Development of a statistical approach to decipher information from high-order chromatin structure and the epigenome

• Project/Area Number: 25730173
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Life / Health / Medical informatics
• Research Institution: Nagoya University (2014-2015); The University of Tokyo (2013)
• Principal Investigator: Shimamura Teppei 名古屋大学, 医学(系)研究科(研究院), 特任准教授 (00623943)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: バイオインフォマティクス / ベイズモデル / 次世代シークエンサー / 高次クロマチン構造 / エピゲノム

Outline of Final Research Achievements

In this study, we develop statistical methods for predicting chromatin interaction regions from high-order epigenome information obtained from chromosome conformation capture techniques such as ChIA-PET and hi-C.
The outline of research results is described below. 1) probabilistic alignment for ChIA-PET sequencing tags to reference genome; 2) bias correction of ChIA-PET count data with Poisson regression model; 3) detection of chromatin interaction regions with Bayesian mixture model of negative binomial distributions; 4) detection of cell-type specific or signal dependent transcription factories; 5) development of pipelines for analyzing ChIA-PET sequencing data.

Research Products

• [Journal Article] NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells (2016)
  • Author(s): 1.Nakaoka HJ, Hara T, Yoshino S, Kanamori A, Matsui Y, Shimamura T, Sato H, Murakami Y, Seiki M, Sakamoto T
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 22784-22784
  • DOI: 10.1038/srep22784
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. (2016)
  • Author(s): R. Uchi (他40名, 山本36番目)
  • Journal Title: PLoS Genetics Volume: 12 Issue: 2 Pages: 1-24
  • DOI: 10.1371/journal.pgen.1005778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. (2016)
  • Author(s): G. Sawada (他43名, 山本21番目)
  • Journal Title: Gastroenterology Volume: 150 Issue: 5 Pages: 1171-1182
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma (2015)
  • Author(s): Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T, Takahashi Y, Kurashige J, Matsumura T, Ueo H, Takano Y, Ueda M, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Yamasaki M, Tanaka F, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Tanaka Y, Calin G, Miyano S, Doki Y, Mori M, Mimori K
  • Journal Title: PLoS One Volume: 10(10) Issue: 10 Pages: e0139808-e0139808
  • DOI: 10.1371/journal.pone.0139808
  • Peer Reviewed / Open Access
• [Journal Article] Integrated molecular analysis of adult T cell leukemia/lymphoma. (2015)
  • Author(s): Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, et al.
  • Journal Title: Nat Genet. Volume: 47(11) Issue: 11 Pages: 1304-15
  • DOI: 10.1038/ng.3415
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A likelihood-free filtering method via approximate Bayesian computation in evaluating biological simulation models (2015)
  • Author(s): Hasegawa T, Niida A, Mori T, Shimamura T, Yamaguchi R, Miyano S, Akutsu T, Imoto S
  • Journal Title: Computational Statistics & Data Analysis Volume: 94 Pages: 63-74
  • DOI: 10.1016/j.csda.2015.08.003
  • Peer Reviewed
• [Journal Article] Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs (2015)
  • Author(s): Nakata A, Yoshida R, Yamaguchi R, Yamauchi M, Tamada Y, Fujita A, Shimamura T, Imoto S, Higuchi T, Nomura M, Kimura T, Nokihara H, Higashiyama M, Kondoh K, Nishihara H, Tojo A, Yano S, Miyano S, Gotoh N
