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Development of a Mutant Protein Sequence Prediction System for the Realization of Proteogenomics

Research Project

Project/Area Number 21K17850
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionNiigata University

Principal Investigator

LING YIWEI  新潟大学, 医歯学系, 助教 (70804540)

Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsプロテオゲノム / がん変異 / プロテオミクス / 精密医療 / プロテオゲノミクス / 変異タンパク質配列 / 予測システム
Outline of Research at the Start

本研究は、プロテオゲノム解析の視点から出発し、癌ゲノム異常・タンパク質発現異常がどのような形でプロテオームレベルの変化をもたらし、細胞の表現型を規定しているのかについての機序を俯瞰的に描出する事を目的としている。質量分析結果のスペクトルからペプチド配列を推定するために、遺伝子変異を反映させたタンパク配列を予測し、プロテオゲノミクス研究をより正確で精度の高い結果が得られるようにするための仕組みを構築する。これにより、癌の発症メカニズムを検証し、癌患者のタンパク質の変異パターンに基づいて最適な標的治療を選択する事が可能になるための基盤を整備する事が可能になる。

Outline of Final Research Achievements

This study comprehensively analyzed how cancer-related genomic and protein expression abnormalities affect cellular phenotypes from a proteogenomic perspective. We constructed a novel protein sequence database that incorporates genomic mutations, addressing the limitation of conventional proteomic analyses that fail to reflect such mutations. As a result, the accuracy of peptide identification from mass spectrometry data improved, establishing a foundation for elucidating cancer pathogenesis and enabling optimized targeted therapies. Part of the results has been presented at domestic and international conferences.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ゲノム変異情報に基づいた変異タンパク質配列の網羅的予測システムを開発し、プロテオゲノミクス解析の精度と信頼性を飛躍的に向上させるものである。これにより、従来の手法では検出困難だったがん関連タンパク質の異常を明らかにし、発がんメカニズムの理解を深化させるとともに、個別化医療における最適な標的治療選択の基盤を提供する。広範な疾患研究への応用も期待され、社会的インパクトは大きい。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (34 results)

All 2024 2023 2022 2021 Other

All Journal Article (21 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mucin phenotype and genetic alterations in non-V600E BRAF-mutated colorectal cancer2024

    • Author(s)
      Ozeki Hikaru、Shimada Yoshifumi、Nakano Mae、Kondo Shuhei、Ohashi Riuko、Miwa Yamato、Yamai Daisuke、Matsumoto Akio、Abe Kaoru、Tajima Yosuke、Ichikawa Hiroshi、Sakata Jun、Takii Yasumasa、Sugai Mika、Nagai Takahiro、Ling Yiwei、Okuda Shujiro、Wakai Toshifumi
    • Journal Title

      Human Pathology

      Volume: 145 Pages: 71-79

    • DOI

      10.1016/j.humpath.2024.02.009

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathological and biological significance of the specific glycan, TRA-1-60, on aggressive gastric adenocarcinoma2024

    • Author(s)
      Ayaka Mitsui, Hidekazu Iioka, Yiwei Ling, Shujiro Okuda, Akira Kurose, Michael Schopperle, Tomoko Kondo, Masakiyo Sakaguchi, Ken Saito, Eisaku Kondo
    • Journal Title

      Laboratory Investigation

      Volume: 104 Issue: 7 Pages: 102073-102073

    • DOI

      10.1016/j.labinv.2024.102073

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients2023

    • Author(s)
      Nagahashi M, Ling Y, Toshikawa C, Hayashida T, Kitagawa Y, Futamura M, Kuwayama T, Nakamura S, Yamauchi H, Yamauchi T, Kaneko K, Kanbayashi C, Sato N, Tsuchida J, Moro K, Nakajima M, Shimada Y, Ichikawa H, Lyle S, Miyoshi Y, Takabe K, Okuda S, Wakai T.
    • Journal Title

      Breast Cancer

      Volume: - Issue: 4 Pages: 584-595

    • DOI

      10.1007/s12282-023-01449-2

    • Related Report
      2024 Annual Research Report 2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical significance of metastatic tumor deposit foci in rectal cancer in the lateral pelvic lymph node area2023

