Elucidation of the molecular mechanisms on the pathology and treatment of hepatitis by computational approach

• Project/Area Number: 23300105
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Statistical science
• Research Institution: Japan Advanced Institute of Science and Technology
• Principal Investigator: 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)
• Co-Investigator(Kenkyū-buntansha): TAKABAYASHI Katsuhiko 千葉大学, 医学部付属病院, 教授 (90188079) ; YOKOSUKA Osamu 千葉大学, 医学部, 教授 (90182691) ; KANDA Tatsuo 千葉大学, 医学(系)研究科(研究院), 講師 (20345002) ; DAM Hieu Chi 北陸先端科学技術大学院大学, 知識研科, 准教授 (70397230) ; KAWASAKI Saori 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)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 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

Research Abstract

For the first task on HCV NS5A resistance mechanisms to interferon/ribavirin therapy, our semi-supervised ensemble method discovered the motifs that well characterizing two class of patients with SVR and non-SVR, especially in case of only a small number labelled NS5A sequences but much unlabelled sequences are available. For the second task on the knockdown efficacy of siRNA, one of our method discovered two siRNA design rules in addition to known design rules, and the other significantly improve the predictive ability for given siRNA sequences. This method employs both scored and labelled sequences as well as known design rules to enrich the poor sequence representation of siRNA by transformed matrices. The prediction is done by a novel tensor regression method on those matrices. For the third task on the interplay between epigenetic factors and hepatitis progression, we reached some intermediate results such as inferring the causual relationship network of histone modifications.

Research Products

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