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Development of a novel method for de novo sequencing of amino acid sequences by mass spectrometry

Research Project

Project/Area Number 20H03245
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43060:System genome science-related
Research InstitutionToyama University of International Studies

Principal Investigator

Kawano Shin  富山国際大学, 現代社会学部, 教授 (40470075)

Co-Investigator(Kenkyū-buntansha) 岩崎 未央  京都大学, iPS細胞研究所, 講師 (10722811)
小林 大樹  新潟大学, 医歯学系, 助教 (20448517)
吉沢 明康  京都大学, 薬学研究科, 特定助教 (70551159)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsタンパク質 / 質量分析 / アミノ酸配列決定 / アミノ酸組成分析 / de novo sequencing / プロテオーム
Outline of Research at the Start

アミノ酸配列を質量分析によって決定する新規de novo sequencing (de novo決定) 法を開発する。de novo決定法は一般的なデータベース検索法と異なりゲノム情報が不要で、アミノ酸を一残基ずつ確定するため精度が高いが、探索空間が膨大なため最適解が得にくい。本申請課題ではペプチドのマススペクトルに加えて、アミノ酸組成などの物性情報も実験的に取得し併用することで大幅に探索空間を限定し、現実的な計算時間でde novo決定を行う手法を開発する。この手法によって、ゲノム情報を用いないタンパク質同定のほか、ゲノムにコードされない抗体可変領域の配列決定などへの応用が期待される。

Outline of Final Research Achievements

In this study, we developed a novel method to determine amino acid sequences using only mass spectrometry data without known sequences. In general, the identification method that does not use known sequence information has a huge search space, making it difficult to obtain an optimal solution. Thus, by utilizing the physical property information of the amino acid sequence, the search space is greatly limited, and the calculation can be completed in a realistic calculation time. We investigated the physical property information of amino acid sequence and decided to utilize the amino acid composition and the retention time of high-performance liquid chromatography. Based on the benchmark results, we concluded that the strategy of first determining the partial amino acid sequence information of the peptide sequence when constructing the resulting candidate sequence is effective. We developed a novel method using these elements.

Academic Significance and Societal Importance of the Research Achievements

現在、疾患研究を含む医学研究ではプロテオーム解析の重要性が高まっている。しかしプロテオーム・データの解析ではゲノム情報に基づく既知配列しか探知できず、測定データの3割程度しか同定ができていない。癌のように変異が多い場合には既知配列が利用できないが、このような場合に用いる特殊な同定方法では、既存の代表的なソフトウェアを用いても正解率は4割程度である。本研究では、今まで用いられてこなかった情報を補助的に用いることで正解率を上げる手法を開発しており、今後の疾患タンパク質研究や抗体医薬などの応用研究への進展が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (22 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (6 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results)

  • [Int'l Joint Research] European Bioinformatics Institute(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Institute for Systems Biology/University of California San Diego(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] European Bioinformatics Institute(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Institute for Systems Biology/University of California San Diego(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] European Bioinformatics Institute(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Institute for Systems Biology/University of California San Diego(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Proteomics Standards Initiative at Twenty Years: Current Activities and Future Work2023

    • Author(s)
      Deutsch EW,Vizcaino JA,Jones AR,Binz PA,Lam H,Klein J,Bittremieux W,Perez-Riverol Y,Tabb DL,Walzer M,Ricard-Blum S,Hermjakob H,Neumann S,Mak TD,Kawano S,Mendoza L,Van Den Bossche T,Gabriels R,Bandeira N,Carver J,Pullman B,Sun Z,Hoffmann N,Shofstahl J,Zhu Y,Licata L,Quaglia F,Tosatto SCE,Orchard SE
    • Journal Title

      Journal of Proteome Research

      Volume: 22 Issue: 2 Pages: 287-301

    • DOI

      10.1021/acs.jproteome.2c00637

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The ProteomeXchange consortium at 10 years: 2023 update2022

    • Author(s)
      Deutsch EW、Bandeira N、Perez-Riverol Y、Sharma V、Carver JJ、Mendoza L、Kundu DJ、Wang S、Bandla C、Kamatchinathan S、Hewapathirana S、Pullman BS、Wertz J、Sun Z、Kawano S、Okuda S、Watanabe Y、MacLean B、MacCoss MJ、Zhu Y、Ishihama Y、Vizcaino JA
    • Journal Title

      Nucleic Acids Research

      Volume: 51 Issue: D1 Pages: D1539-D1548

    • DOI

      10.1093/nar/gkac1040

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteomics Standards Initiative’s ProForma 2.0: Unifying the Encoding of Proteoforms and Peptidoforms2022

    • Author(s)
      LeDuc Richard D.、Deutsch Eric W.、Binz Pierre-Alain、Fellers Ryan T.、Cesnik Anthony J.、Klein Joshua A.、Van Den Bossche Tim、Gabriels Ralf、Yalavarthi Arshika、Perez-Riverol Yasset、Carver Jeremy、Bittremieux Wout、Kawano Shin、Pullman Benjamin、Bandeira Nuno、Kelleher Neil L.、Thomas Paul M.、Vizca?no Juan Antonio
    • Journal Title

