計算アプローチによる肝炎の病態・治療に関する分子機構の解明

• 研究課題/領域番号: 23300105
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 統計科学
• 研究機関: 北陸先端科学技術大学院大学
• 研究代表者: TUBAO Ho (TU・BAO Ho) 北陸先端科学技術大学院大学, 知識科学研究科, 教授 (60301199)
• 研究分担者: 高林 克日己 千葉大学, 医学部付属病院, 教授 (90188079) ; 横須賀 収 (横須賀 收) 千葉大学, 医学部, 教授 (90182691) ; 神田 達郎 千葉大学, 医学(系)研究科(研究院), 講師 (20345002) ; DAH Hieuchi (DAM HieuChi) 北陸先端科学技術大学院大学, 知識研科, 准教授 (70397230) ; 河崎 さおり 北陸先端科学技術大学院大学, 先端領域社会人教育院, 先端領域社会人教育院 (40377437)
• 研究期間 (年度): 2011-04-01 – 2014-03-31
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 20,280千円 (直接経費: 15,600千円、間接経費: 4,680千円); 2013年度: 5,460千円 (直接経費: 4,200千円、間接経費: 1,260千円); 2012年度: 5,850千円 (直接経費: 4,500千円、間接経費: 1,350千円); 2011年度: 8,970千円 (直接経費: 6,900千円、間接経費: 2,070千円)
• キーワード: 医薬生物 / 統計解析 / データマイニング / data mining / machine learning / interferon/vibavirin / hepatitis pathogenesis / HCV / siRNA / epigenetics / hepatitis C virus / 知識発見 / 科学データ / 構造化データ

研究概要

第1課題のHCV NS5AのIFN-RBV治療への耐性機序について、多数のNS5Aデータにおいて著効データが少数である場合に有効な準教師付アンサンブル学習手法を開発し、SVRと非SVRの2種の患者群を特徴づけるモチーフを発見した。第2課題のsiRNA抑制効果用に開発した手法では、既知の設計規則に加え2種の新siRNA設計規則を発見し、また他手法では所与のsiRNA配列についてスコアと著効情報をもつ配列と既知の規則で配列の表現力を補強し、新規のテンソル回帰手法にて予測精度を大幅に改善した。第3課題ではエピジェネティク因子と肝炎進行の相互作用に関するヒストン修飾の因果関係網等の中間結果を得た。

研究成果

• [雑誌論文] Hepatitis C virus NS5A inhibitors and drug resistance mutations (2014)
  • 著者名/発表者名: Nakamoto, S., Kanda, T., Wu, S., Shirawasa, H., Yokosuka, O
  • 雑誌名: World Journal of Gastroenterol 巻: 20(11) ページ: 2902-12
  • 査読あり
• [雑誌論文] Modeling the diversity and log-normal of data (2014)
  • 著者名/発表者名: Than, K., Ho, T.B
  • 雑誌名: Intelligent Data Analysis 巻: (in press)
  • NAID: 120005528191
  • 査読あり
• [雑誌論文] Treatment of hepatitis C virus infection in the future (2014)
  • 著者名/発表者名: Kanda T, Yokosuka O, Omata M
  • 雑誌名: Clinical Translation Medicine 巻: 11, 2(1):9
  • 査読あり
• [雑誌論文] An effective framework for supervised dimension reduction the diversity and log-normal of data (2014)
  • 著者名/発表者名: Than K., Ho T.B, Nguyen, D.K.
  • 雑誌名: Neurocomputing, ELsevier 巻: accepted
• [雑誌論文] Data mining for materials design: A computational study of suingle molecule magnet (2014)
  • 著者名/発表者名: Dam, H.C., Pham, T.L., Ho, T.B., Nguyen, T.A., Nguyen, V.C.
