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Bayesian Modeling for Understanding Systems of Immune Responses and Revealing Immune Escape Mechanisms

Research Project

Project/Area Number 18H03328
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) 中川 英刀  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 (50361621)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywordsベイズモデル / 免疫システム / HLA / ネオ抗原
Outline of Final Research Achievements

The following results were obtained regarding the development of data analysis techniques for understanding the complex human immune system that monitors cancer immunity. Although the accuracy of HLA genotyping from whole genome sequencing data was extremely low, we achieved 98% accuracy by constructing a new Bayesian statistical model. Furthermore, we have developed a method to accurately identify new HLA genotypes and somatic mutations in HLA genes that are not registered in the database. In addition, we have developed and released an application named Neoantimon for the identification of somatic neoantigens that bind to patient HLA and are presented to T cells. Based on these technologies, we have developed a new index, IEI, which can be used to analyze how each patient's cancer tissue has been subjected to selective pressure from the immune system.

Academic Significance and Societal Importance of the Research Achievements

開発したデータ解析技術群は、大型計算機環境を必要とするが、研究代表者が所属するヒトゲノム解析センターのスパコンSHIROKANE上に実装されているため、多くの研究者が免疫ゲノム解析を行うことが可能となり、研究分野の活性化に繋がる。開発した技術群は、患者の癌の免疫学的と級長を炙り出すことが出来る。免疫細胞が浸潤した体細胞変異の多い癌は免疫チェックポイントインヒビターなどの免疫療法が有効であることが知られている。一方、そのような免疫療法が有効ではない癌の特徴を開発した方法を駆使しその共通性を見出すことで、難治癌に対する新しい免疫学的な治療法を開発するシーズになることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (15 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (3 results)

  • [Int'l Joint Research] ICGC/TCGA(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ICGC/TCGA(カナダ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ICGC/TCGA(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ICGC/TCGA(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ICGC/TCGA(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Comprehensive molecular analysis of genomic profiles and PD-L1 expression in lung adenocarcinoma with a high-grade fetal adenocarcinoma component2021

    • Author(s)
      Masaki Suzuki, Rika Kasajima, Tomoyuki Yokose, Hiroyuki Ito, Eigo Shimizu, Seira Hatakeyama, Kazuaki Yokoyama, Rui Yamaguchi, Yoichi Furukawa, Satoru Miyano, Seiya Imoto, Emi Yoshioka, Kota Washimi, Yoichiro Okubo, Kae Kawachi, Shinya Sato, Yohei Miyagi
    • Journal Title

      Translational Lung Cancer Research

      Volume: 10 Issue: 3 Pages: 1292-1304

    • DOI

      10.21037/tlcr-20-1158

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Halcyon: an accurate basecaller exploiting an encoder?decoder model with monotonic attention2020

    • Author(s)
      Konishi Hiroki、Yamaguchi Rui、Yamaguchi Kiyoshi、Furukawa Yoichi、Imoto Seiya
    • Journal Title

      Bioinformatics

      Volume: online first Issue: 9 Pages: 1211-1217

    • DOI

      10.1093/bioinformatics/btaa953

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Global gene network exploration based on explainable artificial intelligence approach2020

    • Author(s)
      Park Heewon、Maruhashi Koji、Yamaguchi Rui、Imoto Seiya、Miyano Satoru
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0241508-e0241508

    • DOI

      10.1371/journal.pone.0241508

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Theoretical foundation of the performance of phylogeny-based somatic variant detection2020

    • Author(s)
      Moriyama T, Imoto S, Miyano S, Yamaguchi R.
    • Journal Title

      Proc. 2nd International Symposium on Mathematical and Computational Oncology

      Volume: 12508 Pages: 87-101

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neoantimon: A multifunctional R package for identification of tumor-specific neoantigens.2020

    • Author(s)
      Hasegawa T, Hayashi S, Nakagawa H, Miyano S, and Imoto S.
    • Journal Title

      Bioinformatics

      Volume: 36 Issue: 18 Pages: 4813-4816

    • DOI

      10.1093/bioinformatics/btaa616

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex differences in oncogenic mutational processes2020

    • Author(s)
      Li Constance H.、PCAWG Tumour Subtypes and Clinical Translation、Prokopec Stephenie D.、Sun Ren X.、Yousif Fouad、Schmitz Nathaniel、Boutros Paul C.、PCAWG Consortium
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 4330-4330

    • DOI

      10.1038/s41467-020-17359-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples2020

    • Author(s)
      Bailey Matthew H., et al.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 4748-4748

