Establishment of new diagnostic method for HTLV-1 related diseases using MinION nanopore sequencer

• Project/Area Number: 17K15044
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: Firouzi Sanaz 東京大学, 大学院新領域創成科学研究科, 客員共同研究員 (30793400)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: HTLV-1 / ATL / Personalized Medicine / Molecular Diagnosis / Nanopore Sequencer / Intratumor Heterogeneity / TCR clonality / Clonality analysis / Integration Site / Nanopore sequencing / MinION sequencer / NGS technology / Clonality / Genomics

Outline of Final Research Achievements

This study, using multi-omics approaches, in pursuit of determining potential biomarkers for disease development could achieve following findings: ①Clonality analysis based on provirus integration sites using NGS technology suggested possible applications of clonality in the molecular diagnosis of ATL, as well as predicting ATL development among HTLV-1-infected individuals (Blood advances 2017 and Human genomics 2017)②Development of a new methodology for easy-to-do, rapid and cheap enough analysis of clonality using MinIon sequencer③Showing presence of a high degree of intra-tumor heterogeneity(ITH) based on mutations among ATL patients using Whole Exome Sequencing(Neoplasia 2018).④determining TCR clonality by RNA sequencing might be useful for prognostic purposes and for personalizing ATL diagnosis and assessment of treatments(npj Gen. med.2019).

Academic Significance and Societal Importance of the Research Achievements

我々は当研究の結果を4つの査読有学術雑誌や国内外の学会に発表することができた。
また得られた研究結果はATL・その他HTLV-1関連疾患における診断、予後予測、治療および個別化医療の実現への道を開いた。これらの研究成果を応じて本研究は世界の学術研究の進展または日本だけではなく世界中のHTLV-1感染患者の命と暮らしに貢献し続けることができる。

Research Products

• [Int'l Joint Research] University of Muenster(ドイツ)
• [Int'l Joint Research] Institute of Bioinformatics/Faculty of Medicine/University of Muenster(Germany)
• [Journal Article] RNA sequencing identifies clonal structure of T-cell repertoires in patients with adult T-cell leukemia/lymphoma (2019)
  • Author(s): Farmanbar Amir、Kneller Robert、Firouzi Sanaz
  • Journal Title: npj Genomic Medicine Volume: 4 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41525-019-0084-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutational Intratumor Heterogeneity is a Complex and Early Event in the Development of Adult T-cell Leukemia/Lymphoma. (2018)
  • Author(s): Amir Farmanbar, Sanaz Firouzi, Wojciech Makalowski, Robert Kneller, Masako Iwanaga, Atae Utsunomiya, Kenta Nakai, Toshiki Watanabe.
  • Journal Title: Neoplasia Volume: 9 Issue: 9 Pages: 883-893
  • DOI: 10.1016/j.neo.2018.07.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonality of HTLV-1 infected T cells as a risk indicator for development and progression of adult T-cell leukemia (2017)
  • Author(s): Firouzi Sanaz、Farmanbar Amir、Nakai Kenta、Iwanaga Masako、Uchimaru Kaoru、Utsunomiya Atae、Suzuki Yutaka、Watanabe Toshiki
  • Journal Title: Blood Advances Volume: 1 Issue: 15 Pages: 1195-1205
  • DOI: 10.1182/bloodadvances.2017005900
  • Peer Reviewed / Open Access
• [Journal Article] Inferring clonal structure in HTLV-1-infected individuals: towards bridging the gap between analysis and visualization (2017)
  • Author(s): Farmanbar Amir、Firouzi Sanaz(Equal first author and corresponding author)、Makalowski Wojciech、Iwanaga Masako、Uchimaru Kaoru、Utsunomiya Atae、Watanabe Toshiki、Nakai Kenta
  • Journal Title: Human Genomics Volume: 11 Issue: 1 Pages: 1-15
  • DOI: 10.1186/s40246-017-0112-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. (2017)
  • Author(s): Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh K, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, et al.
  • Journal Title: J Clin Microbiol. Volume: 55(9) Issue: 9 Pages: 2838-2849
  • DOI: 10.1128/jcm.00659-17
  • Peer Reviewed / Open Access
• [Presentation] Multidisciplinary approaches reveal a complex intratumor heterogeneity in adult T-cell leukemia/lymphoma (2018)
  • Author(s): Sanaz Firouzi, Amir Farmanbar, Robert Kneller, Wojciech Makalowski, Kenta Nakai, Toshiki Watanabe and Sumio Sugano
  • Organizer: International Society for Computational Biology And Bioinformatics(ISCB) conference
  • Int'l Joint Research
• [Presentation] Analysis of Intra-Tumor Heterogeneity in Adult T-Cell Leukemia (2018)
  • Author(s): Amir Farmanbar, Sanaz Firouzi, Kenta Nakai
  • Organizer: 45th Annual Meeting of IMUSUT
• [Presentation] Monitoring clonality of HTLV-1 infected cells using provirus integration sites by Oxford Nanopore MinIon sequencer (2017)
  • Author(s): Firouzi Sanaz
  • Organizer: JSPS Core-to-Core Program "Training Seminar for MinION"
  • Invited