Rshi Prarthana-Anargha Raghava, Uttara ramacharita & Vakyapadiyadraft
Opportunities in Bioinformatics Presented By Dr G. P. S. Raghava
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Transcript of Opportunities in Bioinformatics Presented By Dr G. P. S. Raghava
Opportunities in Bioinformatics
Presented By Dr G. P. S. RaghavaDr G. P. S. RaghavaCo-ordinator, Bioinformatic CentreCo-ordinator, Bioinformatic CentreIMTECH, ChandigarhIMTECH, Chandigarh
Email: [email protected]: [email protected]: http://imtech.res.in/raghava/Web: http://imtech.res.in/raghava/
What is Bioinformatics (BI) ?What is Bioinformatics (BI) ?
More About BioinformaticsMore About Bioinformatics
Historical Background Historical Background
Media Hype & ConfusionMedia Hype & Confusion
Important Applications of BIImportant Applications of BI
Bioinformatics in India Bioinformatics in India
Demand of BI ProfessionalsDemand of BI Professionals
How to Enter in BI (Course & How to Enter in BI (Course &
Degrees)Degrees)
What is BioinformaticsWhat is Bioinformatics
– Biocomputing: Application of Biocomputing: Application of Computer in BiosciencesComputer in Biosciences
– Biocomputing started in 1960’sBiocomputing started in 1960’s– Explosion of Genomic DataExplosion of Genomic Data– Access and Management of DataAccess and Management of Data– Biocomputing+Information ScienceBiocomputing+Information Science– Role of Internet in BIRole of Internet in BI
•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
TDQAAFDTNIVTLTRFVMEQGRKARGTGEMTQLLNSLCTAVKAISTAVRKAGIAHLYGIAGSTNVTGDQVKKLDVLSNDLVINVLKSSFATCVLVTEEDKNAIIVEPEKRGKYVVCFDPLDGSSNIDCLVSIGTIFGIYRKNSTDEPSEKDALQPGRNLVAAGYALYGSATMLV
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
More About BioinformaticsMore About Bioinformatics
SequenceAnalysis
DatabaseHomologySearching
MultipleSequence
Alignment
HomologyModelingDocking
ProteinAnalysis
Proteomics
3DModeling
SampleRegistration &
TrackingIntegrated
DataRepositories
CommonVisual
Interfaces
IntellectualPropertyAuditing
Bio Informatics
GenomeMapping
Computational Biology Computational Biology in the High-Throughput Erain the High-Throughput Era
The Genome and BeyondThe Genome and Beyond
Scientific ChallengesScientific Challenges Algorithmic ChallengesAlgorithmic Challenges Computational ChallengesComputational Challenges
Historical BackgroundHistorical Background Life Science - young compared to physics Life Science - young compared to physics
and chemistryand chemistry 1953 Structure of DNA1953 Structure of DNA 1960s Understanding of “code of life”1960s Understanding of “code of life” 1970s Genetic manipulation technology1970s Genetic manipulation technology 1980s Widespread innovation -1980s Widespread innovation -
biotechnology/genetic revolutionbiotechnology/genetic revolution 1990s Human Genome Project1990s Human Genome Project 2000s Structural Genomics ?2000s Structural Genomics ?
Media Hype and ConfusionMedia Hype and Confusion
Anybody can do BIAnybody can do BI BI can do anythingBI can do anything Colleges/Courses/TrainingColleges/Courses/Training No Quality CheckNo Quality Check Limited Knowledge of SubjectLimited Knowledge of Subject More user than developerMore user than developer
Why Bioinformatcs is Why Bioinformatcs is RequiredRequired
Data growth is exponentialData growth is exponential Difficult to understand life without BIDifficult to understand life without BI Detection of new diseasesDetection of new diseases BI tools allow to save expr. Expend.BI tools allow to save expr. Expend. Rational Drug design Rational Drug design Computer-aided vaccine designComputer-aided vaccine design
Application of Application of BioinformaticsBioinformatics
Genome AnnotationGenome Annotation Protein Structure PredictionProtein Structure Prediction ProteomicsProteomics DNA Chip technologyDNA Chip technology Disease DiagnosticsDisease Diagnostics Fingerprinting TechniqueFingerprinting Technique Drug/Vaccine Design Drug/Vaccine Design
Genome AnnotationGenome Annotation
The Process of Adding Biology Information andThe Process of Adding Biology Information and
Predictions to a Sequenced Genome FrameworkPredictions to a Sequenced Genome Framework
Protein StructuresProtein Structures
Protein Structure Protein Structure PredictionPrediction
Experimental TechniquesExperimental Techniques– X-ray Crystallography X-ray Crystallography – NMRNMR
