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Elucidation of immune and allergic disease dynamics by integrative sequencing analysis

Research Project

Project/Area Number 22H00476
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Okada Yukinori  東京大学, 大学院医学系研究科(医学部), 教授 (70727411)

Co-Investigator(Kenkyū-buntansha) 奥野 龍禎  大阪大学, 大学院医学系研究科, 准教授 (00464248)
田中 良哉  産業医科大学, 医学部, 教授 (30248562)
駒形 嘉紀  杏林大学, 医学部, 教授 (60281995)
竹島 雄介  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (70893288)
熊坂 夏彦  東京大学, 医科学研究所, 教授 (80525527)
藤本 学  大阪大学, 大学院医学系研究科, 教授 (90272591)
王 青波  東京大学, 大学院医学系研究科(医学部), 客員研究員 (00916033)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥42,640,000 (Direct Cost: ¥32,800,000、Indirect Cost: ¥9,840,000)
Fiscal Year 2024: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2023: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2022: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Keywords遺伝統計学 / シングルセル / オミクス / 統合シークエンス解析 / シングルセルシークエンス / オミクス解析 / シングルセル解析 / 免疫アレルギー疾患 / 疾患ゲノム解析 / 次世代シークエンス / バイオインフォマティクス
Outline of Research at the Start

次世代シークエンス技術の発達に伴い、個人・疾患集団間で横断的にオミクス・シークエンス情報を統合し疾患病態を俯瞰する方法論(=統合シークエンス解析)の有用性が注目されている。本研究の目的は、最先端シークエンス技術で構築した免疫アレルギー疾患のオミクス情報を統合し、免疫機構の疾患特異的・動的・経時的な破綻像(=免疫ダイナミクス)を解明し、病態・発症機構を明らかにする点にある。多施設共同・診療科横断的レジストリを通じて多彩な免疫アレルギー疾患の生体試料・臨床情報を収集し、一細胞解析を主軸に多層的オミクス情報を構築する。

Outline of Final Research Achievements

In this study, we used state-of-the-art sequencing technology and integrated multi-layered omics information including genome, transcriptome, proteome, metabolome, and metagenome to elucidate the pathogenesis and pathological mechanisms of immunological allergic diseases. Under a nationwide multi-center collaborative research system, a registry of diverse diseases and healthy individuals was established, and the largest single-cell analysis in Japan was achieved, covering 900,000 cells in 150 individuals. In addition, they identified disease-specific biomarkers and therapeutic targets using deep learning and statistical analysis techniques, and provided a bird's-eye view of immuno-omics dynamics as a whole. In addition, he contributed to the training of young researchers in the field of genetic statistics.

Academic Significance and Societal Importance of the Research Achievements

本研究は、免疫アレルギー疾患に関する膨大なオミクス情報を統合解析することで、疾患の発症メカニズムや病態の多様性を明らかにし、学術的に新たな免疫疾患研究の枠組みを提示した点で大きな意義を持つ。特にシングルセル解析や深層学習の導入により、細胞レベルの動態把握と遺伝子変異の機能解明を高精度で実現した。また、得られた知見はバイオマーカーや創薬標的の発見につながり、今後の個別化医療や新規治療法開発に資するなど、社会的にも大きな貢献が期待される。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Comments on the Screening Results   Annual Research Report
  • Research Products

    (28 results)

All 2025 2024 2023 2022 2021

All Journal Article (28 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 28 results,  Open Access: 27 results)

  • [Journal Article] Blood DNA virome associates with autoimmune diseases and COVID-192025

    • Author(s)
      Sasa Noah、Kojima Shohei、Koide Rie、Hasegawa Takanori、Namkoong Ho、et al.
    • Journal Title

      Nature Genetics

      Volume: 57 Issue: 1 Pages: 65-79

    • DOI

      10.1038/s41588-024-02022-z

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer2025

    • Author(s)
      Sasa Noah、Kishikawa Toshihiro、Mori Masashi、Ito Rie、Mizoro Yumie、Suzuki Masami、Eguchi Hirotaka、Tanaka Hidenori、Fukusumi Takahito、Suzuki Motoyuki、Takenaka Yukinori、Nimura Keisuke、Okada Yukinori、Inohara Hidenori
    • Journal Title

      Nature Communications

      Volume: 16 Issue: 1 Pages: 1052-1052

    • DOI

      10.1038/s41467-025-56150-z

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder2025

    • Author(s)
      Yata Tomohiro、Sato Go、Ogawa Kotaro、Naito Tatsuhiko、Sonehara Kyuto、et al.
    • Journal Title

      Cell Genomics

      Volume: 5 Issue: 3 Pages: 100776-100776

    • DOI

      10.1016/j.xgen.2025.100776

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity2025

    • Author(s)
      Sonehara Kyuto、Uwamino Yoshifumi、Saiki Ryunosuke、et al.
    • Journal Title

      Cell Genomics

      Volume: 5 Issue: 3 Pages: 100783-100783

    • DOI

      10.1016/j.xgen.2025.100783

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases2025

    • Author(s)
      Yamamoto Yuji、Shirai Yuya、Sonehara Kyuto、Namba Shinichi、Ojima Takafumi、et al.
    • Journal Title

