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Bioinformatics Core for Genomic Medicine and Biotechnology Development

Bioinformatics Core for Genomic Medicine and Biotechnology Development. I-Shou Chang, Ping-Chiang Lyu , Chao A. Hsiung, Jenn-Kang Hwang, H. Sunny Sun. National Health Research Institutes, National Tsing Hua University, National Chiao Tung University, and National Cheng Kung University.

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Bioinformatics Core for Genomic Medicine and Biotechnology Development

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  1. Bioinformatics Core for Genomic Medicine and Biotechnology Development I-Shou Chang, Ping-Chiang Lyu, Chao A. Hsiung, Jenn-Kang Hwang, H. Sunny Sun National Health Research Institutes, National Tsing Hua University, National Chiao Tung University, and National Cheng Kung University

  2. Infectious diseases Services Collaborative Research Education and Training Dissemination R & D Cancer research Highly heritable diseases Innovative research NRPGM Core Facilities TBI Supporting NRPGM GMBD Core GMBD Statistical Genetics Computational proteomics Comparative Genomics and Interactomes Structural Bioinformatics Applied Medical Genomics

  3. Web portal http://www.tbi.org.tw

  4. Online Services

  5. Mirror sites and Databases • Mirror sites PDB -Protein Data Bank SCOP -Structural Classification of Proteins PredictProtein server –Secondary structure, solvent accessible area prediction • In-house Databases SNP -SNP value-added database RegRNA -Regulatory RNA Motifs and Elements Database miRNAMap - Genomic Maps for microRNA CDSPD-CoDing region Sequence and Proteomic Database TAG-Tumor Associated Gene FlyDPI -Drosophila Database of Protein Interactomes hp-DPI -H. pylori Database of protein interactomes GPDB -Genome Profile Database dbPTM - Protein Post-Translational Modification Database Virtual 2D gel -Simulated 2D Gel for complete sequenced microbial genomes IM2PD -Integrated Microbial Metabolic Pathway Database SSDB -Disulfide Proteins Database pKnot –Protein knot structure database

  6. Analysis Tools • Homology & Similarity BLAST -Basic Local Alignment Search Tool         BLAST servers      PDB-BLAST -BLAST against PDB protein databank         RPS-BLAST -BLAST against Motif/Domain database      FASTA -Pair-wise Sequences Alignment • Sequence Analysis ClustalW -Web-based Multiple Sequence Alignment     PDA -Primer Design Assistant    RepeatMasker -Screening for low complexity DNA sequences [mirror ]    GPRM - Genetic Programming for RNA Motifs GenePredict -Web-based gene prediction service KinasePhos -Predict phosphorylation sites within given protein sequences      SpliceInfo -An information repository for mRNA alternative splicing ProSplicer -An Alternative Splicing Database based on Protein, mRNA, and EST Sequences      MuSiC -Multiple Sequence Alignment with Constraints GPRM Genetic Programming for RNA Motifs RNAMST -An efficient and flexible search tool for RNA structural homologs CELLO -Prediction of protein subcellular localization

  7. Analysis Tools GMBD RegRNA A Regulatory RNA Motifs and Elements Finder ESTviewer A Web interface for visualizing ESTs PSEP System A Comparative Method for Identification of Gene Structures and Alternatively Spliced Variants ENACE System Identification and evolutionary analysis of novel exons and alternative splicing events • Phylogenetic Analysis POWER -Phylogenetic Web Repeater • Proteomics KPST -Pathway search tool for KEGG RMA - A Reinforced Merging methodology for mapping unique peptide Tm Predictor - Melting Temperature Prediction : Predict thermal stability of proteins • Structural Analysis SARST -Structure Alignment by Ramachandran Search Tool StEQ - Structural Entropy Query SDSE - Sequence Derived Structure Entropy (PS)2 -Protein Structure Prediction Server GEMDOCK -Generic Evolutionary Method for molecular DOCKing ProKware -A graphic web server for presenting protein structural properties

  8. Analysis Tools • Miscellaneous Tools － GCG -Wisconsin Sequence Analysis Package     － SeqWeb -Web-based GCG － EMBOSS -European Molecular Biology Open Software Suite     － JEMBOSS -Java user interface of EMBOSS － EMBOSS GUI -Web-based service of EMBOSS