  • Journal Title: Scientific Report Volume: 5 Issue: 1 Pages: 13076-13076
  • DOI: 10.1038/srep13076
  • NAID: 120005764206
  • Peer Reviewed / Open Access
• [Journal Article] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. (2015)
  • Author(s): Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Hoshino N, Nagae G, Shiozawa Y, Okuno Y, Hosoi H, Tanaka Y, Okita H, Miyachi M, Souzaki R, Taguchi T, Koh K, Hanada R, Kato K, Nomura Y, Akiyama M, Oka A, Igarashi T, Miyano S, Aburatani H, Hayashi Y, Ogawa S, Takita J.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 7557-7557
  • DOI: 10.1038/ncomms8557
  • NAID: 120005623266
  • Peer Reviewed / Open Access
• [Journal Article] Genomic data assimilation using a higher moment filtering technique for restoration of gene regulatory networks (2015)
  • Author(s): Hasegawa T, Mori T, Yamaguchi R, Shimamura T, Miyano S, Imoto S, Akutsu T.
  • Journal Title: BMC Systems Biology Volume: 9 Issue: 1 Pages: 14-14
  • DOI: 10.1186/s12918-015-0154-2
  • NAID: 120005749949
  • Peer Reviewed / Open Access
• [Journal Article] Mutational landscape and clonal architecture in grade II and III gliomas (2015)
  • Author(s): Suzuki H, Aoki K, Natsume A, Ogawa S. et al.
  • Journal Title: Nat Genet. Volume: 47 Issue: 5 Pages: 458-468
  • DOI: 10.1038/ng.3273
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker (2014)
  • Author(s): Park H, Shimamura T, Miyano S, Imoto S
  • Journal Title: PLoS One Volume: 9(10) Issue: 10 Pages: e108990-e108990
  • DOI: 10.1371/journal.pone.0108990
  • Peer Reviewed / Open Access
• [Journal Article] Loss of CDCP1 expression promotes invasiveness and poor prognosis in esophageal squamous cell carcinoma. (2014)
  • Author(s): Sawada G, Takahashi Y, Niida A, Shimamura T, Kurashige J, Matsumura T, Ueo H, Uchi R, Takano Y, Ueda M, Hirata H, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Miyano S, Doki Y, Mori M, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: 4 Issue: S4 Pages: 640-647
  • DOI: 10.1245/s10434-014-3740-4
  • Peer Reviewed / Open Access
• [Journal Article] Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma (2014)
  • Author(s): Seki M, Yoshida K, Shiraishi Y, Shimamura T, Sato Y, Nishimura R, Okuno Y, Chiba K, Tanaka H, Kato K, Kato M, Hanada R, Nomura Y, Park MJ, Ishida T, Oka A, Igarashi T, Miyano S, Hayashi Y, Ogawa S, Takita J
  • Journal Title: Cancer Res Volume: 74 Issue: 10 Pages: 2742-9
  • DOI: 10.1158/0008-5472.can-13-2470
  • Peer Reviewed / Open Access
• [Journal Article] Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer (2014)
  • Author(s): Sugimachi K, Niida A, Yamamoto K, Shimamura T, Imoto S, Iinuma H, Shinden Y, Eguchi H, Sudo T, Watanabe M, Tanaka J, Kudo S, Hase K, Kusunoki M, Yamada K, Shimada Y, Sugihara K, Maehara Y, Miyano S, Mori M, Mimori K
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: S4 Pages: 3468-3476
  • DOI: 10.1245/s10434-013-3468-6
  • Peer Reviewed / Open Access
• [Journal Article] Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1. (2014)
  • Author(s): Barclay, S.S., Tamura, T., Ito H., Fujita, K., Tagawa, K., Shimamura, T., Katsuta, A., Shiwaku, H., Sone, M., Imoto, S., Miyano, S. and Okazawa, H.
  • Journal Title: Hum Mol Genet Volume: 23 Issue: 5 Pages: 1345-1364
  • DOI: 10.1093/hmg/ddt524
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. (2013)
  • Author(s): Kon A, Yoshida K
