Statistical Modeling Methodology on Boolean Functions for Conquering Cancer Complex Ecosystem

• Project/Area Number: 18K18151
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Nagoya University
• Principal Investigator: Matsui Yusuke 名古屋大学, 医学系研究科(保健), 准教授 (90761495)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: がんサブクローン進化 / Cancer hallmark / タンパク質複合体 / 共発現変動 / 擬似時間推定 / 次元縮小法 / 共発現変動解析 / コピュラ / がん / がんの進化 / 多領域シークエンシグ / プロテオゲノム解析 / 生命情報学 / バイオインフォマティクス / 不均一性 / 統計科学 / がん進化 / 生体生命情報学

Outline of Final Research Achievements

We have developed two main algorithms to approach the complex ecosystem of cancer. One is the estimation algorithm for cancer evolutionary structure at the pathway level using causal inference, and the other is a prediction algorithm for the causal factor causing protein complex deregulation and an approach for estimating mutation effects. These were applied to actual large-scale cancer omics cohort data to confirm their usefulness.

Academic Significance and Societal Importance of the Research Achievements

がんの進展に関わる複雑な生物学的現象を数理的にモデリングしていくことで、網羅的な解析のみでは理解できないがんシステムの複雑性を理解でき、がんのフェノタイプを規定する原因同定や薬剤候補スクリーニングへの応用が期待できる。