    • Author(s)
      Yamai Daisuke、Shimada Yoshifumi、Nakano Masato、Ozeki Hikaru、Matsumoto Akio、Abe Kaoru、Tajima Yosuke、Nakano Mae、Ichikawa Hiroshi、Sakata Jun、Nagai Takahiro、Ling Yiwei、Okuda Shujiro、Watanabe Gen、Nogami Hitoshi、Maruyama Satoshi、Takii Yasumasa、Wakai Toshifumi
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 28 Issue: 10 Pages: 1388-1397

    • DOI

      10.1007/s10147-023-02391-1

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NKp44-based chimeric antigen receptor effectively redirects primary T cells against synovial sarcoma2023

    • Author(s)
      Yudai Murayama, Yasushi Kasahara, Nobuhiro Kubo, Chansu Shin, Masaru Imamura, Naoki Oike, Takashi Ariizumi, Akihiko Saitoh, Minori Baba, Tomohiro Miyazaki, Yuko Suzuki, Yiwei Ling, Shujiro Okuda, Keichiro Mihara, Akira Ogose, Hiroyuki Kawashima, Chihaya Imai
    • Journal Title

      Transl Oncol

      Volume: ahead Pages: 1-1

    • DOI

      10.1016/j.tranon.2022.101521

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans2023

    • Author(s)
      Kazuki Natsui, Atsunori Tsuchiya, Risa Imamiya, Mayuko Osada, Yui Ishii, Yohei Koseki, Nobutaka Takeda, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Riuko Ohashi, Yiwei Ling, Koji Ueda, Nobuko Moritoki, Kazuhiro Sato, Takahiro Nakajima, Yoshinori Hasegawa, Shujiro Okuda, Shinsuke Shibata, Shuji Terai
    • Journal Title

      Liver Int

      Volume: 43(5) Issue: 5 Pages: 1126-1140

    • DOI

      10.1111/liv.15539

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 連載 バイオインフォマティクスの世界・第18回(最終回) プレシジョン・メディシンⅡ2022

    • Author(s)
      凌 一葦
    • Journal Title

      医学のあゆみ

      Volume: 282 Issue: 11 Pages: 1017-1022

    • DOI

      10.32118/ayu282111017

    • ISSN
      0039-2359
    • Year and Date
      2022-09-10
    • Related Report
      2024 Annual Research Report
  • [Journal Article] 連載 バイオインフォマティクスの世界・第17回 プレシジョン・メディシンⅠ2022

    • Author(s)
      凌 一葦
    • Journal Title

      医学のあゆみ

      Volume: 282 Issue: 9 Pages: 837-842

    • DOI

      10.32118/ayu28209837

    • ISSN
      0039-2359
    • Year and Date
      2022-08-27
    • Related Report
      2024 Annual Research Report
  • [Journal Article] Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia2022

    • Author(s)
      Shimada Y, Nakano M, Mizuno KI, Yokoyama J, Matsumoto A, Tanaka K, Oyanagi H, Nakano M, Hirose Y, Ichikawa H, Sakata J, Kameyama H, Takii Y, Sugai M, Ling Y, Takeuchi S, Okuda S, Terai S, Ajioka Y, Wakai T.
    • Journal Title

      Oncology Letters

      Volume: 24 Issue: 6 Pages: 442-442

    • DOI

      10.3892/ol.2022.13562

    • Related Report
      2024 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of <i>Atg2b</i> and <i>Gskip</i> Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size2022

    • Author(s)
      Sakai Shun-suke、Hasegawa Atsushi、Ishimura Ryosuke、Tamura Naoki、Kageyama Shun、Komatsu-Hirota Satoko、Abe Manabu、Ling Yiwei、Okuda Shujiro、Funayama Manabu、Kikkawa Mika、Miura Yoshiki、Sakimura Kenji、Narita Ichiei、Waguri Satoshi、Shimizu Ritsuko、Komatsu Masaaki
    • Journal Title

      Molecular and Cellular Biology

      Volume: 42 Issue: 1 Pages: 1-17

    • DOI

      10.1128/mcb.00024-21

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Putrescine Production by Latilactobacillus curvatus KP 3-4 Isolated from Fermented Foods2022

