Developing analysis tools of massively parallel cancer evolution simulation to understand intratumor heterogeneity

• Project/Area Number: 17K12773
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Life / Health / Medical informatics
• Research Institution: The University of Tokyo
• Principal Investigator: Niida Atsushi 東京大学, 医科学研究所, 助教 (00772493)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シミュレーション / がん / 進化 / スーパーコンピュータ / 可視化 / 癌

Outline of Final Research Achievements

Cancer is caused by an evolutionary process where a normal cell acquires mutations and is subject to natural selection. To understand the evolutionary process, we have performed a series of studies by employing cancer evolution simulation. In this study we developed a novel tools for sensitivity analysis, which examines how parameter values affect evolutionary dynamics. the novel tool, MASSIVE first performs massively parallel simulations on a super computer and then examines the results by an interactive visualization tool, MASSIVE viewer. As an example of an application of MASSIVE, we analyzed cancer evolution simulation on a dimensional lattice and found that spatial resource bias prompts branching evolution.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した新しいパラメータ感受性解析手法 MASSIVEはこれまでの感受性解析手法とは全く異なる超並列計算と対話的可視化という二つの計算科学的技術を組み合わせ、幅広いパラメータ空間を直感的に探索可能にした点に新規性がある。我々はがんの進化シミュレーションの解析を目的に開発を行っているが、シミュレーション一般に応用可能な技術であり、感受性解析のデファクトスタンダードになると期待される。

Research Products

• [Journal Article] Sensitivity analysis of agent-based simulation utilizing massively parallel computation and interactive data visualization (2019)
  • Author(s): Niida A, Hasegawa T, Miyano S
  • Journal Title: PLoS One Volume: 14(3) Issue: 3 Pages: e0210678-e0210678
  • DOI: 10.1371/journal.pone.0210678
  • Peer Reviewed / Open Access
• [Journal Article] Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer (2018)
  • Author(s): Sakai, E., Nakayama, M., Oshima, H., Kouyama, Y., Niida, A., Fujii, S., Ochiai, A., Nakayama, K. I., Mimori, K., Suzuki, Y., Hong, C. P., Ock, C. Y., Kim, S. J. and Oshima, M.
  • Journal Title: Cancer reserach Volume: in press
  • NAID: 120006452378
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling (2018)
  • Author(s): Niida Atsushi、Nagayama Satoshi、Miyano Satoru、Mimori Koshi
  • Journal Title: Cancer science Volume: 109 Issue: 4 Pages: 884-892
  • DOI: 10.1111/cas.13510
  • Peer Reviewed / Open Access
• [Journal Article] Impediment of Replication Forks by Long Non-coding RNA Provokes Chromosomal Rearrangements by Error-Prone Restart (2017)
  • Author(s): Watanabe Takaaki、Marotta Michael、Suzuki Ryusuke、Diede Scott J.、Tapscott Stephen J.、Niida Atsushi、Chen Xiongfong、Mouakkad Lila、Kondratova Anna、Giuliano Armando E.、Orsulic Sandra、Tanaka Hisashi
  • Journal Title: Cell report Volume: 21 Issue: 8 Pages: 2223-2235
  • DOI: 10.1016/j.celrep.2017.10.103
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14. (2017)
  • Author(s): Takahashi Y, Sugimachi K, Yamamoto K, Niida A, Shimamura T, Sato T, Watanabe M, Tanaka J, Kudo S, Sugihara K, Hase K, Kusunoki M, Yamada K, Shimada Y, Moriya Y, Suzuki Y, Miyano S, Mori M, Mimori K
  • Journal Title: Cancer Sci. Volume: 108(11) Issue: 11 Pages: 2239-2247
  • DOI: 10.1111/cas.13391
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Multiregional sequencing unveiled temporal dynamics of intratumor heterogeneity during colorectal cancer evolution (2017)
  • Author(s): Atsuahi Niida
  • Organizer: International Conference on Translational Cancer Medicine held in cooperation with the Latin American Cooperative Oncology Group (LACOG)
  • Int'l Joint Research
• [Presentation] がんの進化シミュレーション (2017)
  • Author(s): 新井田厚司
  • Organizer: 第6回生命医薬情報学連合大会
• [Presentation] 大腸がんの進化と腫瘍内不均一性 (2017)
  • Author(s): 新井田厚司
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Remarks] MASSIVE viewer
  • URL: https://www.hgc.jp/~niiyan/massive/