Research Products

• [Journal Article] Meta-analysis integrated with multi-omics data analysis to elucidate pathogenic mechanisms of age-related knee osteoarthritis in mice (2022)
  • Author(s): Iijima Hirotaka、Gilmer Gabrielle、Wang Kai、Sivakumar Sruthi、Evans Christopher、Matsui Yusuke、Ambrosio Fabrisia
  • Journal Title: The Journals of Gerontology: Series A Volume: glab386 Issue: 7 Pages: 1321-1334
  • DOI: 10.1093/gerona/glab386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin. (2021)
  • Author(s): Shimizu D, Taniue K, Matsui Y, Haeno H, Araki H, Miura F, Fukunaga M, Shiraishi K, Miyamoto Y, Tsukamoto S, Komine A, Kobayashi Y, Kitagawa A, Yoshikawa Y, Sato K, Saito T, Ito S, Masuda T, Niida A, Suzuki M, Baba H, Ito T, Akimitsu N, Kodera Y, Mimori K.
  • Journal Title: Cancer Gene Ther. Volume: Epub Issue: 5 Pages: 1-1
  • DOI: 10.1038/s41417-021-00401-w
  • Peer Reviewed / Open Access
• [Journal Article] Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents (2021)
  • Author(s): Komura Kazumasa、Inamoto Teruo、Tsujino Takuya、Matsui Yusuke et al.
  • Journal Title: Oncogene Volume: 40 Issue: 43 Pages: 6210-6222
  • DOI: 10.1038/s41388-021-02021-y
  • Peer Reviewed / Open Access
• [Journal Article] RoDiCE: robust differential protein co-expression analysis for cancer complexome (2021)
  • Author(s): Matsui Yusuke、Abe Yuichi、Uno Kohei、Miyano Satoru
  • Journal Title: Bioinformatics Volume: 38 Issue: 5 Pages: 1269-1276
  • DOI: 10.1093/bioinformatics/btab612
  • Peer Reviewed
• [Journal Article] Pre-stimulus alpha oscillation and post-stimulus cortical activity differ in localization between consciously perceived and missed near-threshold somatosensory stimuli (2021)
  • Author(s): Uemura Jun-ichi, Hoshino Aiko, Igarashi Go, Matsui Yusuke, Chishima Makoto, Hoshiyama Minoru
  • Journal Title: EUROPEAN JOURNAL OF NEUROSCIENCE Volume: 54 Issue: 4 Pages: 5518-5530
  • DOI: 10.1111/ejn.15388
  • Peer Reviewed / Open Access
• [Journal Article] Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis (2021)
  • Author(s): Iijima Hirotaka、Gilmer Gabrielle、Wang Kai、Sivakumar Sruthi、Evans Christopher、Matsui Yusuke、Ambrosio Fabrisia
  • Journal Title: bioRxive Volume: 0 Pages: 0-0
  • DOI: 10.1101/2021.05.06.442993
  • Open Access
• [Journal Article] RoDiCE: Robust differential protein co-expression analysis for cancer complexome (2020)
  • Author(s): Matsui Yusuke、Abe Yuichi、Uno Kohei、Miyano Satoru
  • Journal Title: bioRxive Volume: 0 Pages: 0-0
  • DOI: 10.1101/2020.12.22.423973
  • Open Access
• [Journal Article] Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas (2019)
  • Author(s): Ohka Fumiharu、Shinjo Keiko、Deguchi Shoichi、Matsui Yusuke et al.
  • Journal Title: Cancer Research Volume: 79 Issue: 19 Pages: 4814-4827
  • DOI: 10.1158/0008-5472.can-19-1272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Network of Networks Approach for Modeling Interconnected Brain Tissue-Specific Networks. (2019)
  • Author(s): Kawakubo H, Matsui Y, Kushima I, Ozaki N, Shimamura T.
  • Journal Title: Bioinformatics Volume: - Issue: 17 Pages: 1-10
  • DOI: 10.1093/bioinformatics/btz032
  • Peer Reviewed / Open Access
• [Journal Article] Tumor subclonal progression model for cancer hallmark acquisition (2019)
  • Author(s): Matsu Y, Miyano S, Shimamura T
  • Journal Title: LNBI Volume: 10834 Pages: 115-123
  • DOI: 10.1007/978-3-030-14160-8_12
  • ISBN: 9783030141592, 9783030141608
  • Peer Reviewed / Open Access
• [Journal Article] GIMLET: Identifying biological modulators in context-specific gene regulation using local energy statistics (2019)
  • Author(s): Shimamura T, Matsui Y, Kajino T, Ito S, Takahashi T, Miyano S
  • Journal Title: LNBI Volume: 10834 Pages: 124-137
  • DOI: 10.1007/978-3-030-14160-8_13
  • ISBN: 9783030141592, 9783030141608
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Cardiomyocyte-Fated Progenitors from Human-Induced Pluripotent Stem Cells Marked with CD82 (2018)
  • Author(s): Takeda Masafumi、Kanki Yasuharu、Masumoto Hidetoshi、Funakoshi Shunsuke、Hatani Takeshi、Fukushima Hiroyuki、Izumi-Taguchi Akashi、Matsui Yusuke、Shimamura Teppei、Yoshida Yoshinori、Yamashita Jun K.
  • Journal Title: Cell Reports Volume: 22 Issue: 2 Pages: 546-556
  • DOI: 10.1016/j.celrep.2017.12.057
  • NAID: 120006460050
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] DX時代における理学療法学 - データ科学との融合へ向けて - (2021)
  • Author(s): 松井佑介
  • Organizer: 第26回日本基礎理学療法学会学術大会
  • Invited
• [Presentation] 大規模プロテオゲノミクスにおける数理解析アプローチ - cancer complexomeを例として – (2021)
  • Author(s): 松井佑介
  • Organizer: 第72回日本電気泳動学会総会
  • Invited
• [Presentation] 個々のゲノム情報を考慮した変異ペプチドに基づく異常タンパク質の同定方法とアルツハイマー病への応用 (2021)
  • Author(s): 都築凛華、宇野光平、松井佑介
  • Organizer: 2021年度日本分類学会シンポジウム
• [Presentation] アルツハイマー病サブタイプにおけるデータ駆動型アプローチによる空間的バイオマーカー分布構造の検討 (2021)
  • Author(s): 山村柊平、宇野光平、松井佑介
  • Organizer: 第26回日本基礎理学療法学会学術大会
• [Presentation] アルツハイマー病の潜在的病態進行度を推定するための機械学習アプローチの検討 (2021)
  • Author(s): 林勇作、宇野光平、松井佑介
  • Organizer: 第26回日本基礎理学療法学会学術大会
• [Presentation] Toward Achieving Precision Health Driven by Biomedical Informatics with Data Science (2019)
  • Author(s): Yusuke Matsui
  • Organizer: Data Science, Statistics and Visualization 2019
  • Int'l Joint Research / Invited
• [Presentation] 確率生成モデルを用いたRNA-seqデータの解析 (2019)
  • Author(s): 松井佑介
  • Organizer: 統計関連学会連合大会2019
  • Invited