Opportunities in Bioinformatics

Presented By

Dr G. P. S. Raghava Co-ordinator, Bioinformatic Centre IMTECH, Chandigarh Email: [email protected]

Web: http://imtech.res.in/raghava/

What is Bioinformatics (BI) ?

More About Bioinformatics Historical Background Media Hype & Confusion Important Applications of BI Bioinformatics in India Demand of BI Professionals How to Enter in BI (Course & Degrees)

What is Bioinformatics

– – – – – – 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

Core of Bioinformatics

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Relationships between

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sequence 3D structure protein functions

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Properties and evolution of genes, genomes, proteins, metabolic pathways in cells

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Use of this knowledge for prediction, modelling, and design

The challenge

( Boguski, 1999 )

In 1995, the number of genes in the database started to exceed the number of papers on molecular biology and genetics in the literature!

More About Bioinformatics

Database Homology Searching Multiple Sequence Alignment Sequence Analysis Genome Mapping Protein Analysis Proteomics

Bio

Informatics

3D Modeling Homology Modeling Docking Sample Registration & Tracking Intellectual Property Auditing Integrated Data Repositories Common Visual Interfaces

Computational Biology in the High-Throughput Era

The Genome and Beyond    Scientific Challenges Algorithmic Challenges Computational Challenges

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Historical Background

Life Science - young compared to physics and chemistry 1953 Structure of DNA 1960s Understanding of “code of life” 1970s Genetic manipulation technology 1980s Widespread innovation biotechnology/genetic revolution 1990s Human Genome Project 2000s Structural Genomics ?

Media Hype and Confusion

      Anybody can do BI BI can do anything Colleges/Courses/Training No Quality Check Limited Knowledge of Subject More user than developer

Why Bioinformatcs is Required

      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

Application of Bioinformatics

       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 – X-ray Crystallography – NMR Limitations of Current Experimental Techniques – Protein DataBank (PDB) -> 17000 protein structures – – SwissProt -> 90,000 proteins Non-Redudant (NR) -> 800,000 proteins Importance of Structure Prediction – – 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 – – Chips coated with proteins/Antibodies large scale version of ELISA Mass Spectrometry – – MALDI: Mass fingerprinting Electrospray and tandem mass spectrometry  Sequencing of Peptides (N->C)  Matching in Genome/Proteome Databases

Overview of 2D Gel

  SDS-PAGE + Isoelectric focusing (IEF) – – – Gene Expression Studies Medical Applications Sample Experiments Capturing and Analyzing Data – – – – Image Acquistion Image Sizing & Orientation Spot Identification Matching and Analysis

Comparision/Matcing of Gel Images

  Compare 2 gel images – – – Set X and y axis Overlap matching spots Compare intensity of spots Scan against database – – – Compare query gel with all gels Calculate similarity score Sort based on score

Mass Fingerprinting

 Add protease (e.g. trypsin) – Get fragment size of peptides  Scan against peptides of a protein obtained theortically by that protease  Scan against all proteomes

DNA Chip Technology

Differential Proteomics: Fingerprints of Disease

Normal Cells

Phenotypic Changes

Disease Cells

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Differential protein expression Protein nitration patterns

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Altered phosporylation

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Altered glycosylation profiles Utility

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Target discovery

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Disease pathways

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Disease biomarkers

Fingerprinting Technique  What is fingerprinting – – – It is technique to create specific pattern for a given organism/person To compare pattern of query and target object To create Phylogenetic tree/classification based on pattern   Type of Fingerprinting – – – – DNA Fingerprinting Mass/peptide fingerprinting Properties based (Toxicity, classification) Domain/conserved pattern fingerprinting Common Applications – – – – – Paternity and Maternity Criminal Identification and Forensics Personal Identification Classification/Identification of organisms Classification of cells

Drug Design based on Bioinformatics Tools

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Detect the Molecular Bases for Disease

– – – Detection of drug binding site Tailor drug to bind at that site Protein modeling techniques – Traditional Method (brute force testing)

Rational drug design techniques

– – 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

History of Bioinformatics in India   Biocomputing started in 1950’s – – IISc Banglore (Prof G Ramachandran) Mostly analysis of protein structure Distributed information center (DIC) – – – – DBT initiate 9 DICs during 1986-7 National Facilities (IMT,IISc,IARI,JNU,MKU) Sub-DICs started (around 50) Mirror sites in 1999 (IMT,Pune,JNU,IISc)

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Education in Bioinformatics

Role of BIC’s in education – – – – Workshops, training, course etc started Facilities/Infrastructure in BI Advanced diploma in BI (Pune,JNU,MKU) M.Sc. In bioinformatics Private Sector – – Number of courses initiated Dedicated training centers Universities R&D Institutes – Ph.D in Bioinformatics (IMT)

Business Comparisons

Company Revenues IT Budget Pct

Chase-Manhattan 16,431,000,000 AMR Corporation 17,753,000,000 Nation’s Bank 17,509,000,000 1,130,000,000 Sprint 14,235,000,000 IBM 75,947,000,000 MCI 18,500,000,000 1,800,000,000 10.95 % 1,368,000,000 873,000,000 4,400,000,000 1,000,000,000 7.71 % 6.45 % 6.13 % 5.79 % 5.41 % Microsoft 11,360,000,000 United Parcel 22,400,000,000 510,000,000 1,000,000,000 4.49 % 4.46 % Bristol-Myers Squibb 15,065,000,000 Pfizer 11,306,000,000 Pacific Gas & Electric 10,000,000,000 Wal-Mart104,859,000,000 K-Mart 31,437,000,000 440,000,000 300,000,000 250,000,000 550,000,000 130,000,000 2.92 % 2.65 % 2.50 % 0.52 % 0.41 %

Typical Bioinformatics Multi-Disciplinary Training

•Scientists – Biology, Molecular Genetics, Clinical Biochemistry, Protein Structure Chemistry •Mathematicians – Statistics, Algorithms, Image processing •Computer Scientists – Database, User Interface/Visualizations, Networking (Internets/Intranets), Instrument Control

Typical Bioinformatics Multi-Disciplinary Functions

•Scientists – Experimental Design & Interpretation – Laboratory Protocols & Standards/Controls •Mathematicians – Analysis & Correlation of Data – Validation methodologies •Computer Scientists – Information Storage / Control Vocabulary – Data Mining

Bioinformatics Architecture

Users Workstation MS Access Web Browser Java & Desktop Programs NT servers Unix servers & Specialized Hardware Shared Access Databases Active Server Livewire CGI Web Server Proprietary Internal Databases External Public Databases External Proprietary Databases

Business Opportunities in BI

        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

Bioinformatics at IMT, Chandigarh

http://imtech.res.in/bic/ http://imtech.res.in/         Mirror Sites (http://www.imtech.res.in/mirror_sites/) Public Domain Resources in Biology (www.imtech.res.in/) IMTECH Library on Internet (/lib/) Concept of vaccine design Protein Structure Prediction (Olympic-2000) Gene Prediction Software for general use – – – GNU software SUN Freeware PostgreSQL Site: http//:imtech.res.in/raghava/www.html

THANK YOU!