Limitations of Current Experimental Limitations of Current Experimental TechniquesTechniques– Protein DataBank (PDB) -> 17000 protein structuresProtein DataBank (PDB) -> 17000 protein structures– SwissProt -> 90,000 proteinsSwissProt -> 90,000 proteins– Non-Redudant (NR) -> 800,000 proteinsNon-Redudant (NR) -> 800,000 proteins
Importance of Structure PredictionImportance of Structure Prediction– Fill gap between known sequence and structures Fill gap between known sequence and structures – Protein Engg. To alter function of a proteinProtein Engg. To alter function of a protein– Rational Drug DesignRational Drug Design
Traditional ProteomicsTraditional Proteomics
1D gel electrophoresis (SDS-PAGE)1D gel electrophoresis (SDS-PAGE) 2D gel electrophoresis2D gel electrophoresis Protein ChipsProtein Chips
– Chips coated with proteins/AntibodiesChips coated with proteins/Antibodies– large scale version of ELISAlarge scale version of ELISA
Mass SpectrometryMass Spectrometry– MALDI: Mass fingerprintingMALDI: Mass fingerprinting– Electrospray and tandem mass Electrospray and tandem mass
spectrometryspectrometry Sequencing of Peptides (N->C)Sequencing of Peptides (N->C) Matching in Genome/Proteome DatabasesMatching in Genome/Proteome Databases
Overview of 2D Gel Overview of 2D Gel SDS-PAGE + Isoelectric focusing (IEF)SDS-PAGE + Isoelectric focusing (IEF)
– Gene Expression StudiesGene Expression Studies– Medical Applications Medical Applications – Sample ExperimentsSample Experiments
Capturing and Analyzing DataCapturing and Analyzing Data– Image AcquistionImage Acquistion– Image Sizing & OrientationImage Sizing & Orientation– Spot IdentificationSpot Identification– Matching and AnalysisMatching and Analysis
Comparision/Matcing of Gel Comparision/Matcing of Gel ImagesImages
Compare 2 gel imagesCompare 2 gel images– Set X and y axisSet X and y axis– Overlap matching spotsOverlap matching spots– Compare intensity of spotsCompare intensity of spots
Scan against databaseScan against database– Compare query gel with all gelsCompare query gel with all gels– Calculate similarity scoreCalculate similarity score– Sort based on score Sort based on score
Mass FingerprintingMass Fingerprinting
Add protease (e.g. trypsin)Add protease (e.g. trypsin)– Get fragment size of peptidesGet fragment size of peptides
Scan against peptides of a protein Scan against peptides of a protein obtained theortically by that obtained theortically by that proteaseprotease
Scan against all proteomesScan against all proteomes
DNA Chip Technology
Differential Differential Proteomics:Proteomics:
Fingerprints of Fingerprints of DiseaseDisease
PhenotypicPhenotypicChangesChanges
PhenotypicPhenotypicChangesChanges
Normal CellsNormal Cells
Disease CellsDisease 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
Fingerprinting TechniqueFingerprinting Technique What is fingerprintingWhat is fingerprinting
– It is technique to create specific pattern for a given It is technique to create specific pattern for a given organism/personorganism/person
– To compare pattern of query and target objectTo compare pattern of query and target object– To create Phylogenetic tree/classification based on patternTo create Phylogenetic tree/classification based on pattern
Type of FingerprintingType of Fingerprinting– DNA FingerprintingDNA Fingerprinting– Mass/peptide fingerprintingMass/peptide fingerprinting– Properties based (Toxicity, classification)Properties based (Toxicity, classification)– Domain/conserved pattern fingerprinting Domain/conserved pattern fingerprinting
Common ApplicationsCommon Applications– Paternity and Maternity Paternity and Maternity – Criminal Identification and ForensicsCriminal Identification and Forensics– Personal Identification Personal Identification – Classification/Identification of organismsClassification/Identification of organisms– Classification of cellsClassification of cells
Drug Design based on Bioinformatics ToolsDrug Design based on Bioinformatics Tools
Detect the Molecular Bases for DiseaseDetect the Molecular Bases for Disease
– Detection of drug binding siteDetection of drug binding site
– Tailor drug to bind at that siteTailor drug to bind at that site
– Protein modeling techniquesProtein modeling techniques
– Traditional Method (brute force testing)Traditional Method (brute force testing)
