Bioinformatics Core for Genomic Medicine and Biotechnology Development

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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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TBI
Supporting NRPGM
GMBD Core
GMBD
Statistical Genetics
Computational proteomics
Comparative Genomics and Interactomes
Structural Bioinformatics
Applied Medical Genomics
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Web portal
http//www.tbi.org.tw
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Online Services
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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

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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

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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

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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

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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

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Usage of hp-DPI H. pylori Database of protein
interactomes
Accumulative visits of hp-DPI, Nov. 2004 to Nov.
2007
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Usage of PDA-Primer Design Assistant
Accumulative sequences submitted to/visits of
PDA, Jul. 2003 to Nov. 2007
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Training and Education
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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 Phyloge
netic Analysis Workshop(319) Workshop in systems
biology and in genetic regulatory networks (in
BIT2005)
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Course News

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Systems Biology Package Workshop (NCKU)
Course News
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Research and Development
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• 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

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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
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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
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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
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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
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Research Highlights
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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, 1716-22
Bioinformatics, under revision
NAR Molecular Database Online 922, 2007
Gemomics 2006, 87290-297
Nucleic Acids Res. 2005, 33 5190-5198
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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
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NATURE REVIEWS Microbiology (2006) 4,
741-751 Methods for predicting bacterial protein
subcellular localization

1. A review article in Nat Rev Microbiol introduced
   CELLO in 2006.
2. The world largest human vaccine company Sanofi
   Pasteur has requested a site licenses of CELLO
   from our core.

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The TAG
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NRPGM Bioinformatics Cores Impact on Research
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Collaborative Research
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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

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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

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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

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Innovative research structural genomics
1XS3
2CMG
2GU9
2FUJ
2BO3
Collaboration in Stuctural Genomics projects have
generated more than 30 protein structures and 20
papers.
2GSC
1ZUH
2FA5
2DYU
2BQX
2E12
2E11
2GBZ
2CMH
2FUK
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Collaborative Research with other National
Research Program projects
PNAS (2006) 103, 14412
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• Collaborative research

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• Collaborative research

Structural Genomics Projects
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/
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Contact

• For Collaboration
• National Health Research Institutes
• Dr. I-Shou Chang (?????), Dr. Chao
  Agnes Hsiung (????)
• National Tsing-Hua University
• Dr. Ping-Chiang Lyu (?????)
• National Chiao-Tung University
• Dr. Jenn-Kang Hwang (?????)
• National Cheng Kung University
• Dr. H. Sunny Sun (?????)
• Help Desk
• Phone [phone] ext 33621
• Fax [phone]
• email service_at_tbi.org.tw

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Thank you!