  9. Software • Incorporating endophenotypes in linkage analysis • Break point search based on array-CGH data • Segregation analysis based on onset time • Time course transcription profile of virus genome

  10. Usage of hp-DPI : H. pylori Database of protein interactomes Accumulative visits of hp-DPI, Nov. 2004 to Nov. 2007

  11. Usage of PDA-Primer Design Assistant Accumulative sequences submitted to/visits of PDA, Jul. 2003 to Nov. 2007

  12. Training and Education

  13. International symposium: 1255 people attended • Bioinformatics workshops: 3,037 participants Activities 2003-2007 Mini symposia Microarray analysis workshop, held in Academia Sinica, 2004 (122) Bioinformatics and applied medical genomics, held in NCKU, 2004 Workshop on Virus Evolution and Molecular Epidemiology, NHRI, Zhunan, 2005 (157) Workshop on Statistical Genomics, held in NHRI Zhunan Campus, 2006 (119) Structural Bioinformatics Workshop, held in NCKU, 2006 From Sequences, Structure to Systems Courses and Hands-on Workshop held island-wide GMBD Core Services Workshop(471) Workshop on sequence analysis tools: The Wisconsin Package and EMNOSS suite(1,281) Workshop on Genetics, Evolution and Bioinformatics Structural bioinformatics and drug design workshop Workshop on Analysis Methods of Genomic Research (65) Bioinformatics in medical application Phylogenetic Analysis Workshop(319) Workshop in systems biology and in genetic regulatory networks (in BIT2005)

  14. Course News • 結構生物資訊學研習會 (2008.09) 課程時間：九月四日(星期四)至九月五日(星期五) 上課地點：中國醫藥大學互助大樓7F電腦教室 課程大綱：由蛋白質基本概念、功能以及結構介紹起，接著介紹世界上與蛋白質研究相關的資料庫及各式工具，同時搭配GMBD Core Service Website中的工具，輔助介紹蛋白質功能與結構分析上的各項研究。 • 親緣演化分析研習會 (2008.10) 介紹親緣演化分析基本理論、建構演化樹之方法，以及不同演化樹所代表的意義，並配合常用之親緣演化分析軟體的實際操作

  15. Systems Biology Package Workshop(NCKU) Course News

  16. Research and Development

  17. Translate developments into web services: • Provide 14 in-house databases and 26 in-house tools • Published 102 papers in years 2003-2007 • There are 28 tools/databases under development

  18. Web services under development • Statistical Genetics, Comparative Genomics and Interactomes CDSPD－CoDing Sequence and Proteomics Database studies. EFG－ Extractor of Feature sequence from GenBank MOLAS-Lite－ Microarray OnLine Analysis System UPS－ Unique Probe Selector My BLAST－ Customized BLAST server Hubba-Hubba－ Hub Object Analyzer AMP－Automatic Model Selector for Phylogenetic Analysis Hum-DPI－ Interactome of Human Yeast-DPI－ Interactome of yeast Caption－Interactome of C. ablicans

  19. Web services under development • Computational Proteomics GPTB－ Genome/Proteom Tree Builder IP-SARST－ Integrated Protein Search Aided by Ramachandran Sequential Transformation CELLO II－ An integrated method to predict protein subcellular localization using SVM and sequence alignment Re-MUSIC－ The web tool for multiple sequence alignment with regular expression constraints KinasePhos 2.0－ A web server for identifying protein kinase-specific phosphorylation sites

  20. Web services under development • Structural Bioinformatics 3D partner－A web server to predict interacting partners and binding models Sspred－Disulfide connectivity predictor Fast structure alignment server－ A web server to provide fast protein structure alignment The Protein Knot Server－ A web server for detecting protein knots as well as the database of all knotted proteins Automatic structure recognition server－A web server to automatically recognize protein structure domains Database of protein fluctuations－Computation of protein dynamics and correlated motions using weighted protein contact model

  21. Web services under development • Applied Medical Genomics SNP-VAD－ SNP value-added database LCR database－ Low-copy-repeat (LCR) database BEST－ The binding element searching tools Methylome－ Genome-wide methylation tagging map Repetitome－ Whole genome repetitive elements map ViTa－ A database of host microRNA targets on viruses

