Opportunities in Bioinformatics

Presented By Dr G. P. S. RaghavaDr G. P. S. RaghavaCo-ordinator, Bioinformatic CentreCo-ordinator, Bioinformatic CentreIMTECH, ChandigarhIMTECH, Chandigarh

Email: raghava@imtech.res.inEmail: raghava@imtech.res.inWeb: 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

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