  • 雑誌名: The journal of Chemical Physics 巻: Vol. 40, Issue 4 ページ: 400101-1
• [雑誌論文] Hepatitis C virus NS5A inhibitors and drug resistance mutations (2014)
  • 著者名/発表者名: Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Hiroshi Shirasawa, Osamu Yokosuka
  • 雑誌名: World Journal of Gastroenterology 巻: 20(11) ページ: 2902-2912
• [雑誌論文] A Semi-Supervised Learning Method for Discriminative Motif Finding and Its Application (2013)
  • 著者名/発表者名: Le, N., Ho, T.B., Kanda, T., Kawasaki, S., Takabayashi, K., Wu, S., Yokosaka, O
  • 雑誌名: Journal of Universal Computer Scienc 巻: Vol.19.No.4 ページ: 563-580
  • 査読あり
• [雑誌論文] Antiviral therapy for " difficult -to-treat" hepatitis C virus-infected patients (2013)
  • 著者名/発表者名: Kanda T, Yokosuka O, Omata M
  • 雑誌名: Chin Med J (Engl) 巻: 126(23) ページ: 4568-74
  • 査読あり
• [雑誌論文] Natural interferon-beta plus ribavirin therapy led to sustained virological response after seven unsuccessful courses of anti-viral treatment in a chronic hepatitis C patient (2013)
  • 著者名/発表者名: Kandat T., Nakamoto S., Arai, M., Miyamura, T., Wu, S., Fujiwara, K., Yokosuka O
  • 雑誌名: Clinical Journal Gastroentorology 巻: 6(2) 号: 2 ページ: 160-163
  • DOI: 10.1007/s12328-013-0366-1
  • 査読あり
• [雑誌論文] Platelet count and sustained virological response in hepatitis C treatment (2013)
  • 著者名/発表者名: Kandat T., Kato K., Tsubota, A., Takada, N., Nishino, T., Mikami, S., Miyamura, T., Maruoka D., We, S., Nakamoto, S., Arai, M., Fujiwara, K., Imazeki, F., Yokosuka O
  • 雑誌名: World Journal of Hepatology 巻: 5(4) ページ: 182-188
  • 査読あり
• [雑誌論文] A Semi- Supervised Learning Method for Discriminative Motif Finding and Its Application (2013)
  • 著者名/発表者名: Le N., Ho T.B., Kanda T., Kawasaki S., Takabayashi K., Wu S., Yokosuka O.
  • 雑誌名: Universal Computer Science 巻: 19(4) ページ: 563-580
• [雑誌論文] Hepatitis C virus protease inhibitor-resistance mutations: Our experience and review (2013)
  • 著者名/発表者名: Shuang Wu, Tatsuo Kanda, Shingo Nakamoto, Fumio Imazeki, Osamu Yokosuka
  • 雑誌名: World Journal of Gastroenterology 巻: 19(47) ページ: 8940-8948
• [雑誌論文] Platelet count and sustained virological response in hepatitis C treatment (2013)
  • 著者名/発表者名: Tatsuo Kanda, Keizo Kato, Akihito Tsubota, Nobuo Takada, Takayoshi Nishino, Shigeru Mikami, Tatsuo Miyamura, Daisuke Maruoka, Shuang Wu, Shingo Nakamoto, Makoto Arai, Keiichi Fujiwara, Fumio Imazeki, Osamu Yokosuka
  • 雑誌名: World journal of hepatology 巻: 5(4) ページ: 182-188
  • 査読あり
• [雑誌論文] Computational reconstruction of transcriptional relationships from ChIP-Chip data, IEEE-ACM Trans (2012)
  • 著者名/発表者名: Le, N.T, Ho, T.B., Ho, B.H
  • 雑誌名: On Computational Biology and Bioinformatics 巻: Vol.10.No.2 ページ: 300-307
  • 査読あり
• [雑誌論文] Quantitatively assessing the effect of regulatory factors on nucleosome dynamics (2012)
  • 著者名/発表者名: Ho, B.H., Le, N.T., Ho, T.B
  • 雑誌名: Journal of Ambient Intelligence and Humanized Computing, Springer 巻: Vol.3,Issue4 ページ: 265-280
  • 査読あり
• [雑誌論文] The cutting-edge of medicine. Application of medical informatics in internal medicine (2012)
  • 著者名/発表者名: Takabayashi K.
  • 雑誌名: Nihon Naika Gakkai Zasshi 巻: 10;101(11) ページ: 3239-46
  • 査読あり
• [雑誌論文] Quantitatively assessing the effect of regulatory factors on nucleosome dynamics (2012)
  • 著者名/発表者名: Ho, B.H., Le, N.T., Ho, T.B.
  • 雑誌名: Journal of Ambient Intelligence and Humanized Computing, Springer 巻: 3(4) ページ: 265-280
  • 査読あり
• [雑誌論文] Enhancing privacy for frequent itemset mining in vertically distributed data (2012)
  • 著者名/発表者名: Luong, T.D., Ho, T.B., Tran, D.H.
