into to bioinfo

8/8/2019 Into to Bioinfo

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How Bioinformatics can change your lifeHow Bioinformatics can change your life

Basic Concepts of BioinformaticsBasic Concepts of Bioinformatics


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IntroductionIntroduction


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20002000

A Major event happened that was toA Major event happened that was tochange the course of human historychange the course of human history

It was a joint British and AmericanIt was a joint British and American

efforteffort It was a raceIt was a race who will completewho will complete

firstfirst

Race TestRace Test not whether they havenot whether they have

taken drugs but whether they cantaken drugs but whether they canproduce them!produce them!

Human genome was sequencedHuman genome was sequenced


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Bioinformatics is:Bioinformatics is:

driven by the generation of data,driven by the generation of data,moderated by hardware andmoderated by hardware andanalysis methodsanalysis methods

Computing power

Data generationplatforms

Analysis methods


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What isWhat is

The merging between computerThe merging between computerscience and molecular biologyscience and molecular biology The algorithm and techniques ofThe algorithm and techniques of

computer science are being used tocomputer science are being used to

solve the problems faced by molecularsolve the problems faced by molecularbiologistsbiologists

Information technology applied toInformation technology applied tothe management and analysis ofthe management and analysis ofbiological databiological data Storage and Analysis are two of theStorage and Analysis are two of the

important functionsimportant functions bioinformaticiansbioinformaticiansbuild tools for eachbuild tools for each


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Biology Chemistry

Statistics

ComputerScience

Bioinformatics


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What is..What is..

This is the age of the InformationThis is the age of the InformationTechnologyTechnology

However storing info is nothing newHowever storing info is nothing new

Information to the volume ofInformation to the volume ofBritannica Encyclopedia is stored inBritannica Encyclopedia is stored ineach of our cellseach of our cells

Bioinformatics tries to determineBioinformatics tries to determinewhat info is biologically importantwhat info is biologically important


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BasicsBasics

ofofMolecular Biology.Molecular Biology.


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DNA & GenesDNA & Genes

DNA is where the genetic information isDNA is where the genetic information isstoredstored

Blonde hair and blue eyes are inherited byBlonde hair and blue eyes are inherited bythisthis

GeneGene -- The basic unit of heredityThe basic unit of heredity There are genes for characteristics i.e. a geneThere are genes for characteristics i.e. a gene

for blond hair etcfor blond hair etc

Genes contain the information as aGenes contain the information as asequence of nucleotidessequence of nucleotides

Genes are abstract conceptsGenes are abstract concepts likelikelongitude and latitudes in the sense thatlongitude and latitudes in the sense thatyou cannot see them separatelyyou cannot see them separately

Genes are made up of nucleotidesGenes are made up of nucleotides


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Nucleotide (nt)Nucleotide (nt)

Each nt I made up ofEach nt I made up of SugarSugar Phospate groupPhospate group BaseBase

The base it (nt) contains makes the onlyThe base it (nt) contains makes the onlydifference between one nt and the otherdifference between one nt and the other There are 4 different basesThere are 4 different bases

G(uanine),A(denine),T(hymine),C(ytosine)G(uanine),A(denine),T(hymine),C(ytosine)

The information is in the order of nucleotideThe information is in the order of nucleotide

and the order is the infoand the order is the info Genes can be many thousands of nt longGenes can be many thousands of nt long The complete set of genetic instructions isThe complete set of genetic instructions is

called genomescalled genomes


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ProteinsProteins

Proteins are very importantProteins are very importantbiological featurebiological feature

Amino Acids make up the proteinsAmino Acids make up the proteins

20 different amino acids are there20 different amino acids are there The function of a protein isThe function of a protein is

dependant on the order of the aminodependant on the order of the aminoacidsacids


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ProteinsProteins

The information required to make aa isThe information required to make aa isstored in DNAstored in DNA

DNA sequence determines amino acidDNA sequence determines amino acidsequencesequence

Amino Acid sequence determines proteinAmino Acid sequence determines proteinstructurestructure Protein structure determines proteinProtein structure determines protein

functionfunction A Substance called RNA is used to carryA Substance called RNA is used to carry

theInfo stored in the

DNAthat in turn isthe

Info stored in the

DNAthat in turn isused to make proteinsused to make proteins

StorageStorage -- DNADNA Information TransferInformation Transfer RNARNA RNA is the message boy!RNA is the message boy!