      Nature Communications

      Volume: 16 Issue: 1 Pages: 3765-3765

    • DOI

      10.1038/s41467-025-58149-y

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Body mass index stratification optimizes polygenic prediction of type 2 diabetes in cross-biobank analyses2024

    • Author(s)
      Ojima Takafumi、Namba Shinichi、Suzuki Ken、Yamamoto Kenichi、Sonehara Kyuto、Narita Akira、the Tohoku Medical Megabank Project Study Group、the Biobank Japan Project、Kamatani Yoichiro、Tamiya Gen、Yamamoto Masayuki、Yamauchi Toshimasa、Kadowaki Takashi、Okada Yukinori
    • Journal Title

      Nature Genetics

      Volume: 56 Issue: 6 Pages: 1100-1109

    • DOI

      10.1038/s41588-024-01782-y

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss2024

    • Author(s)
      Sonehara Kyuto、Yano Yoshitaka、Naito Tatsuhiko、Goto Shinobu、Yoshihara Hiroyuki、Otani Takahiro、Ozawa Fumiko、et al.
    • Journal Title

      Nature Communications

      Volume: 15 Issue: 1 Pages: 5744-5744

    • DOI

      10.1038/s41467-024-49993-5

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues2024

    • Author(s)
      Tomofuji Yoshihiko、Edahiro Ryuya、Sonehara Kyuto、Shirai Yuya、Kock Kian Hong、et al.
    • Journal Title

      Cell Genomics

      Volume: 4 Issue: 8 Pages: 100625-100625

    • DOI

      10.1016/j.xgen.2024.100625

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Machine learning reveals heterogeneous associations between environmental factors and cardiometabolic diseases across polygenic risk scores2024

    • Author(s)
      Naito Tatsuhiko、Inoue Kosuke、Namba Shinichi、Sonehara Kyuto、Suzuki Ken、BioBank Japan、Matsuda Koichi、Kondo Naoki、Toda Tatsushi、Yamauchi Toshimasa、Kadowaki Takashi、Okada Yukinori
    • Journal Title

      Communications Medicine

      Volume: 4 Issue: 1 Pages: 181-181

    • DOI

      10.1038/s43856-024-00596-7

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance2024

    • Author(s)
      Wang Qingbo S.、Hasegawa Takanori、Namkoong Ho、Saiki Ryunosuke、Edahiro Ryuya et al.
    • Journal Title

      Nature Genetics

      Volume: 56 Issue: 10 Pages: 2054-2067

    • DOI

      10.1038/s41588-024-01896-3

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inconsistent embryo selection across polygenic score methods2024

    • Author(s)
      Namba Shinichi、Akiyama Masato、Hamanoue Haruka、Kato Kazuto、Kawashima Minae、Kushima Itaru、et al.
    • Journal Title

      Nature Human Behaviour

      Volume: 8 Issue: 12 Pages: 2264-2267

    • DOI

      10.1038/s41562-024-02019-y

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic legacy of ancient hunter-gatherer Jomon in Japanese populations2024

    • Author(s)
      Yamamoto Kenichi,,,Gakuhari Takashi,,,Nakagome Shigeki, Okada Yukinori
    • Journal Title

      Nature Communications

      Volume: 15 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41467-024-54052-0

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity2023

    • Author(s)
      Japan COVID-19 Task Force
    • Journal Title

      Nature Genetics

      Volume: 55 Issue: 5 Pages: 753-767

    • DOI

      10.1038/s41588-023-01375-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of the personal information from human genome reads in gut metagenome sequencing data2023

    • Author(s)
      Tomofuji Yoshihiko、Sonehara Kyuto et al.
    • Journal Title

      Nature Microbiology

      Volume: 8 Issue: 6 Pages: 1079-1094

    • DOI

      10.1038/s41564-023-01381-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis2023

    • Author(s)
      Sato Go、Shirai Yuya、Namba Shinichi、Edahiro Ryuya、Sonehara Kyuto et al.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 3671-3671

    • DOI

      10.1038/s41467-023-39136-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis2023

    • Author(s)
      Akiyama Y、Sonehara K、Maeda D、Katoh H、Naito T、Yamamoto K、Morisaki T、Ishikawa S、Ushiku T、Kume H、Homma Y、Okada Y
    • Journal Title

      Cell Reports Medicine

      Volume: 4 Issue: 7 Pages: 101114-101114

    • DOI

      10.1016/j.xcrm.2023.101114

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multifaceted analysis of cross-tissue transcriptomes reveals phenotype-endotype associations in atopic dermatitis2023

    • Author(s)
      Sekita A, Kawasaki H, Fukushima-Nomura A, Yashiro K, Tanese K, Toshima S, Ashizaki K, Miyai T, Yazaki J Kobayashi A, Namba S, Naito T, Wang Q S., Kawakami E, Seita J, Ohara O, Sakurada K, Okada Y, Amagai M, Koseki H
    • Journal Title

