Statistical method for understanding cancer genome development and pathogenesis

2013 Fiscal Year Final Research Report

• 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
• Keywords: ベイズ統計学 / 次世代シークエンス解析

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: pp. 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) Pages: e89
• [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: pp.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: pp.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: pp.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: pp.1293-9
• [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: pp.64-69
• [Remarks] Genomon-exome
  • URL: http://genomon.hgc.jp/exome/
• [Remarks] Genomon-Fusion
  • URL: http://genomon.hgc.jp/rna/