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Central dogmaCentral dogma

DNADNA transcriptiontranscription RNARNA TranslationTranslation ProteinProtein

RNA PolymeraseRNA Polymerase RibosomesRibosomes


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Proteins..Proteins..

Since there are 20 amino acids toSince there are 20 amino acids totranslate one nt cannot correspondtranslate one nt cannot correspondto one aa, neither can it correspondto one aa, neither can it correspondas twosas twos

So in triplet codesSo in triplet codes codoncodon proteinproteininformation is carriedinformation is carried

The codons that do not correspondThe codons that do not correspond

to a protein are stop codonsto a protein are stop codons UAA,UAA,UAG, UGAUAG, UGA(RNA has U instead of T)(RNA has U instead of T)

Some codons are used as startSome codons are used as startcodonscodons -- AUG as well as to codeAUG as well as to code

methioninemethionine


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Protein StructureProtein Structure

Shows a wide variety as opposed to theShows a wide variety as opposed to theDNA whose structure is uniformDNA whose structure is uniform XX--ray crystallography orNuclear Magneticray crystallography orNuclear Magnetic

Resonance (NMR) is used to figure out theResonance (NMR) is used to figure out thestructurestructure

Structure is related to the function or ratherStructure is related to the function or ratherstructure determines the functionstructure determines the function Although proteins are created as a linearAlthough proteins are created as a linear

structure of aa chain they fold into 3 dstructure of aa chain they fold into 3 dstructure.structure.

If you stretch them and leave them they willIf you stretch them and leave them they willgo back to this structurego back to this structure this is thethis is the nativenativestructurestructure of a proteinof a protein

Only in the native structure the proteinsOnly in the native structure the proteinsfunctions wellfunctions well

Even after the translation is over proteinEven after the translation is over protein

goes through some changes to its structuregoes through some changes to its structure


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BioinformaticsBioinformaticsTechniques..Techniques..


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Prediction and PatternPrediction and PatternRecognitionRecognition

The two main areas of bioinformaticsThe two main areas of bioinformaticsareare

Pattern recognitionPattern recognition

A particular sequence or structure hasA particular sequence or structure hasbeen seen before and that a particularbeen seen before and that a particularcharacteristic can be associated with itcharacteristic can be associated with it

PredictionPrediction

From a sequence (what we know) weFrom a sequence (what we know) wecan predict the structure and functioncan predict the structure and function(what we dont know)(what we dont know)


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Dot plots.Dot plots.

Simple way of evaluatingSimple way of evaluatingsimilarity between twosimilarity between twosequencessequences

In a graph one sequence is onIn a graph one sequence is onone side the next on the otherone side the next on the othersideside

Where there are matchesWhere there are matchesbetween the two sequences thebetween the two sequences thegraph is markedgraph is marked


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AlignmentsAlignments

A match for similarity between the characters of two orA match for similarity between the characters of two ormore sequencesmore sequences

Eg.Eg. TTACTATATTACTATA TAGATATAGATA

There are so many ways to align the above twoThere are so many ways to align the above twosequencessequences 1.1.

TTACTATATTACTATA TAGATATAGATA

2.2. TTACTATATTACTATA TAGATATAGATA

3.3. TTACTATATTACTATA TAGATATAGATA

So which one do we choose and on what basis?So which one do we choose and on what basis? Solution is to Provide a match score and mismatch scoreSolution is to Provide a match score and mismatch score


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Dynamic ProgrammingDynamic Programming

As the length of the query sequencesAs the length of the query sequencesincrease and the difference of lengthincrease and the difference of lengthbetween the two sequence also increasesbetween the two sequence also increasesmore gaps has to be inserted in variousmore gaps has to be inserted in variousplacesplaces

We cannot perform an exhaustive searchWe cannot perform an exhaustive search

Combinatorial explosion occursCombinatorial explosion occurs too muchtoo muchcombinations to search forcombinations to search for

Dynamic programming is a way of usingDynamic programming is a way of usingheuristics to search in the most promisingheuristics to search in the most promisingpathpath


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DatabasesDatabases

Sequence info is stored inSequence info is stored indatabasesdatabases

So that they can be manipulatedSo that they can be manipulated

easilyeasily The db (next slide) are locatedThe db (next slide) are located

at diff placesat diff places

They exchange info on a dailyThey exchange info on a dailybasis so that they are upbasis so that they are up--toto--datedateand are in syncand are in sync

Primary dbPrimary db sequence datasequence data


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Nucleic acid (DNA/RNA)Nucleic acid (DNA/RNA)sequence databasessequence databases One main database arising from a partnershipOne main database arising from a partnership

between GenBANK at the NCBI (National Center forbetween GenBANK at the NCBI (National Center forBiotechnology InformationBiotechnology Information USA), the EMBL dataUSA), the EMBL datalibrary at the EBI (European Bioinformatics Institutelibrary at the EBI (European Bioinformatics Institute

UK) and the DNAData Bank at the NIG (NationalUK) and the DNAData Bank at the NIG (NationalInstitute of GeneticsInstitute of Genetics Japan).Japan).

