

      Gastroenterology

      Volume: - Issue: 6 Pages: 400-405

    • DOI

      10.1053/j.gastro.2021.02.013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Human Genomics and Metagenomics for Creating Future Medicine2023

    • Author(s)
      Seiya Imoto
    • Organizer
      Science Forum Microsoft Research AI4Science
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Metagenomics: a Paradigm Shift in Health/Medical Care2022

    • Author(s)
      Seiya Imoto
    • Organizer
      RIEC International Symposium
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Metagenome Analysis Leads a Paradigm Shift in Health/Medical Care2021

    • Author(s)
      井元清哉
    • Organizer
      日本免疫学会
    • Related Report
      2021 Annual Research Report
    • Invited

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

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