Statistical method for understanding cancer genome development and pathogenesis

• Project/Area Number: 24700272
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Statistical science
• Research Institution: The University of Tokyo
• Principal Investigator: SHIRAISHI Yuichi 東京大学, 医科学研究所, 助教 (70516880)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: ベイズ統計学 / 次世代シークエンス解析 / 統計数学 / 癌 / ゲノム / がんゲノム / 統計科学

Research Abstract

We developed a novel method, Empirical Bayesian mutation Calling (EBCall) for detecting somatic mutations. Unlike previous methods, the proposed method discriminates somatic mutations from sequencing errors based on an empirical Bayesian framework, where the model parameters are estimated using sequencing data from multiple non-paired normal samples. we demonstrated that our method not only outperforms several existing methods in the calling of mutations with moderate allele frequencies but also enables accurate calling of mutations with low allele frequencies (~10%) harboured within a minor tumour subpopulation, thus allowing for the deciphering of fine substructures within a tumour specimen.

Research Products

• [Journal Article] ACTN1 mutations cause congenital macrothrombocytopenia (2013)
  • Author(s): Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S and Ogawa S.
  • Journal Title: American Journal of Human Genetics Volume: 92(3) Pages: 431-438
• [Journal Article] An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data (2013)
  • Author(s): Shiraishi Y, Sato Y, Chiba K, Okuno Y, Nagata Y, Yoshida K, Shiba N, Hayashi Y, Kume H, Homma Y, Sanada M, Ogawa S and Miyano S.
  • Journal Title: Nucleic Acids Research Volume: 41(7)
• [Journal Article] Integrated molecular analysis of clear-cell renal cell carcinoma (2013)
  • Author(s): Sato Y, Yoshizato T, Shiraishi Y, Maekawa S, Okuno Y, Kamura T, Shimamura T, Sato-Otsubo A, Nagae G, Suzuki H, Nagata Y, Yoshida K, Kon A, Suzuki Y, Chiba K, Tanaka H, Niida A, Fujimoto A, Tsunoda T, Morikawa T, Maeda D, Kume H, Sugano S, Fukayama M, Aburatani H, Sanada M, Miyano S, Homma Y and Ogawa S.
  • Journal Title: Nature Genetics Volume: 45(8) Pages: 860-7
• [Journal Article] Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia (2013)
  • Author(s): Sakaguchi H, Okuno Y, Muramatsu H, Yoshida K, Shiraishi Y, Takahashi M, Kon A, Sanada M, Chiba K, Tanaka H, Makishima H, Wang X, Xu Y, Doisaki S, Hama A, Nakanishi K, Takahashi Y, Yoshida N, Maciejewski JP, Miyano S, Ogawa S and Kojima S.
  • Journal Title: Nature Genetics Volume: 45(8) Pages: 937-41
• [Journal Article] Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms (2013)
  • Author(s): Kon A, Shih LY, Minamino M, Sanada M, Shiraishi Y, Nagata Y, Yoshida K, Okuno Y, Bando M, Nakato R, Ishikawa S, Sato-Otsubo A, Nagae G, Nishimoto A, Haferlach C, Nowak D, Sato Y, Alpermann T, Nagasaki M, Shimamura T, Tanaka H, Chiba K, Yamamoto R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Nakamaki T, Ishiyama K, Nolte F, Hofmann WK, Miyawaki S, Chiba S, Mori H, Nakauchi H, Koeffler HP, Aburatani H, Haferlach T, Shirahige K, Miyano S and Ogawa S.
  • Journal Title: Nature Genetics Volume: 45(10) Pages: 1232-7
• [Journal Article] The landscape of somatic mutations in Down syndrome-related myeloid disorders (2013)
  • Author(s): Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, Sanada M, Park MJ, Terui K, Suzuki H, Kon A, Nagata Y, Sato Y, Wang R, Shiba N, Chiba K, Tanaka H, Hama A, Muramatsu H, Hasegawa D, Nakamura K, Kanegane H, Tsukamoto K, Adachi S, Kawakami K, Kato K, Nishimura R, Izraeli S, Hayashi Y, Miyano S, Kojima S, Ito E, Ogawa S.