  • Journal Title: Nature Genet. Volume: 45 Issue: 10 Pages: 1232-1237
  • DOI: 10.1038/ng.2731
  • 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 Tumor-suppressive mir-497-195 cluster targets multiple cell-cycle regulators in hepatocellular carcinoma. (2013)
  • Author(s): Furuta M
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: e60155-e60155
  • DOI: 10.1371/journal.pone.0060155
  • Peer Reviewed
• [Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages (2013)
  • Author(s): Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M
  • Journal Title: Cancer Res Volume: 73 Issue: 10 Pages: 3019-3028
  • DOI: 10.1158/0008-5472.can-12-3231
  • Peer Reviewed
• [Journal Article] Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. (2013)
  • Author(s): Yokobori T, Iinuma H, Shimamura T, Imoto S, Sugimachi K, Ishii H, Iwatsuki M, Ota D, Ohkuma M, Iwaya T, Nishida N, Kogo R, Sudo T, Tanaka F, Shibata K, Toh H, Sato T, Barnard GF, Fukagawa T, Yamamoto S, Nakanishi H, Sasaki S, Miyano S, Watanabe T, Kuwano H, Mimori K, Pantel K, Mori M.
  • Journal Title: Cancer Res Volume: 1; 73(7) Issue: 7 Pages: 2059-69
  • DOI: 10.1158/0008-5472.can-12-0326
  • Peer Reviewed
• [Presentation] がんの俯瞰的理解のための統合的統計モデリング (2015)
  • Author(s): 島村徹平
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-02
  • Invited
• [Presentation] がん悪性化に寄与する発現制御調整因子のイン・シリコ探索 (2015)
  • Author(s): 島村徹平
  • Organizer: がんゲノムの情報と数理
  • Place of Presentation: 東京大学医科学研究所（東京都港区）
  • Year and Date: 2015-09-30
  • Invited
• [Presentation] Discovering modulators of gene regulation by local energy statistics (2015)
  • Author(s): Teppei Shimamura
  • Organizer: IFCS2015
  • Place of Presentation: ボローニャ大学（イタリア、ボローニャ）
  • Year and Date: 2015-07-07
  • Int'l Joint Research
• [Presentation] オミックスビッグデータ解析の現状と課題 (2015)
  • Author(s): 島村徹平
  • Organizer: 平成２６年度「複雑データの解析法に関する研究会」
  • Place of Presentation: 統計数理研究所（東京都立川市）
  • Year and Date: 2015-02-19
  • Invited
• [Presentation] Bayesian integrated analysis of chromatin interaction maps (2015)
  • Author(s): Shimamura T
  • Organizer: Pacific Symposium on Biocomputing 2015
  • Place of Presentation: The Fairmont Orchid, Hawaii （アメリカ、ハワイ州）
  • Year and Date: 2015-01-06
• [Presentation] オミクス解析におけるグラフィックス (2014)
  • Author(s): 島村徹平
  • Organizer: 日本計算機統計学会第２８回シンポジウム
  • Place of Presentation: 沖縄科学技術大学院大学（沖縄県恩納村）
  • Year and Date: 2014-11-15
  • Invited
• [Presentation] Systems analysis of cancer metabolism with constraint-based model of metabolic flux (2014)
  • Author(s): 島村徹平
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-10-17
  • Invited
• [Presentation] Integrative systems understanding of cancer metabolism with constraint-based modeling of metabolic flux (2014)
  • Author(s): 島村徹平
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] Hierarchical Bayes model-based analysis of chromatin interaction maps (2013)
  • Author(s): Shimamura T
  • Organizer: Genome Informatics
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
• [Presentation] Accurate detection of chromatin interactions from ChIA-PET sequencing data with a hierarchical Bayes model (2013)
  • Author(s): Shimamura T
  • Organizer: Clinical Genomics and Informatics Europe
  • Place of Presentation: Sheraton Hotel and Spa, Lisbon, Portugal
• [Presentation] 抗がん剤感受性予測に向けてのバイオインフォマティクスの現状と課題
  • Author(s): 島村徹平
  • Organizer: 日本計算機統計学会第27回大会
  • Place of Presentation: 青森県弘前大学
  • Invited