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Scope and Importance of Bioinformatics
Do you have required skill?
Type of bioinformaticians (Users, Analysis or Developer)
Possible biological problems
Protein/Peptide related bioinformatics
Types of methods and use of Open Source
How to start
Linux, programming (PHP/perl)
WAMP/LAMP (Linux/Windows, Apache, Mysql, PHP)
Machine learning techniques (Weka)
Beware with experimental biologist
Concept of Research in Bioinformatics
• Bioinformatics vs Computational Biology
• Service vs Research
• Components vs System Biology
• Guidelines/Suggestions
• Role of technical expertise
• Our group (Service or Science?)
Bioinformatics Vs Computational Biology
Computational Biology Examples• Ramachandran Plot• Proteins Structure Prediction (Ab-initio)• Dynamic Programming for Alignment
Examples of Bioinformatics• BLAST search against sequence databases• Homology Modelling• Epitope Mapping
Service Vs Bioinformatics Research• BTIS Programme• NCBI and EBI Services• Web service / databases
• New rules or models derived from known structures• New functional domain form experimental data• Discoveries based on data
• Service for better research• Research for better service• Range of service (Individual or Community)• Collaboration with experimental scientist for validation
Suggestions Selection of Problem
• Talk to biologist & understand their problem• Raise question in your mind• Read literature (self learning) for answer• Raise more question and read again• Work on important problem• Select problem if large dataset is availble• Develop method with high accuracy• Validate using standard validation techniques• Develop web server software for service• Publish in appropriate journal (high IF)
Assembling of Genomes
Whole genome Sequencing
Genome AnnotationAnotation of
Proteomes
Microarray Data
Subcellular Localization
FingerprintinFingerprinting Techniqueg Technique
Epitope based Epitope based VaccinesVaccines
Drug targetsDrug targets
Comparative Comparative GenomicsGenomics
Drug DiscoverDrug Discover
FingerprintinFingerprinting Techniqueg Technique
Development Development of Databsesof DatabsesRNA RNA
InterferenceInterference
Therapeutic Application of Proteins/Peptides
Peptide based Drugs (Small Molecule, Peptide, Protein)
• Anticancer peptides• Antibacterial peptides
Peptide for delivering drug • Cell-penetrating peptides• Tumor-homing peptides
Peptide as disease diagnostics• Disease specific Mimotopes
Epitope/Peptide based Vaccines• T-cell epitopes• B-cell epitopes
Limitation of Peptides & Challenges for Bioinformaticians
1. Peptide Degradation (short half-life)
• Large peptide degrading enzymes
• Hepatic/renal Clearance (liver/kidenys)
2. Low Oral Bioavailability (injection)
3. High conformational flexibility
• Environment dependent tertiary structure
• Low selectivity
4. Immunogenicity and antigenicity
5. High cost of production & Storage
• Modification/glycosylation of peptides
Peptide or Protein
Drug/inhibitor/vaccine/ Disease Diagnostics
Peptide Structure, docked structure
Peptide-Protein Interaction
Adaptive Immunity: B-cell, T-cell Epitope
Innate Immunity: Toll-like receptors
Anti-(bacterial , microbial, cancer, viral) peptides
Mimotopes for diseases diagnostics
Structure prediction: Natural, non-natural , modified bonds
Structure determination: Natural, non-natural , modified bonds
Synthesis: Phase display, SPSS, Codon Suffeling
Natural bioactive peptides from metagenomics
Mimotopes for B/T epitopes Mimicking of Drug Molecules
ADMET: Proteolytic enzymes, Half-life
Oral Delivery : Trans. & Adjuvant
Size Optimization for function/Str.
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
WHOLEORGANISM
Attenuated
Epitopes (Subunit Vaccine)
Purified Antigen
T cell epitope
Multiple layers of the immune system
Pathogens/Invaders
Disease Causing Agents
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
Components vs System Biology
Modelling of Immune System for Designing Epitope-based Vaccines
Adaptive Immunity (Cellular Response) : Thelper Epitopes
Adaptive Immunity (Cellular Response) : CTL Epitopes
Adaptive Immunity (Humoral Response) :B-cell Epitopes
Innate Immunity : Pathogen Recognizing Receptors and ligands
Signal transduction in Immune System
Propred: for promiscuous MHC II binders
MMBpred:for high affinity mutated binders
MHC2pred: SVM based method
MHCBN: A database of MHC/TAP binders and non-binders
Pcleavage: for proteome cleavage sites
TAPpred: for predicting TAP binders
Propred1: for promiscuous MHC I binders
CTLpred: Prediction of CTL epitopes
Cytopred: for classification of Cytokines
BCIpep: A database of B-cell eptioes; ABCpred: for predicting B-cell epitopesALGpred: for allergens and IgE eptopes
HaptenDB: A datbase of haptens
PRRDB: A database of PRRs & ligands
Antibp: for anti-bacterial peptides
Important Information in Manual for Develpers
Computer-Aided Drug DiscoverySearching Drug Targets: Bioinformatics
Genome AnnotationFTGpred: Prediction of Prokaryotic genesEGpred: Prediction of eukaryotic genesGeneBench: Benchmarking of gene findersSRF: Spectral Repeat finder
Comparative genomics GWFASTA: Genome-Wide FASTA Search GWBLAST: Genome wide BLAST search COPID: Composition based similarity search LGEpred: Gene from protein sequence
Subcellular Localization MethodsPSLpred: localization of prokaryotic proteinsESLpred: localization of Eukaryotic proteins
HSLpred: localization of Human proteinsMITpred: Prediction of Mitochndrial proteins
TBpred: Localization of mycobacterial proteins
Prediction of drugable proteinsNrpred: Classification of nuclear receptorsGPCRpred: Prediction of G-protein-coupled receptorsGPCRsclass: Amine type of GPCR VGIchan: Voltage gated ion channelPprint: RNA interacting residues in proteinsGSTpred: Glutathione S-transferases proteins
Protein Structure PredictionAPSSP2: protein secondary structure predictionBetatpred: Consensus method for -turns prediction Bteval: Benchmarking of -turns prediction BetaTurns: Prediction of -turn types in proteins Turn Predictions: Prediction of / / -turns in proteinsGammaPred: Prediction of-turns in proteins
BhairPred: Prediction of Beta Hairpins
TBBpred: Prediction of trans membrane beta barrel proteins
SARpred: Prediction of surface accessibility (real accessibility)
PepStr: Prediction of tertiary structure of Bioactive peptides
Suggestions Technical Learning • Linux/Unix system
• Programming language PERL/PHP/C• Example Scripts
(http://www.imtech.res.in/raghava/gpsr/ )• HTML and CGI script (Java)• LAMP learning• SVM_Light for SVM, SNNNS for ANN• TREMBL for nearest neighbour• Weka for wide range• Rapidminer
Important URLs
http://www.imtech.res.in/raghava/
http://www.imtech.res.in/raghava/gpsr/
http://www.imtech.res.in/raghava/reprints/
http://www.imtech.res.in/raghava/slides/
http://crdd.osdd.net/
http://crdd.osdd.net/raghava/ccpdb/