Daily exchanges between the 3 partners to keep theDaily exchanges between the 3 partners to keep thedatabases synchronised.databases synchronised.

DNA and RNA sequences: curated, archived,DNA and RNA sequences: curated, archived,distributed.distributed.

Sequences from genome projects, scientific articles,Sequences from genome projects, scientific articles,patent applications. Most scientific journals requirepatent applications. Most scientific journals requireDNA and RNA sequences related to eachDNA and RNA sequences related to eachpublication to be publicly available.publication to be publicly available.

Sequences deposited early and going through aSequences deposited early and going through areview cycle; unannotated.. preliminary..review cycle; unannotated.. preliminary..unreviewed.. standard.unreviewed.. standard.

Format: human and computer readable.Format: human and computer readable.


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Major Primary DBMajor Primary DBNucleic AcidNucleic Acid ProteinProtein

EMBL (Europe)EMBL (Europe) PIRPIR --

Protein InformationProtein InformationResourceResource

GenBank (USA)GenBank (USA) MIPS,NCBIMIPS,NCBIDDBJ (Japan)DDBJ (Japan) SWISSSWISS--PROTPROT

University of Geneva,University of Geneva,now with EBInow with EBI

NCBINCBI TrEMBLTrEMBL

A supplement to SWISSA supplement to SWISS--PROTPROT

NRLNRL--3D3D


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Composite DBComposite DB

As there are many db which one toAs there are many db which one tosearch? Some are good in somesearch? Some are good in someaspects and weak in others?aspects and weak in others?

Composite db is the answerComposite db is the answer whichwhichhas several db for its base datahas several db for its base data

Search on these db is indexed andSearch on these db is indexed andstreamlined so that the same storedstreamlined so that the same storedsequence is not searched twice insequence is not searched twice indifferent dbdifferent db


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Composite DBComposite DB

OWL has these as their primaryOWL has these as their primarydbdb

SWISS PROT (top priority)SWISS PROT (top priority)

PIRPIR

GenBankGenBank

NRLNRL--3D3D


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Secondary dbSecondary db

Store secondary structure infoStore secondary structure infoor results of searches of theor results of searches of theprimary dbprimary db

CompoCompo

DBDB

PrimaryPrimary

SourceSource

PROSITEPROSITE SWISSSWISS--PROTPROT

PRINTSPRINTS OWLOWL


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Structural databasesStructural databases

The main database of protein structures is the PDBThe main database of protein structures is the PDB(Protein Data Bank).(Protein Data Bank).

The PDB started in 1971 at Brookhaven NationalThe PDB started in 1971 at Brookhaven NationalLabs (NY, USA) and is now a distributedLabs (NY, USA) and is now a distributed

organisation (Research Collaboratory for Structuralorganisation (Research Collaboratory for StructuralBioinformatics, www.rcsb.org) of US partnersBioinformatics, www.rcsb.org) of US partners(Rutgers, NJ; San Diego Supercomputer Centre,(Rutgers, NJ; San Diego Supercomputer Centre,Ca; NIST, Md).Ca; NIST, Md).

The PDB includes protein structures (and a fewThe PDB includes protein structures (and a fewDNA and other structures) determined by XDNA and other structures) determined by X--rayraycrystallography and Nuclear Magnetic Resonance.crystallography and Nuclear Magnetic Resonance.


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Database SearchesDatabase Searches

We have sequenced and identifiedWe have sequenced and identifiedgenes. So we know what they dogenes. So we know what they do

The sequences are stored inThe sequences are stored indatabasesdatabases

So if we find a new gene in theSo if we find a new gene in thehuman genome we compare it withhuman genome we compare it withthe already found genes which arethe already found genes which arestored in the databases.stored in the databases.

Since there are large number ofSince there are large number ofdatabases we cannot do sequencedatabases we cannot do sequencealignment for each and everyalignment for each and everysequencesequence

So heuristics must be used again.So heuristics must be used again.