  • 雑誌名: Journal of Information Technologies and Communications 巻: Vol. E-2, No.5(9) ページ: 25-39
  • 査読あり
• [雑誌論文] Computational reconstruction of transcriptional relationships from ChIP-Chip data (2012)
  • 著者名/発表者名: Le, N.T, Ho, T.B., Ho, B.H.
  • 雑誌名: IEEE-ACM Trans. on Computational Biology and Bioinformatics 巻: Vol. 10. No. 2 ページ: 300-307
  • NAID: 120004462282
  • 査読あり
• [雑誌論文] Auto-Selection of DPC Codes from Discharge Summaries by Text Mining in Several Hospitals and Analysis of Differences in Discharge Summaries (2012)
  • 著者名/発表者名: Doi S., Suzuki T., Takabayashi K. et al.
  • 雑誌名: J. Adv. Compt. Intel. and Intelligence Informatics 巻: 16(1) ページ: 48-54
• [雑誌論文] Detecting Disease Genes Based on Semi-Supervised Learning and Protein-Protein Interaction Networks (2011)
  • 著者名/発表者名: Nguyen, T.P., Ho, T.B
  • 雑誌名: Artificial Intelligence in Medicine 巻: Vol.54 ページ: 63-71
  • 査読あり
• [雑誌論文] microRNA expression profiles for classification and analysis of tumor samples (2011)
  • 著者名/発表者名: Tran, D.H., Ho, T.B., Pham, T.H., Satou, K
  • 雑誌名: IEICE Trans. Information Systems 巻: E94.D(3) ページ: 416-422
  • NAID: 10028232115
  • 査読あり
• [雑誌論文] Detecting Disease Genes Based on Semi-Supervised Learning and Protein-Protein Interaction Networks (2011)
  • 著者名/発表者名: Nguyen, T.P., Ho, T.B.
  • 雑誌名: Artificial Intelligence in Medicine 巻: 54 ページ: 63-71
  • 査読あり
• [雑誌論文] microRNA expression profiles for classification and analysis of tumor samples (2011)
  • 著者名/発表者名: Tran, D.H., Ho, T.B., Pham, T.H., Satou, K.
  • 雑誌名: IEICE Trans.Information Systems 巻: E94.D(3) ページ: 416-422
  • NAID: 10028232115
  • 査読あり
• [学会発表] A nucleosomal approach to inferring causal rela- tionships of histone modifications (2014)
  • 著者名/発表者名: Le, N.T, Ho, T.B., Ho, B.H., Tran, D.H
  • 学会等名: Asia-Pacific Bioinformatics Conference APBC 2014
  • 発表場所: Shanghai, China
• [学会発表] A novel framework to improve siRNA efficacy prediction (2014)
  • 著者名/発表者名: Bui N.T., Ho. T.B.
  • 学会等名: Pacific-Asia Conference on Knowledge Discovery and Data Mining PAKDD'04
  • 発表場所: Tainan, Taiwan
• [学会発表] A nucleosomal approach to inferring causal relationships of histone modifications (2014)
  • 著者名/発表者名: Le, N.T, Ho, T.B., Ho, B.H., Tran, D.H.
  • 学会等名: Asia-Pacific Bioinformatics Conference APBC 2014
  • 発表場所: Shanghai, China
• [学会発表] A novel framework to improve siRNA efficacy prediction (2014)
  • 著者名/発表者名: Bui N.T., Ho, T.B.
  • 学会等名: Pacific-Asia Conference on Knowledge Discovery and Data Mining PAKDD'04
  • 発表場所: Tainan, Taipei
• [学会発表] Simplicial Nonnegative Matrix Factorization (2013)
  • 著者名/発表者名: Nguyen, D.K., Than, K., Ho, T.B
  • 学会等名: IEEE International Conference on Research, Innovation and Vision for Future, RIVF 2013
  • 発表場所: Hanoi, Vietnam
• [学会発表] Reconstruction of Triple-wise Relationships in Biological Networks from Profiling Data (2013)
  • 著者名/発表者名: Nguyen, Q.D., Pham, T.H., Ho, T.B., Nguyen, V.H., Tran, D.H
  • 学会等名: The 9th International Conference on Computing and Information Technology (IC2IT2013)
  • 発表場所: Thailand
• [学会発表] An Effective Method for Generating siRNA Design Rules (2013)
  • 著者名/発表者名: Bui, N.T., Ho, T.B., Kawasaki, S
  • 学会等名: The 5th Asian Conference On Intelligent Information and Database Systems, ACIID 2013, Kuala Lumpur
  • 発表場所: Malaysia
• [学会発表] A Review on Data Mining Approach for Adverse Drug Reaction Research (2013)
  • 著者名/発表者名: Taewijit, S., Ho, T.B., Theeramunkong, T.
