2. Opportunities in Bioinformatics Presented By Dr G. P. S. Raghava Co-ordinator, Bioinformatic Centre IMTECH, Chandigarh Email: raghava@imtech.res.in Web: http://imtech.res.in/raghava/

3. 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)

4. 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

5. Relationships between sequence 3D structure protein functions Properties and evolution of genes, genomes, proteins, metabolic pathways in cells Use of this knowledge for prediction, modelling, and design Core of Bioinformatics TDQAAFDTNIVTLTRFVM EQGRKARGTGEMTQLLNS LCTAVKAISTAVRKAGIA HLYGIAGSTNVTGDQVKK LDVLSNDLVINVLKSSFA TCVLVTEEDKNAIIVEPE KRGKYVVCFDPLDGSSNI DCLVSIGTIFGIYRKNST DEPSEKDALQPGRNLVAA GYALYGSATML V

6. In 1995, the number of genes in the database started to exceed the number of papers on molecular biology and genetics in the literature! (Boguski, 1999) The challenge

7. More About Bioinformatics Sequence Analysis Database Homology Searching Multiple Sequence Alignment Homology Modeling Docking Protein Analysis Proteomics 3D Modeling Sample Registration & Tracking Integrated Data Repositories Common Visual Interfaces Intellectual Property Auditing Bio Informatics Genome Mapping

8. Computational Biology in the High-Throughput Era The Genome and Beyond n Scientific Challenges n Algorithmic Challenges n Computational Challenges

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

10. Media Hype and Confusion n Anybody can do BI n BI can do anything n Colleges/Courses/Training n No Quality Check n Limited Knowledge of Subject n More user than developer

11. Why Bioinformatcs is Required n Data growth is exponential n Difficult to understand life without BI n Detection of new diseases n BI tools allow to save expr. Expend. n Rational Drug design n Computer-aided vaccine design

14. Application of Bioinformatics n Genome Annotation n Protein Structure Prediction n Proteomics n DNA Chip technology n Disease Diagnostics n Fingerprinting Technique n Drug/Vaccine Design

15. Genome Annotation The Process of Adding Biology Information and Predictions to a Sequenced Genome Framework

16. Protein Structures

17. Protein Structure Prediction n Experimental Techniques –X-ray Crystallography –NMR n Limitations of Current Experimental Techniques –Protein DataBank (PDB) -> 17000 protein structures –SwissProt -> 90,000 proteins –Non-Redudant (NR) -> 800,000 proteins n Importance of Structure Prediction –Fill gap between known sequence and structures –Protein Engg. To alter function of a protein –Rational Drug Design

18. Traditional Proteomics n 1D gel electrophoresis (SDS-PAGE) n 2D gel electrophoresis n Protein Chips –Chips coated with proteins/Antibodies –large scale version of ELISA n Mass Spectrometry –MALDI: Mass fingerprinting –Electrospray and tandem mass spectrometry n Sequencing of Peptides (N->C) n Matching in Genome/Proteome Databases

19. Overview of 2D Gel n SDS-PAGE + Isoelectric focusing (IEF) –Gene Expression Studies –Medical Applications –Sample Experiments n Capturing and Analyzing Data –Image Acquistion –Image Sizing & Orientation –Spot Identification –Matching and Analysis

20. Comparision/Matcing of Gel Images n Compare 2 gel images –Set X and y axis –Overlap matching spots –Compare intensity of spots n Scan against database –Compare query gel with all gels –Calculate similarity score –Sort based on score

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

23. Differential Proteomics: Fingerprints of Disease PhenotypicChangesPhenotypicChanges Normal Cells Disease Cells Differential protein expression Protein nitration patterns Altered phosporylation Altered glycosylation profiles Differential protein expression Protein nitration patterns Altered phosporylation Altered glycosylation profiles Utility Target discovery Disease pathways Disease biomarkers Utility Target discovery Disease pathways Disease biomarkers

24. Fingerprinting Technique n 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 n Type of Fingerprinting –DNA Fingerprinting –Mass/peptide fingerprinting –Properties based (Toxicity, classification) –Domain/conserved pattern fingerprinting n Common Applications –Paternity and Maternity –Criminal Identification and Forensics – Personal Identification –Classification/Identification of organisms –Classification of cells

25. Drug Design based on Bioinformatics Tools n 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) n Rational drug design techniques –Screen likely compounds built –Modeling large number of compounds (automated) –Application of Artificial intelligence –Limitation of known structures n Search of Target protein n Search of Lead compound

26. History of Bioinformatics in India n Biocomputing started in 1950’s –IISc Banglore (Prof G Ramachandran) –Mostly analysis of protein structure n 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)

27. Education in Bioinformatics n 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 n Private Sector –Number of courses initiated –Dedicated training centers n Universities n R&D Institutes –Ph.D in Bioinformatics (IMT)

28. Business Comparisons CompanyRevenuesIT BudgetPct Bristol-Myers Squibb15,065,000,000440,000,0002.92 %Pfizer11,306,000,000300,000,0002.65 %Pacific Gas & Electric10,000,000,000250,000,0002.50 %K-Mart31,437,000,000130,000,0000.41 %Wal-Mart104,859,000,000550,000,0000.52 %Sprint14,235,000,000873,000,0006.13 %MCI18,500,000,0001,000,000,0005.41 %United Parcel22,400,000,0001,000,000,0004.46 %AMR Corporation17,753,000,0001,368,000,0007.71 %IBM75,947,000,0004,400,000,0005.79 %Microsoft11,360,000,000510,000,0004.49 % Chase-Manhattan16,431,000,0001,800,000,00010.95 % Nation’s Bank17,509,000,0001,130,000,0006.45 %

29. 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 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

30. 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 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

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

32. Business Opportunities in BI n Software development n Web servers development n Train manpower in Field of BI n Database management n Rational Drug design n Develop Diagnostic kits n Assist user in Vaccine development n Consultant to Biotech Companies

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

34. THANK YOU!