      Journal of Proteome Research

      Volume: 21 Issue: 4 Pages: 1189-1195

    • DOI

      10.1021/acs.jproteome.1c00771

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Universal Spectrum Identifier for mass spectra2021

    • Author(s)
      Deutsch Eric W.、Perez-Riverol Yasset、Carver Jeremy、Kawano Shin、Mendoza Luis、Van Den Bossche Tim、Gabriels Ralf、Binz Pierre-Alain、Pullman Benjamin、Sun Zhi、Shofstahl Jim、Bittremieux Wout、Mak Tytus D.、Klein Joshua、Zhu Yunping、Lam Henry、Vizca?no Juan Antonio、Bandeira Nuno
    • Journal Title

      Nature Methods

      Volume: 18 Issue: 7 Pages: 768-770

    • DOI

      10.1038/s41592-021-01184-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Proteomics Standards Initiatives ProForma 2.0 Unifying the encoding of Proteoforms and Peptidoforms2021

    • Author(s)
      Richard D. LeDuc, Eric W. Deutsch, Pierre-Alain Binz, Ryan T. Fellers, Anthony J. Cesnik, Joshua A. Klein, Tim Van Den Bossche, Ralf Gabriels, Arshika Yalavarthi, Yasset Perez-Riverol, Jeremy Carver, Wout Bittremieux, Shin Kawano, Benjamin Pullman, Nuno Bandeira, Neil L. Kelleher, Paul M. Thomas, Juan Antonio Vizcaino
    • Journal Title

      arXiv

      Volume: 2109 Pages: 1-61

    • Related Report
      2021 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Universal Spectrum Identifier for mass spectra2020

    • Author(s)
      Deutsch Eric W., Perez-Riverol Yasset, Carver Jeremy, Kawano Shin, Mendoza Luis, Van Den Bossche Tim, Gabriels Ralf, Binz Pierre-Alain, Pullman Benjamin, Sun Zhi, Shofstahl Jim, Bittremieux Wout, Mak Tytus D., Klein Joshua, Zhu Yunping, Lam Henry, Vizcaino Juan Antonio, Bandeira Nuno
    • Journal Title

      bioRxiv

      Volume: 415539 Pages: 1-4

    • DOI

      10.1101/2020.12.07.415539

    • Related Report
      2020 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Presentation] プロテオームデータの収集と標準化2023

    • Author(s)
      河野 信
    • Organizer
      疾患プロテオミクス研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Mass++ ver.4 -MS data viewer meets online databases-2022

    • Author(s)
      Satoshi Tanaka, Masaki Murase, Masaki Kato, Hiroyuki Yamamoto, Tsuyoshi Tabata, Maiko Kusano, Shin Kawano, Susumu Goto, Yasushi Ishihama, Akiyasu C. Yoshizawa
    • Organizer
      The HUPO 2022 Congress
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] jPOSTの現状とプロテミクスデータの標準化に向けた国際連携2021

    • Author(s)
      河野信
    • Organizer
      日本プロテオーム学会2021年大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The HUPO-PSI Universal Spectrum Identifier (USI) for mass spectra2021

    • Author(s)
      Tim Van Den Bossche, Eric W. Deutsch, Yasset Perez-Riverol, Jeremy Carver, Shin Kawano, Luis Mendoza, Ralf Gabriels, Pierre-Alain Binz, Benjamin Pullman, Zhi Sun, Jim Shofstahl, Wout Bittremieux, Tytus D. Mak, Joshua Klein, Yunping Zhu, Henry Lam, Juan Antonio Vizcaino, and Nuno Bandeira
    • Organizer
      HUPO reconnect 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マススペクトルに於けるペプチドイオンピークの深層学習による検出法の開発2021

    • Author(s)
      吉沢明康
    • Organizer
      第17回日本臨床プロテオゲノミクス研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] jPOSTdb: COVID-19データベースの構築2021

    • Author(s)
      吉沢明康,守屋勇樹,小林大樹,張智翔,奥田修二郎,田畑剛,河野信,幡野敦,高見知代,松本雅記,山ノ内祥訓,荒木令江,岩崎未央,杉山直幸,福島敦史,田中聡,五斗進,石濱 泰
    • Organizer
      トーゴーの日シンポジウム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] jPOSTrepoメタデータのSDRF化2021

    • Author(s)
      有馬佳奈美、岡本瑠璃、小林大樹、吉沢明康、河野信
    • Organizer
      トーゴーの日シンポジウム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] An extension of Mass++ ver.4, a data viewer, for proteome analysis2020

    • Author(s)
      Tanaka, S., Murase, M., Kato, M., Tabata, T., Kusano, M., Kawano, S., Goto, S., Ishihama, Y., Yoshizawa, A.C.
    • Organizer
      ASMS 2020 Reboot
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 質量分析インフォマティクスの世界:どこから来て、何者で、どこに向かうのか2020

    • Author(s)
      吉沢 明康
    • Organizer
      第9回生命医薬情報学連合大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Book] 遺伝学の百科事典2022

    • Author(s)
      日本遺伝学会
    • Total Pages
      690
    • Publisher
      丸善出版
    • ISBN
      9784621306604
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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