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

• Project/Area Number: 18H03328
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: The 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: ¥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。

Research Products

• [Int'l Joint Research] ICGC/TCGA(米国)
• [Int'l Joint Research] ICGC/TCGA(カナダ)
• [Int'l Joint Research] ICGC/TCGA(中国)
• [Int'l Joint Research] ICGC/TCGA(韓国)
• [Int'l Joint Research] ICGC/TCGA(ドイツ)
• [Int'l Joint Research]
• [Journal Article] Comprehensive molecular analysis of genomic profiles and PD-L1 expression in lung adenocarcinoma with a high-grade fetal adenocarcinoma component (2021)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Halcyon: an accurate basecaller exploiting an encoder?decoder model with monotonic attention (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Global gene network exploration based on explainable artificial intelligence approach (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Theoretical foundation of the performance of phylogeny-based somatic variant detection (2020)
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in oncogenic mutational processes (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples (2020)
  • 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
  • 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 Types (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pan-cancer analysis of whole genomes (2020)
  • 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
  • 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
  • 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
  • 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 learning (2019)
  • 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
  • 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 Data (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] ALPHLARD: a Bayesian method for analyzing HLA genes from whole genome sequence data (2018)
  • 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
  • Peer Reviewed / Open Access
• [Presentation] Immuno-genomics pancancer landscape reveals diverse immune escape mechanisms and immune-editing histories (2018)
  • Author(s): Seiya Imoto
  • Organizer: Biomedical Sciences in the Era of Big Data
  • Int'l Joint Research / Invited
• [Presentation] Cancer Immunogenomics Analysis of ICGC/PCAWG (2018)
  • Author(s): Seiya Imoto
  • Organizer: The 77th Annual Meeting of the Japanese Cancer Association
  • 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
• [Book] Precision Medicine (2020)
  • Author(s): 井元清哉
  • Total Pages: 6
  • Publisher: ニュー・サイエンス社
• [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