Rational drug design techniquesRational drug design techniques
– Screen likely compounds built Screen likely compounds built
– Modeling large number of compounds (automated)Modeling large number of compounds (automated)
– Application of Artificial intelligenceApplication of Artificial intelligence
– Limitation of known structuresLimitation of known structures Search of Target proteinSearch of Target protein Search of Lead compoundSearch of Lead compound
History of Bioinformatics in IndiaHistory of Bioinformatics in India
Biocomputing started in 1950’sBiocomputing started in 1950’s– IISc Banglore (Prof G Ramachandran)IISc Banglore (Prof G Ramachandran)– Mostly analysis of protein structureMostly analysis of protein structure
Distributed information center (DIC)Distributed information center (DIC)– DBT initiate 9 DICs during 1986-7DBT initiate 9 DICs during 1986-7– National Facilities (IMT,IISc,IARI,JNU,MKU)National Facilities (IMT,IISc,IARI,JNU,MKU)– Sub-DICs started (around 50)Sub-DICs started (around 50)– Mirror sites in 1999 (IMT,Pune,JNU,IISc)Mirror sites in 1999 (IMT,Pune,JNU,IISc)
Education in BioinformaticsEducation in Bioinformatics Role of BIC’s in educationRole of BIC’s in education
– Workshops, training, course etc startedWorkshops, training, course etc started– Facilities/Infrastructure in BIFacilities/Infrastructure in BI– Advanced diploma in BI Advanced diploma in BI
(Pune,JNU,MKU)(Pune,JNU,MKU)– M.Sc. In bioinformaticsM.Sc. In bioinformatics
Private SectorPrivate Sector– Number of courses initiatedNumber of courses initiated– Dedicated training centersDedicated training centers
UniversitiesUniversities R&D InstitutesR&D Institutes
– Ph.D in Bioinformatics (IMT)Ph.D in Bioinformatics (IMT)
Business Business ComparisonsComparisonsCompany Revenues IT Budget Pct
Bristol-Myers Squibb 15,065,000,000 440,000,000 2.92 %
Pfizer 11,306,000,000 300,000,000 2.65 %
Pacific Gas & Electric 10,000,000,000 250,000,000 2.50 %
K-Mart 31,437,000,000 130,000,000 0.41 %
Wal-Mart104,859,000,000 550,000,000 0.52 %
Sprint 14,235,000,000 873,000,000 6.13 %
MCI 18,500,000,000 1,000,000,000 5.41 %
United Parcel 22,400,000,000 1,000,000,000 4.46 %
AMR Corporation 17,753,000,000 1,368,000,000 7.71 %
IBM 75,947,000,000 4,400,000,000 5.79 %
Microsoft 11,360,000,000 510,000,000 4.49 %
Chase-Manhattan 16,431,000,000 1,800,000,000 10.95 %
Nation’s Bank 17,509,000,000 1,130,000,000 6.45 %
Typical BioinformaticsMulti-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 BioinformaticsMulti-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 BioinformaticsMulti-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 BioinformaticsMulti-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
ExternalPublic
Databases
Bioinformatics ArchitectureBioinformatics Architecture
ExternalProprietaryDatabases
Unix servers
&SpecializedHardware
UsersWorkstation
Java & DesktopPrograms
WebBrowser
ActiveServer
Livewire CGINT
servers
ProprietaryInternal
Databases
WebServer
SharedAccess
Databases
MSAccess
Business Opportunities in BIBusiness Opportunities in BI
Software development Software development Web servers developmentWeb servers development Train manpower in Field of BITrain manpower in Field of BI Database managementDatabase management Rational Drug designRational Drug design Develop Diagnostic kitsDevelop Diagnostic kits Assist user in Vaccine developmentAssist user in Vaccine development Consultant to Biotech Companies Consultant to Biotech Companies
Bioinformatics at IMT, Bioinformatics at IMT, ChandigarhChandigarh
http://imtech.res.in/bic/ http://imtech.res.in/bic/ http://imtech.res.in/http://imtech.res.in/
Mirror Sites (http://www.imtech.res.in/mirror_sites/)Mirror Sites (http://www.imtech.res.in/mirror_sites/) Public Domain Resources in Biology (www.imtech.res.in/)Public Domain Resources in Biology (www.imtech.res.in/) IMTECH Library on Internet (/lib/)IMTECH Library on Internet (/lib/) Concept of vaccine design Concept of vaccine design Protein Structure Prediction (Olympic-2000)Protein Structure Prediction (Olympic-2000) Gene Prediction Gene Prediction Software for general useSoftware for general use
– GNU softwareGNU software– SUN FreewareSUN Freeware– PostgreSQLPostgreSQL
Site: Site: http//:imtech.res.in/raghava/www.htmlhttp//:imtech.res.in/raghava/www.html
THANK YOU!