  • 学会等名: Second Asian Conference on Information System, ACIS 2013
  • 発表場所: Phukhet, Thailand
• [学会発表] An Effective Method for Generating siRNA Design Rules (2013)
  • 著者名/発表者名: Bui, N.T., Ho, T.B., Kawasaki, S.
  • 学会等名: 5th Asian Conference On Intelligent Information and Database Systems, ACIID 2013
  • 発表場所: Kuala Lumpur, Malaysia
• [学会発表] Le, T.N., Bui, N.T., Than, Q.K., From Clinical to Genomics Data in Hepatitis Study (2012)
  • 著者名/発表者名: Ho, T.B., Takabayashi, T., Kanda, T., Kawasaki, S.
  • 学会等名: The First Asian Conference on Information Systems
  • 発表場所: Cambodia
• [学会発表] A Sequential Apriori Algorithm for Discriminative Design Rules of Effectiv siRNA Sequences (2012)
  • 著者名/発表者名: Bui, N.T., Ho, T.B., Kawasaki, S
  • 学会等名: 13th International Symposium on Knowledge and Systems Science
  • 発表場所: Kanazawa
• [学会発表] Analysis of gene expression behaviour by nucleosome and protein binding profiles (2012)
  • 著者名/発表者名: Ho, B.H., Ho, T.B
  • 学会等名: The 10th Asia Pacific International Conference on Bioinformatics and Biomedical Technology, ICBBT 2012
  • 発表場所: Singapore.
• [学会発表] Analysis of functional linkages between nucleosome dynamics and transregulatory factors (2012)
  • 著者名/発表者名: Ho, B.H., Le, N.T., Ho, T.B
  • 学会等名: 4th International Conference on Bioinformatics and Biomedical Technology 2012, BICoB -2012
  • 発表場所: Las Vegas, USA.
• [学会発表] Computational reconstruction of transcriptional relationships from ChIPChip data (2012)
  • 著者名/発表者名: Le, N.T., Ho, T.B., Ho, B.H
  • 学会等名: The 10th Asia Pacific Bioinformatics Conference
  • 発表場所: Melbourne, Australia
• [学会発表] Multivariate Mutual Information Measures for Discovering Biological Networks (2012)
  • 著者名/発表者名: Pham, T.H., Ho, T.B., Nguyen, Q.D., Nguyen, V.H., Tran, D.H
  • 学会等名: IEEE RIVF International Conference on Information and Communication Technologies, Ho Chi Minh City
  • 発表場所: Vietnam
• [学会発表] A Semi-Supervised Method for Discriminative Motif Finding and Its Application to Hepatitis C Virus Study (2012)
  • 著者名/発表者名: Le, N., Ho, T.B
  • 学会等名: 4th Asian Conference on Intelligent Information and Database Systems ACIIDS 2012
  • 発表場所: Kaohsiung, Taiwan
• [学会発表] From Clinical to Genomics Data in Hepatitis Study (2012)
  • 著者名/発表者名: Ho, T.B., Takabayashi, T., Kanda, T., Kawasaki, S., Le, T.N., Bui, N.T., Than, Q.K.
  • 学会等名: The First Asian Conference on Information Systems
  • 発表場所: SiemRiep, Cambodia
• [学会発表] A Sequential Apriori Algorithm for Discriminative Design Rules of Effective siRNA Sequences (2012)
  • 著者名/発表者名: Bui, N.T., Ho, T.B., Kawasaki, S.
  • 学会等名: 13th International Symposium on Knowledge and Systems Science
  • 発表場所: Kanazawa, Japan
• [学会発表] Analysis of gene expression behaviour by nucleosome and protein binding profiles (2012)
  • 著者名/発表者名: Than, K., Ho, T.B., Pham, N.K., Nguyen, D.K.
  • 学会等名: Supervised dimension reduction with topic model
  • 発表場所: Singapore
• [学会発表] Reconstruction of Triple-wise Relationships in Biological Networks from Profiling Data (2012)
  • 著者名/発表者名: Nguyen, Q.D., Pham, T.H., Ho, T.B., Nguyen, V.H., Tran, D.H.