  • Journal Title: Nature Genetics Volume: 45(11) Pages: 1293-9
• [Journal Article] An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data (2013)
  • Author(s): Yuichi Shiraishi
  • Journal Title: Nucleic Acid Research Volume: 41 Issue: 7 Pages: e89-e89
  • DOI: 10.1093/nar/gkt126
  • Peer Reviewed
• [Journal Article] Integrated molecular analysis of clear-cell renal cell carcinoma. (2013)
  • Author(s): Sato Y, Yoshida K
  • Journal Title: Nature Genet. Volume: 45 Issue: 8 Pages: 860-867
  • DOI: 10.1038/ng.2699
  • Peer Reviewed
• [Journal Article] The landscape of somatic mutations in Down syndrome-related myeloid disorders. (2013)
  • Author(s): Yoshida K
  • Journal Title: Nature Genet. Volume: 45 Issue: 11 Pages: 1293-1200
  • DOI: 10.1038/ng.2759
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia (2011)
  • Author(s): Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S and Ogawa S.
  • Journal Title: Nature Volume: 478 Pages: 64-69
• [Presentation] An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data (2014)
  • Author(s): Yuichi Shiraishi
  • Organizer: Pacific Symposium on Biocomputing, 2014
  • Place of Presentation: Hawaii, USA
• [Presentation] An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data (2013)
  • Author(s): Yuichi Shiraishi
  • Organizer: Clinical Genomics & Informatics Europe conference & expo, 2013
  • Place of Presentation: Lisbon, Portugal
• [Presentation] Integrated analysis of whole genome and whole transcriptome sequencing of HBV-associated hepatocellular carcinoma (2013)
  • Author(s): Yuichi Shiraishi
  • Organizer: COLD SPRING HARBOR ASIA CONFERENCES Frontiers in Bioinformatics, 2013
  • Place of Presentation: Suzhou, China
  • Invited
• [Presentation] Integrated analysis of whole genome and whole transcriptome sequencing of HBV-associated hepatocellular carcinoma (2013)
  • Author(s): 白石友一
  • Organizer: NGS現場の会、第三回研究会
  • Place of Presentation: 神戸
• [Presentation] Integrated analysis of whole genome and whole transcriptome sequencing of HBV-associated hepatocellular carcinoma (2013)
  • Author(s): Yuichi Shiraishi
  • Organizer: COLD SPRING HARBOR CONFERENCES, The Biology of Genomes, 2013
  • Place of Presentation: COLD SPRING HARBOR, USA
• [Presentation] An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data (2013)
  • Author(s): Yuichi Shiraishi
  • Organizer: Mutation Detection 2013
  • Place of Presentation: Lake Louise, Canada
• [Presentation] An empirical Bayesian framework for mutation detection from cancer genome sequencing data
  • Author(s): Yuichi Shiraishi, Yusuke Sato, Yusuke Okuno, Kenichi Yoshida, Yasunobu Nagata, Masashi Sanda, Seishi Ogawa, Satoru Miyano
  • Organizer: 2012 Sapporo Workshop on Machine Learning and Applications to Biology
  • Place of Presentation: 札幌
  • Invited
• [Presentation] がんの病態，発病機序を理解するためのゲノム解析
  • Author(s): 白石友一
  • Organizer: 第15回情報論的学習理論ワークショップ(IBIS2012)
  • Place of Presentation: 東京
  • Invited
• [Presentation] 第12回日本再生医療学会総会
  • Author(s): 白石友一
  • Organizer: がんゲノムにおける後天的変異を高感度に検出するための統計的手法について
  • Place of Presentation: 横浜
  • Invited
• [Remarks] Genomon-exome
  • URL: http://genomon.hgc.jp/exome/
• [Remarks] Genomon-Fusion
  • URL: http://genomon.hgc.jp/rna/
• [Remarks] Genomon exome
  • URL: http://genomon.hgc.jp/exome/
• [Remarks] Genomon fusion
  • URL: http://genomon.hgc.jp/rna/