Analysis of genetic variation in repetitive and non-reference genomic regions

• Project/Area Number: 26430196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Kyoto University (2016); Institute of Physical and Chemical Research (2014-2015)
• Principal Investigator: Fujimoto Akihiro 京都大学, 医学研究科, 特定准教授 (30525853)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 次世代シークエンサー / ヒトゲノム多様性 / 第３世代シークエンサー / 解析困難領域 / 全ゲノムシークエンス

Outline of Final Research Achievements

Recent progress of DNA sequencing technology enables us to sequence whole genome. However, read length of the current DNA sequencers are short, and therefore repetitive regions and non-reference genomic regions can not be analyzed. To examine the polymorphism of repetitive regions and non-reference genomic regions, we collected unmapped reads from human whole genome sequence data, and designed capture probes to obtain DNA from these regions. We sequenced the collected DNA with a long read sequencing technology. We identified genetic variation in the repetitive and non-reference genomic regions.

Research Products

• [Journal Article] Whole genome sequencing discriminates hepatocellular carcinoma with intrahepatic metastasis from multi-centric tumors (2017)
  • Author(s): Furuta M, Ueno M, Fujimoto A, Hayami S, Yasukawa S, Kojima F, Arihiro K, Kawakami Y, Wardell CP, Shiraishi Y, Tanaka H, Nakano K, Maejima K, Sasaki-Oku A, Tokunaga N, Boroevich KA, Abe T, Aikata H, Ohdan H, Gotoh K, Kubo M, Tsunoda T, Miyano S, Chayama K, Yamaue H, Nakagawa H
  • Journal Title: J Hepatol Volume: 66(2) Issue: 2 Pages: 363-373
  • DOI: 10.1016/j.jhep.2016.09.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutational signatures associated with tobacco smoking in human cancer. (2016)
  • Author(s): Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I, Nik-Zainal S, Totoki Y, Fujimoto A, Nakagawa H, Shibata T, Campbell PJ, Vineis P, Phillips DH, Stratton MR.
  • Journal Title: Science Volume: 354 Issue: 6312 Pages: 618-622
  • DOI: 10.1126/science.aag0299
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes (2016)
  • Author(s): Fujimoto A, Okada Y, Boroevich KA, Tsunoda T, Taniguchi H, Nakagawa H
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 26483-26483
  • DOI: 10.1038/srep26483
  • NAID: 120005774574
  • Peer Reviewed / Open Access
• [Journal Article] Whole genome mutational landscape and characterization of non-coding and structural mutations in liver cancer. (2016)
  • Author(s): Fujimoto A et al.
  • Journal Title: Nat Genet Volume: 48 Issue: 5 Pages: 500-509
  • DOI: 10.1038/ng.3547
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A comprehensive assessment of somatic mutation detection in cancer using whole genome sequencing. (2015)
  • Author(s): Alioto TS...,, Fujimoto et al
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 10001-10001
  • DOI: 10.1038/ncomms10001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Circulating tumor DNA analysis for liver cancers and its usefulness as a liquid biopsy. (2015)
  • Author(s): Ono A, Fujimoto A, Yamamoto Y, Akamatsu S, Nobuhiko H, Imamura M, Kawaoka T, Tsuge M, Abe H, Hayes CN, Miki D, Furuta M, Tsunoda T, Miyano S, Kubo M, Aikata H, Ochi H, Kawakami Y, Arihiro K, Ohdan H, Nakagawa H, Chayama K
  • Journal Title: Cellular and Molecular Gastroenterology and Hepatology Volume: 1 Issue: 5 Pages: 516-534
  • DOI: 10.1016/j.jcmgh.2015.06.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes. (2015)
  • Author(s): Shigemizu D, Aiba T, Nakagawa H, Ozaki K, Miya F, Satake W, Toda T, Miyamoto Y, Fujimoto A, Suzuki Y, Kubo M, Tsunoda T, Shimizu W, Tanaka T.
  • Journal Title: PLoS One. Volume: 10 (7) Issue: 7 Pages: e0130329-e0130329
  • DOI: 10.1371/journal.pone.0130329
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cancer whole-genome sequencing: present and future (2015)
  • Author(s): Nakagawa H, Wardell CP , Furuta M, Taniguchi H, Fujimoto A
  • Journal Title: Oncogene Volume: AOP Issue: 49 Pages: 1-8
  • DOI: 10.1038/onc.2015.90
  • Peer Reviewed / Open Access
• [Journal Article] Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity (2015)