    • Author(s)
      Hirano Rika、Kume Aiko、Nishiyama Chisato、Honda Ryosuke、Shirasawa Hideto、Ling Yiwei、Sugiyama Yuta、Nara Misaki、Shimokawa Hiromi、Kawada Hiroki、Koyanagi Takashi、Ashida Hisashi、Okuda Shujiro、Matsumoto Mitsuharu、Takagi Hiroki、Kurihara Shin
    • Journal Title

      Microorganisms

      Volume: 10 Issue: 4 Pages: 697-697

    • DOI

      10.3390/microorganisms10040697

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unveiling microbiome profiles in human inner body fluids and tumor tissues with pancreatic or biliary tract cancer.2022

    • Author(s)
      Okuda S, Hirose Y, Takihara H, Okuda A, Ling Y, Tajima Y, Shimada Y, Ichikawa H, Takizawa K, Sakata J, Wakai T.
    • Journal Title

      Sci Rep.

      Volume: 12(1) Issue: 1 Pages: 8766-8766

    • DOI

      10.1038/s41598-022-12658-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] やってみようバイオインフォマティクス: エンリッチメント解析編2022

    • Author(s)
      凌 一葦、永井貴大、奥田修二郎
    • Journal Title

      医学のあゆみ

      Volume: 282(7,8) Pages: 767-774

    • Related Report
      2022 Research-status Report
  • [Journal Article] やってみようバイオインフォマティクス: RNA-seq解析編2022

    • Author(s)
      永井貴大、凌 一葦、奥田修二郎
    • Journal Title

      医学のあゆみ

      Volume: 282(3) Pages: 228-235

    • Related Report
      2022 Research-status Report
  • [Journal Article] やってみようバイオインフォマティクス: SNP解析編2022

    • Author(s)
      永井貴大、凌 一葦、奥田修二郎
    • Journal Title

      医学のあゆみ

      Volume: 282(2) Pages: 158-168

    • Related Report
      2022 Research-status Report
  • [Journal Article] プレシジョン・メディシンI: がんゲノム医療2022

    • Author(s)
      凌一葦
    • Journal Title

      医学のあゆみ

      Volume: 282(9) Pages: 837-849

    • Related Report
      2022 Research-status Report
  • [Journal Article] プレシジョン・メディシンII: がんゲノミクスの応用2022

    • Author(s)
      凌一葦
    • Journal Title

      医学のあゆみ

      Volume: 282(11) Pages: 1017-1020

    • Related Report
      2022 Research-status Report
  • [Journal Article] Unveiling microbiome profiles in human inner body fluids and tumor tissues with pancreatic or biliary tract cancer2022

    • Author(s)
      Shujiro Okuda, Yuki Hirose, Hayato Takihara, Akiko Okuda, Yiwei Ling, Yosuke Tajima, Yoshifumi Shimada, Hiroshi Ichikawa, Kazuyasu Takizawa, Jun Sakata, Toshifumi Wakai
    • Journal Title

      Scientific Reports

      Volume: 0 Pages: 0-0

    • Related Report
      2021 Research-status Report
    • Open Access
  • [Journal Article] Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer2021

    • Author(s)
      Ikarashi Mayuko、Tsuchida Junko、Nagahashi Masayuki、Takeuchi Shiho、Moro Kazuki、Toshikawa Chie、Abe Shun、Ichikawa Hiroshi、Shimada Yoshifumi、Sakata Jun、Koyama Yu、Sato Nobuaki、Hait Nitai C.、Ling Yiwei、Okuda Shujiro、Takabe Kazuaki、Wakai Toshifumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 24 Pages: 13367-13367

    • DOI

      10.3390/ijms222413367

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer.2021

    • Author(s)
      Okuda S, Shimada Y, Tajima Y, Yuza K, Hirose Y, Ichikawa H, Nagahashi M, Sakata J, Ling Y, Miura N, Sugai M, Watanabe Y, Takeuchi S, Wakai T
    • Journal Title

      Comput Struct Biotechnol J

      Volume: 19 Pages: 3330-3338

    • DOI

      10.1016/j.csbj.2021.05.049

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological characteristics and artificial intelligence for predicting tumor mutational burden-high colorectal cancer2021