      Nature Communications

      Volume: 14(1) Issue: 1 Pages: 6133-6133

    • DOI

      10.1038/s41467-023-41857-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population2023

    • Author(s)
      Tomofuji Yoshihiko、Kishikawa Toshihiro、Sonehara Kyuto et al.
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 11 Pages: 113324-113324

    • DOI

      10.1016/j.celrep.2023.113324

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases by cohort-wide immunophenotyping2023

    • Author(s)
      Tanaka Hiroaki、Okada Yukinori、Nakayamada Shingo、Miyazaki Yusuke、Sonehara Kyuto et al.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 83 Issue: 2 Pages: 242-252

    • DOI

      10.1136/ard-2023-224537

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Studies2023

    • Author(s)
      Naito Tatsuhiko、Inoue Kosuke、Sonehara Kyuto、Baba Ryuta、Kodama Takaya、Otagaki Yu、Okada Akira、Itcho Kiyotaka、Kobuke Kazuhiro、Kishimoto Shinji、Yamamoto Kenichi、Morisaki Takayuki、Higashi Yukihito、Hinata Nobuyuki、Arihiro Koji、Hattori Noboru、Okada Yukinori、Oki Kenji、BioBank Japan
    • Journal Title

      Circulation

      Volume: 147 Issue: 14 Pages: 1097-1109

    • DOI

      10.1161/circulationaha.122.062349

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts2023

    • Author(s)
      Wang Y, Namba S, Lopera E, Kerminen S, Tsuo K, Lall K, Kanai M, Zhou W, Wu KH, Fave MJ, Bhatta L, Awadalla P, Brumpton B, Deelen P, Hveem K, Lo FV, Magi R, Murakami Y, ..., Okada Y et al.
    • Journal Title

      Cell Genomics

      Volume: 3 Issue: 1 Pages: 100241-100241

    • DOI

      10.1016/j.xgen.2022.100241

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-trait and cross-population genome-wide association studies across autoimmune and allergic diseases identify shared and distinct genetic component2022

    • Author(s)
      Shirai Y, Nakanishi Y, Suzuki A, Konaka H, Nishikawa R, Sonehara K, Namba S, Tanaka H, Masuda T, Yaga M, Satoh S, Izumi M, Mizuno Y, Jo T, Maeda Y, Nii T, Oguro-Igashira E, Morisaki T, Kam, Nakayamada S, Nishigori C, Tanaka Y, Takeda Y, Yamamoto K, Kumanogoh A, Okada Y, The Biobank Japan Project
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 81 Issue: 9 Pages: 1301-1312

    • DOI

      10.1136/annrheumdis-2022-222460

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors2022

    • Author(s)
      Sonehara K、Kimura Y、Nakano Y、Ozawa T、Takahashi M、Suzuki K、Fujii T、Matsushita Y、Tomiyama A、Kishikawa T、Yamamoto K、Naito T、Suzuki T、Yamaguchi S、Miwa T、Sasaki H、Kitagawa M、Ohe N、Fukai J、Ogiwara H、Kawamura A、Miyawaki S、Matsuda F、Kiyokawa N、Ichimura K、Nishikawa R、Okada Y、Terashima K
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4478-4478

    • DOI

      10.1038/s41467-022-32005-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DOCK2 is involved in the host genetics and biology of severe COVID-192022

    • Author(s)
      Namkoong Ho、et al.
    • Journal Title

      Nature

      Volume: 609 Issue: 7928 Pages: 754-760

    • DOI

      10.1038/s41586-022-05163-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force2022

    • Author(s)
      Wang Qingbo S.、et al.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4830-4830

    • DOI

      10.1038/s41467-022-32276-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A saturated map of common genetic variants associated with human height2022

    • Author(s)
      Yengo L, Nakatochi M, Yamamoto K, Ichihara S, Yokota M, et al
    • Journal Title

      Nature

      Volume: 610 Issue: 7933 Pages: 704-712

    • DOI

      10.1038/s41586-022-05275-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis2022

    • Author(s)
      Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara KvYamaguchi K, Amariuta T, Too CL, Laufer VA, Scott IC, Viatte S, Takahashi M, Ohmura K, Murasawa A, Hashimoto M, Ito H, ..., Okada Y et al.
    • Journal Title

      Nature Genetics

      Volume: 54 Issue: 11 Pages: 1640-1651

    • DOI

      10.1038/s41588-022-01213-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic architecture of microRNA expression and its link to complex diseases in the Japanese population2021

    • Author(s)
      Sonehara Kyuto、Sakaue Saori、Maeda Yuichi、Hirata Jun、Kishikawa Toshihiro、Yamamoto Kenichi、Matsuoka Hidetoshi、Yoshimura Maiko、Nii Takuro、Ohshima Shiro、Kumanogoh Atsushi、Okada Yukinori
    • Journal Title

      Human Molecular Genetics

      Volume: - Issue: 11 Pages: 1806-1820

    • DOI

      10.1093/hmg/ddab361

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2022-04-19   Modified: 2026-01-16  

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