  • 学会等名: The 9th International Conference on Computing and Information Technology (IC2IT2013)
  • 発表場所: Singapore
• [学会発表] Computational reconstruction of transcriptional relationships from ChIP-Chip data (2012)
  • 著者名/発表者名: Le, N.T, Ho, T.B., Ho, B.H.
  • 学会等名: The 10th Asia Pacific Bioinformatics Conferenee
  • 発表場所: Melbourne, Australia
• [学会発表] Analysis of gene expression behaviour by nucleosome and protein binding profiles (2012)
  • 著者名/発表者名: Ho, B.H., Ho, T.B.
  • 学会等名: The 10th Asia Pacific International Conference on Bioinformatics and Biomedical Technoloey, ICBBT 2012
  • 発表場所: Singapore
• [学会発表] Multivariate Mutual Information Measures for Discovering Biological Networks (2012)
  • 著者名/発表者名: Pham,T.H., Ho, T.B., Nguyen, Q.D., Nguyen, V.H., Tran, D.H.
  • 学会等名: IEEE RIVF International Conference on Information and Communication Technologies
  • 発表場所: Ho Chi Minh City, Vietnam
• [学会発表] Analysis of functional linkages between nucleosome dynamics and trans-regulatory factors (2012)
  • 著者名/発表者名: Ho, B.H., Le, N.T., Ho, T.B.
  • 学会等名: 4th International Conference on Bioinformatics and Biomedical Technology 2012, BICoB-2012
  • 発表場所: Las Vegas, USA
• [学会発表] Finding HCV NS5A Discriminative Motifs for Assessment of IFN/Ribavarin Therapy Effect (2011)
  • 著者名/発表者名: Ho, T.B., Kawasaki, S., Le, N.T., Kanda, T., Le, T.N., Takabayashi, K., Yokosuka, O
  • 学会等名: Workshop Data Mining in Genomics and Proteomics, International Conference ECML/PKDD
  • 発表場所: Athens, Greece
• [学会発表] Reconstruction of histone modification network from next-generation sequencing dat (2011)
  • 著者名/発表者名: Le, N.T., Ho, T.B
  • 学会等名: IEEE International Conference on Bioinformatics and Bioengineering BIBE 2011
  • 発表場所: Taichung, Taiwan
• [学会発表] Simulation-based Data Mining Solution to the Structure of Water Surrounding Proteins (2011)
  • 著者名/発表者名: Dam, H.C., Ho, T.B., Sugiyama, A.
  • 学会等名: The 10th Asia Pacific Bioinformatics Conferenee
  • 発表場所: Barcelona, Spain
• [学会発表] Reconstruction of histone modification network from next-generation sequencing data (2011)
  • 著者名/発表者名: Le, N.T., Ho, T.B
  • 学会等名: IEEE International Conference on Bioinformatics and Bioengineering BIBE 2011
  • 発表場所: Taichung, Taiwan
• [学会発表] A Distributed Solution for Privacy Preserving Outlier Detection (2011)
  • 著者名/発表者名: Luong, T.D., Ho, T.B.
  • 学会等名: The Third International Conference on Knowledge and Systems Engineering
  • 発表場所: Hanoi, Vietnam
• [図書] Lecture Notes in Artificial Intelligence LNAI 8443, Advances in Knowledge Discovery and Data Mining (Eds.) (2014)
  • 著者名/発表者名: Tseng, V.S., Ho, T.B., Zhou, Z.-H., Chen, A.L.P., Kao, H.-Y.
  • 総ページ数: 2500
  • 出版者: Springer
• [図書] Mining multiple biological data for reconstructing signal transduction networks (book chapter), Data Mining : Foundations and Intelligent Paradigms D.E. Holmes, L.C. Jain (Eds.) (2011)
  • 著者名/発表者名: Nguyen, T.P., Ho, T.B.
  • 出版者: Springer Verlag
• [図書] Knowledge Discovery (Chapter 4), Knowledge Technology and Science, Y.Nakamori (Ed.) (2011)
  • 著者名/発表者名: Ho, T.B.
  • 出版者: CRC Press and Taylor & Francis
• [図書] Mining multiple biological data for reconstructing signal transduction networks, Data Mining : Foundations and Intelligent Paradigms, D.E.Holmes, L.C.Jain (Eds.) (2011)
  • 著者名/発表者名: Nguyen, T.P., Ho, T.B.
  • 出版者: Springer-Verlag