  • Author(s): Fujimoto A, Furuta M, Shiraishi Y, Shigemizu D, Abe T, Boroevich KA, Nakano K, Yamamoto Y, Tanaka H, Shibuya T, Shibata T, Kubo M, Chayama K, Miyano S, Tsunoda T, Nakagawa H, 他
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6120-6120
  • DOI: 10.1038/ncomms7120
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers (2014)
  • Author(s): Shiraishi Y, Fujimoto A, Furuta M, Chayama K, Tsunoda T, Miyano S, and Nakagawa H, 他
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e114263-e114263
  • DOI: 10.1371/journal.pone.0114263
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Correspondence: Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan (2014)
  • Author(s): Takezawa, Y., Kato, K., Oota. H., Caulfield, T., Fujimoto, A., Honda, F., Kamatani, N., Kawamura, S., Kawashima, K., Kimura, R., Matsumae, H., Saito, A., Savage, P. E., Seguchi, N., Shimizu, K., Terao, S., Yamaguchi-Kabata, Y., Yasukouchi, A., Yoneda, M. and Tokunaga, K.
  • Journal Title: BMC Medical Ethics Volume: 15 Issue: 1 Pages: 33-33
  • DOI: 10.1186/1472-6939-15-33
  • Peer Reviewed / Open Access
• [Journal Article] 肝癌のゲノム解析と発癌メカニズムの解明 (2014)
  • Author(s): 藤本明洋, 中川 英刀
  • Journal Title: Medical Science Digest Volume: 11月号
• [Journal Article] がんのゲノム解析 (2014)
  • Author(s): 藤本明洋
  • Journal Title: 血管医学 Volume: 9月号
• [Journal Article] 肝がんの網羅的ゲノム解析 (2014)
  • Author(s): 藤本明洋, 角田達彦, 中川英刀
  • Journal Title: 医学のあゆみ Volume: 6月7日号
• [Journal Article] 全ゲノムシークエンス (2014)
  • Author(s): 藤本明洋
  • Journal Title: 医学のあゆみ Volume: 5月3日号
• [Journal Article] 毛髪の太さと関連するEDAR遺伝子多型――集団間分化と毛髪形態の進化史 (2014)
  • Author(s): 藤本明洋
  • Journal Title: 医学のあゆみ Volume: 4月26日号
• [Journal Article] 次世代シークエンサーを用いた遺伝的多様性の包括的解析とゲノム人類学への応用 (2014)
  • Author(s): 藤本明洋
  • Journal Title: 医学のあゆみ Volume: 3月22日号
• [Journal Article] 肝腫瘍の全ゲノム解析 (2014)
  • Author(s): 藤本明洋, 角田達彦, 中川英刀
  • Journal Title: 肝胆膵 Volume: 2014年3月号
• [Presentation] Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer (2016)
  • Author(s): 藤本明洋
  • Organizer: 66th Annual ASHG Meeting
  • Place of Presentation: カナダ バンクーバー
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer (2016)
  • Author(s): 藤本明洋
  • Organizer: 第75回日本癌学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer (2016)
  • Author(s): 藤本明洋
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Invited
• [Presentation] Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer (2016)
  • Author(s): 藤本明洋
  • Organizer: 群馬大学 第三回未来先端研究機構国際シンポジウム
  • Place of Presentation: 群馬県 高崎市
  • Int'l Joint Research / Invited
• [Presentation] Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer (2016)
  • Author(s): 藤本明洋
  • Organizer: National Cheng Kung University Taiwan International Conference
  • Place of Presentation: 台湾台南市
• [Presentation] 次世代シークエンサーの情報解析 (2015)
  • Author(s): 藤本明洋
  • Organizer: 日本人類遺伝学会 第60回大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-17
  • Invited
• [Presentation] Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes. (2015)
  • Author(s): 藤本明洋
  • Organizer: ASHG 2016 Annual Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-10-10
  • Int'l Joint Research
• [Presentation] 次世代シークエンスデータの解析によるマイクロサテライト変異の検出 (2014)
  • Author(s): 藤本明洋、松原長秀、佐々木亜弥、古田繭子、阿部哲雄、角田逹彦、冨田尚裕、中川英刀
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: タワーホール船堀（東京都）
  • Year and Date: 2014-11-22
• [Presentation] Whole genome sequence analysis of liver cancers reveals driver events and impact of chronic inflammation (2014)
  • Author(s): Akihiro Fujimoto, Mayuko Furuta, Yuichi Shiraishi, Kunihito Gotoh, Masakazu Yamamoto, Toru Nakamura, Hiroki Yamaue, Kazuaki Chayama, Satoru Miyano, Tatsuhiko Tsunoda, Hidewaki Nakagawa
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] 次世代シークエンスデータの解析によるマイクロサテライト変異の検出 (2014)
  • Author(s): 藤本明洋、松原長秀、佐々木亜弥、古田繭子、阿部哲雄、角田逹彦、冨田尚裕、中川英刀
  • Organizer: 日本遺伝学会
  • Place of Presentation: 長浜バイオ大学（滋賀県）
  • Year and Date: 2014-09-18
• [Remarks] 藤本明洋のページ 発表論文
  • URL: https://sites.google.com/site/fujimotoakihironopeji/home/fa-biao-lun-wen
• [Remarks] 慢性肝炎や肝硬変は肝内胆管がんのゲノム異常と発生に強く関与
  • URL: http://www.riken.jp/pr/press/2015/20150130_3/