    • DOI

      10.1038/s41467-020-18151-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive Analysis of Indels in Whole-genome Microsatellite Regions and Microsatellite Instability across 21 Cancer Types2020

    • Author(s)
      Fujimoto A*, Fujita M, Hasegawa T, Wong JH, Maejima K, Oku-Sasaki A, Nakano K, Shiraishi Y, Miyano S, Yamamoto G, Akagi K, Imoto S, and Nakagawa H
    • Journal Title

      Genome Research

      Volume: 30 Issue: 3 Pages: 334-34

    • DOI

      10.1101/gr.255026.119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pan-cancer analysis of whole genomes2020

    • Author(s)
      The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
    • Journal Title

      Nature

      Volume: 578 Issue: 7793 Pages: 82-93

    • DOI

      10.1038/s41586-020-1969-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations.2020

    • Author(s)
      Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
    • Journal Title

      EBioMedicine

      Volume: 53 Pages: 102659-102659

    • DOI

      10.1016/j.ebiom.2020.102659

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantifying immune-based counterselection of somatic mutations.2019

    • Author(s)
      Yang F, Kim DK, Nakagawa H, Hayashi S, Imoto S, Stein L, and Roth F
    • Journal Title

      PLoS Genet

      Volume: 15 Issue: 7 Pages: e1008227-e1008227

    • DOI

      10.1371/journal.pgen.1008227

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Capturing the differences between humoral immunity in the normal and tumor environments from repertoire-seq of B-cell receptors using supervised machine learning2019

    • Author(s)
      Konishi H, Komura D, Katoh H, Atsumi S, Koda H, Yamamoto A, Seto Y, Fukayama M, Yamaguchi R, Imoto S, Ishikawa S.
    • Journal Title

      BMC Bioinformatics

      Volume: 20(1) Issue: 1 Pages: 267-267

    • DOI

      10.1186/s12859-019-2853-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALPHLARD-NT: Bayesian Method for Human Leukocyte Antigen Genotyping and Mutation Calling through Simultaneous Analysis of Normal and Tumor Whole-Genome Sequence Data2019

    • Author(s)
      Hayashi S, Moriyama T, Yamaguchi R, Mizuno S, Komura M, Miyano S, Nakagawa H, Imoto S
    • Journal Title

      J Comput Biol.

      Volume: 26(9) Issue: 9 Pages: 923-937

    • DOI

      10.1089/cmb.2018.0224

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance2019

    • Author(s)
      Muraoka Daisuke、Seo Naohiro、Hayashi Tae、Tahara Yoshiro、Fujii Keisuke、Tawara Isao、Miyahara Yoshihiro、Okamori Kana、Yagita Hideo、Imoto Seiya、Yamaguchi Rui、Komura Mitsuhiro、Miyano Satoru、Goto Masahiro、Sawada Shin-ichi、Asai Akira、Ikeda Hiroaki、Akiyoshi Kazunari、Harada Naozumi、Shiku Hiroshi
    • Journal Title

      Journal of Clinical Investigation

      Volume: 129 Issue: 3 Pages: 1278-1294

    • DOI

      10.1172/jci97642

    • NAID

      120006987781

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALPHLARD: a Bayesian method for analyzing HLA genes from whole genome sequence data2018

    • Author(s)
      Hayashi S, Yamaguchi R, Mizuno S, Komura M, Miyano S, Nakagawa H, Imoto S
    • Journal Title

      BMC Genomics

      Volume: 19(1) Issue: 1 Pages: 790-790

    • DOI

      10.1186/s12864-018-5169-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Immuno-genomics pancancer landscape reveals diverse immune escape mechanisms and immune-editing histories2018

    • Author(s)
      Seiya Imoto
    • Organizer
      Biomedical Sciences in the Era of Big Data
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer Immunogenomics Analysis of ICGC/PCAWG2018

    • Author(s)
      Seiya Imoto
    • Organizer
      The 77th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 日本内科学会誌2021

    • Author(s)
      井元清哉
    • Total Pages
      7
    • Publisher
      日本内科学会
    • Related Report
      2020 Annual Research Report
  • [Book] Precision Medicine2020

    • Author(s)
      井元清哉
    • Total Pages
      6
    • Publisher
      ニュー・サイエンス社
    • Related Report
      2020 Annual Research Report
  • [Book] T細胞受容体レパトア解析2018

    • Author(s)
      井元清哉, 長谷川嵩矩, 山口類
    • Total Pages
      5
    • Publisher
      メディカルドゥ
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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