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/