  22. Research Highlights

  23. General bioinformatics tools to facilitate GM research • Sequence analysis and value-added databases • PDA（Primer Design Assistant） • POWER（Phylogenetic Web Repeater） • Molecular typing of enterovirus • Human-specific indels : Comparative genomics approach • Predicting antigenic variants of Influenza A virus • CDSPD（CoDing region Sequence and Proteomic Database） • TAG (Tumor Associated Genes) • LCR (Low-copy Repeats Database) • The BEST (Binding Element Searching Tool) • Value-added SNP (single nucleotide polymorphism) database Nucleic Acids Res. 2003, 31: 3751-3754 Nucleic Acids Res. 2005, 33: 553-556 Virus Genet. 2005, 21(3)337-347 Genome Res. 2007, 17:16-22 Bioinformatics, under revision NAR Molecular Database Online #922, 2007 Gemomics 2006, 87:290-297 Nucleic Acids Res. 2005, 33: 5190-5198

  24. General bioinformatics tools to facilitate GM research • Transcriptome analysis-Microarray Studies • MOLAS（Microarray on-line Analysis System） • Array CGH analysis • Time course analysis for virus genes • Protein interactomes • Hp-DPI (H. pylori Database of protein interactomes) • Fly-DPI (Drosophila Database of Protein Interactomes) • C. albicans-DPI • EBV-DPI • Genetic analysis • Incorporating endophenotypes into allele-sharing based linkage tests • Genetic statistic server Stat. Appl. In Gen. & Mol. Biol. 2006 J. of Virol. 2006, 80(18):8989-99 Bioinformatics 2005, 21: 1288-1290 BMC Bioinformatics, 2006, 7: S18 Genet. Epid., 2006

  25. Yu et al. Protein Science (2004); Proteins (2006) NATURE REVIEWS Microbiology (2006) 4, 741-751 Methods for predicting bacterial protein subcellular localization • A review article in Nat Rev Microbiol introduced CELLO in 2006. • The world largest human vaccine company Sanofi Pasteur has requested a site licenses of CELLOfrom our core.

  26. NAR Molecular Database Online #922, 2007 Visitors around the world The TAG

  27. NRPGM Bioinformatics CoresImpact on Research

  28. Collaborative Research

  29. Collaborative Research Serves as partner in bioinformatics to the research community • Collaborated with 31 PIs in 21 institutions • Participated in NRPGM and many other research projects • Published 46 papers in years 2003-2007

  30. Collaborative Research Collaboration with NRPGM projects • NRPGM Research Projects Highly Heritable Diseases Infectious Diseases Liver Cancer Lung Cancer Innovative Researches • NRPGM Core Facilities Proteomics and Structural Biology Research Core High-field Macromolecular NMR Core Facility RNAi Core Tumor Tissue Bank Core

  31. Collaborative Research GMBD Collaboration with other National Research Projects • National Research Program for Nano sciences and technologies • National Research Program for Biotechnology and Drug Development • National Science and Technology Program for Agricultural Biotechnology

  32. Innovative research: structural genomics 2BO3 2GU9 2FUJ 1XS3 2CMG Collaboration in Stuctural Genomics projects have generated more than 30 protein structures and 20 papers. 2GSC 1ZUH 2DYU 2BQX 2FA5 2E11 2E12 2GBZ 2CMH 2FUK

  33. Collaborative Research with other National Research Program projects PNAS (2006) 103, 14412

  34. GemDOCK has been cited more than 50 times since published Collaborative research

  35. Structural Genomics Projects Collaborative research Klebsiella pneumoniae http://kp.life.nthu.edu.tw/ Xanthomonas campestris http://xcc.life.nthu.edu.tw/ Helicobacter pylori http://hp.life.nthu.edu.tw/ Stenotrophomonas maltophilia http://sm.life.nthu.edu.tw/

  36. Contact • For Collaboration National Health Research Institutes Dr. I-Shou Chang (張憶壽教授), Dr. Chao Agnes Hsiung (熊昭教授) National Tsing-Hua University Dr. Ping-Chiang Lyu (呂平江教授) National Chiao-Tung University Dr. Jenn-Kang Hwang (黃鎮剛教授) National Cheng Kung University Dr. H. Sunny Sun (孫孝芳教授) • Help Desk: Phone: 037-246166 ext 33621 Fax: 037-586410 email : service@tbi.org.tw

  37. Thank you!

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