    • Author(s)
      Shimada Yoshifumi、Okuda Shujiro、Watanabe Yu、Tajima Yosuke、Nagahashi Masayuki、Ichikawa Hiroshi、Nakano Masato、Sakata Jun、Takii Yasumasa、Kawasaki Takashi、Homma Kei-ichi、Kamori Tomohiro、Oki Eiji、Ling Yiwei、Takeuchi Shiho、Wakai Toshifumi
    • Journal Title

      Journal of Gastroenterology

      Volume: - Issue: 6 Pages: 547-559

    • DOI

      10.1007/s00535-021-01789-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 癌研究と個別化医療におけるバイオインフォマティクスの応用と展望2024

    • Author(s)
      凌一葦
    • Organizer
      第35回日本臨床口腔病理学会総会・学術集会若手の集い
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 精密医療実現に向けたオミクス解析の利活用2024

    • Author(s)
      凌一葦
    • Organizer
      第11回生命医薬情報学連合大会(IIBMP2022)
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] A Novel Approach to Construct Variant Protein Sequences for Precision Medical Proteogenomics2024

    • Author(s)
      Ling Yiwei, Okuda Shujiro
    • Organizer
      HUPO2022
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] プロテオゲノミクスにおける精密医療実現のため、変異タンパク質シーケンス作成アプローチの構築2024

    • Author(s)
      凌一葦、姜瀚、奥田修二郎
    • Organizer
      第46回日本分子生物学会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 遺伝子変異がプロテオームに及ぼす影響を検証するための変異タンパク質配列アプローチの構築と質量分析データ解析2024

    • Author(s)
      姜瀚、奥田修二郎、凌一葦
    • Organizer
      第97回日本生化学会大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] プロテオゲノミクスにおける精密医療実現のため、変異タンパク質シーケンス作成アプローチの構築2023

    • Author(s)
      凌 一葦、 姜瀚、奥田修二郎
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Research-status Report
  • [Presentation] Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients2022

    • Author(s)
      M Nagahashi, C Toshikawa, Y Ling, T Hayashida, Y Kitagawa, M Futamura, K Yoshida, T Kuwayama, S Nakamura, H Yamauchi, T Yamauchi, K Kaneko, C Kanbayashi, N Sato, J Tsuchida, M Nakajima, Y Shimada, H Ichikawa, S Lyle, Y Miyoshi, K Takabe, S Okuda, T Wakai
    • Organizer
      San Antonio Breast Cancer Symposium 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Novel Approach to Construct Variant Protein Sequences for Precision Medical Proteogenomics2022

    • Author(s)
      Yiwei Ling, Shujiro Okuda
    • Organizer
      HUPO2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 緑内障患者のQOVスコアに影響を与える視野領域の検討2022

    • Author(s)
      飯川龍、凌一葦、奥田修二郎、赤木忠道、坂上悠太、五十嵐遼子、有松真央、宮島誠、福地健郎
    • Organizer
      第130回新潟眼科集談会
    • Related Report
      2022 Research-status Report
  • [Presentation] 精密医療実現に向けたオミクス解析の利活用2022

    • Author(s)
      凌一葦
    • Organizer
      2022年日本バイオインフォマティクス学会年会 第 回 生命医薬情報学連合大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 大腸癌における宿主の遺伝子変異と腫瘍内細菌叢のプロファイリング2021

    • Author(s)
      若井俊文, 奥田修二郎, 島田能史, 田島陽介, 廣瀬雄己, 市川寛, 凌一葦, 三浦信明, 須貝美佳, 渡辺由, 竹内志穂, 坂田純
    • Organizer
      第32回日本消化器癌発生学会総会
    • Related Report
      2021 Research-status Report
  • [Remarks] メディカルAIセンター / バイオインフォマティクス分野

    • URL

      https://bioinfo.med.niigata-u.ac.jp

    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] トリプルネガティブ乳癌の予後を診断する方法2022

    • Inventor(s)
      永橋昌幸、奥田修二郎、凌 一葦、若井俊文、利川千絵、兒玉啓輔
    • Industrial Property Rights Holder
      永橋昌幸、奥田修二郎、凌 一葦、若井俊文、利川千絵、兒玉啓輔
    • Industrial Property Rights Type
      特許
    • Patent Publication Number
      2023-111030
    • Filing Date
      2022
    • Acquisition Date
      2024
    • Related Report
      2024 Annual Research Report 2023 Research-status Report

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Published: 2021-04-28   Modified: 2026-01-16  

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