Transcript Various Career Options Available

Introduction and Importance of
Bioinformatics: Application in
Drug/Vaccine Design
G. P. S. Raghava
Email: [email protected]
Web: http://www.imtech.res.in/raghava/
What is Bioinformatics (BI) ?
Historical Background
Why Bioinformatics is Required
Core of Bioinformatics
Important Applications of BI
Future Prospectus of Bioinformatics
Bioinformatics mines data
Db
What is Bioinformatics
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Biocomputing: Application of Computer in
Biosciences
Biocomputing started in 1960’s
Explosion of Genomic Data
Access and Management of Data
Biocomputing+Information Science
Role of Internet in BI
Brief History
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1953: DNA structure discovered
1960 Assembly of protein sequence database - PIR
1977: Sanger sequencing technique developed
1979 GenBank prototype was conceived
1980 EMBL database was founded
1988: Human Genome project initiated
1993 The first genome database ACEDB (C.
elegans)
1995: Influenza genome sequenced (5Mb)
1998: High throughput sequencing machine
developed by PE Biosystems
2000: Drosophila genome sequenced (180Mb)
2001: Human genome rough draft (2.91Bb)
Why Bioinformatcs is Required
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Data growth is exponential
Difficult to understand life without BI
Detection of new diseases
BI tools allow to save expr. Expend.
Rational Drug design
Computer-aided vaccine design
GOLD:Genome Online Database
Published Complete Genomes: 93
- 16 Archaeal
- 65 Bacterial
- 12 Eukaryal
On-going:
- Prokaryotes: 284
- Eukaryotes : 195
Last update: 17 June 2002 (14:39hrs)
Kyrpides, N. (1999) Bioinformatics 15, 773-774
wit.integratedgenomics.com/GOLD/
Growth of Swiss prot
Growth of PDB
Growth of ‘gene-driven’ research
Number of papers including the word "gene"
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One paper every five minutes
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Application of Bioinformatics
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Genome Annotation
Protein Structure Prediction
Proteomics
DNA Chip technology
Disease Diagnostics
Fingerprinting Technique
Drug/Vaccine Design
Genome Annotation
The Process of Adding Biology Information and
Predictions to a Sequenced Genome Framework
Protein Structures
Protein Structure Prediction
 Experimental Techniques
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X-ray Crystallography
NMR
 Limitations of Current Experimental Techniques
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Protein DataBank (PDB) -> 17000 protein structures
SwissProt -> 90,000 proteins
Non-Redudant (NR) -> 800,000 proteins
 Importance of Structure Prediction
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Fill gap between known sequence and structures
Protein Engg. To alter function of a protein
Rational Drug Design
Traditional Proteomics
 1D gel electrophoresis (SDS-PAGE)
 2D gel electrophoresis
 Protein Chips
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Chips coated with proteins/Antibodies
large scale version of ELISA
 Mass Spectrometry
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MALDI: Mass fingerprinting
Electrospray and tandem mass spectrometry
• Sequencing of Peptides (N->C)
• Matching in Genome/Proteome Databases
Fingerprinting Technique
 What is fingerprinting
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It is technique to create specific pattern for a given
organism/person
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To compare pattern of query and target object
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To create Phylogenetic tree/classification based on pattern
 Type of Fingerprinting
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DNA Fingerprinting
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Mass/peptide fingerprinting
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Properties based (Toxicity, classification)
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Domain/conserved pattern fingerprinting
 Common Applications
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Paternity and Maternity
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Criminal Identification and Forensics
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Personal Identification
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Classification/Identification of organisms
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Classification of cells
Bioinformatics Approach for Identification of
Vaccine Candidate
Identification of the vaccine candidates (Antigenic
Region) for designing subunit vaccine.
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Antigen degraded in peptides by proteasome
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MHC Molecule bind to antigenic peptide
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MHC+peptide to cell surface
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Prediction of Promiscuous MHC binding peptides.
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Prediction Method for T-Cell Epitopes.
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Molecular Mimicry
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Model Studies on HIV and M.tuberculosis
Drug Design based on Bioinformatics Tools
 Detect the Molecular Bases for Disease
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Detection of drug binding site
Tailor drug to bind at that site
Protein modeling techniques
Traditional Method (brute force testing)
Rational drug design techniques
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Screen likely compounds built
Modeling large number of compounds (automated)
Application of Artificial intelligence
Limitation of known structures
 Search of Target protein
 Search of Lead compound
Steps in Post-Genomics
Transcriptomics large-scale analysis of messenger RNAs; when,
where, and under what conditions genes are expressed.
Proteomics
study of protein expression in time and space, more
important than gene expression studies to whats actually happening in
the cell.
Structural genomics 3-D structures of one or more proteins from
each protein family, clues to function and biological targets for drug
design.
Knockout studies experimental method for understanding the function
of DNA sequences and the proteins they encode. Inactivate genes in
living organisms and monitor any changes, reveal the function of
specific genes. Majority of knockouts do not give null phenotype.
Comparative genomics DNA sequence patterns of humans and
well-studied model organisms, most powerful strategies for
identifying human genes and interpreting their function.
Business Opportunities in BI
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Software development
Web servers development
Train manpower in Field of BI
Database management
Rational Drug design
Develop Diagnostic kits
Assist user in Vaccine development
Consultant to Biotech Companies
THANK YOU!