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Areas inAreas in

BioinformaticsBioinformatics


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GenomicsGenomics

Because of the multicellular structure, eachBecause of the multicellular structure, eachcell type does gene expression in acell type does gene expression in adifferent waydifferent way although each cell has thealthough each cell has thesame content as far as the geneticsame content as far as the genetic

i.e.A

ll the information for a liver cell to be ai.e.A

ll the information for a liver cell to be aliver cell is also present on nose cell, soliver cell is also present on nose cell, sogene expression is the only thing thatgene expression is the only thing thatdifferentiatesdifferentiates


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GenomicsGenomics -- Finding GenesFinding Genes

Gene in sequence dataGene in sequence data needle in aneedle in ahaystackhaystack

However as the needle is differentHowever as the needle is differentfrom the haystack genes are not difffrom the haystack genes are not difffrom the rest of the sequence datafrom the rest of the sequence data

Is whole array of nt we try to find andIs whole array of nt we try to find andborder mark a set of nt as a geneborder mark a set of nt as a gene

This is one of the challenges ofThis is one of the challenges of

bioinformaticsbioinformatics Neural networks and dynamicNeural networks and dynamic

programming are being employedprogramming are being employed


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OrganismOrganism GenomeGenome

SizeSize

(Mb)(Mb)bp * 1,000,000bp * 1,000,000

GeneGene

NumberNumber

Web SiteWeb Site

YeastYeast 13.513.5 6,2416,241 http://genomehttp://genome--www.stanford.edwww.stanford.ed

u/Saccharomyceu/Saccharomycess

Fruit FliesFruit Flies 180180 13,60113,601 http://flybase.bio.http://flybase.bio.indiana.eduindiana.edu

HomoHomoSapiensSapiens

3,0003,000 45,00045,000 http://www.ncbi.nhttp://www.ncbi.nlm.nih.gov/genolm.nih.gov/genome/guideme/guide


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ProteomicsProteomics

Proteome is the sum total of anProteome is the sum total of anorganisms proteinsorganisms proteins

More difficult than genomicsMore difficult than genomics

44 2020 Simple chemical makeupSimple chemical makeup complexcomplex

Can duplicateCan duplicate cantcant

We are entering into the postWe are entering into the post

genome eragenome era Meaning much has been done withMeaning much has been done with

the Genesthe Genes not that its a overnot that its a over


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Proteomics..Proteomics..

The relationship between the RNA and the protein it codes areThe relationship between the RNA and the protein it codes areusually very differentusually very different

After translation proteins do changeAfter translation proteins do change So aa sequence do not tell anything about the postSo aa sequence do not tell anything about the post

translation changestranslation changes Proteins are not active until they are combined into a largerProteins are not active until they are combined into a larger

complex or moved to a relevant location inside or outside the cellcomplex or moved to a relevant location inside or outside the cell So aa only hint in these thingsSo aa only hint in these things Also proteins must be handled more carefully in labs as they tendAlso proteins must be handled more carefully in labs as they tend

to change when in touch with an inappropriate materialto change when in touch with an inappropriate material


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Protein Structure PredictionProtein Structure Prediction

Is one of the biggest challengesIs one of the biggest challengesof bioinformatics and esp.of bioinformatics and esp.biochemistrybiochemistry

No algorithm is there now toNo algorithm is there now toconsistently predict the structureconsistently predict the structureof proteinsof proteins


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Structure Prediction methodsStructure Prediction methods

Comparative ModelingComparative Modeling

Target proteins structure isTarget proteins structure iscompared with related proteinscompared with related proteins

Proteins with similar sequencesProteins with similar sequencesare searched for structuresare searched for structures


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PhylogeneticsPhylogenetics

The taxonomical system reflectsThe taxonomical system reflectsevolutionary relationshipsevolutionary relationships

Phylogenetics trees are things which reflectPhylogenetics trees are things which reflectthe evolutionary relationship thru athe evolutionary relationship thru a

picture/graphpicture/graph Rooted trees where there is only oneRooted trees where there is only one

ancestorancestor

Un rooted trees just showing theUn rooted trees just showing therelationshiprelationship

Phylogenetic tree reconstruction algorithmsPhylogenetic tree reconstruction algorithmsare also an area of researchare also an area of research


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Applications.Applications.


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Medical ImplicationsMedical Implications

PharmacogenomicsPharmacogenomics

Not all drugs work on all patients, some goodNot all drugs work on all patients, some gooddrugs cause death in some patientsdrugs cause death in some patients

So by doing a gene analysis before theSo by doing a gene analysis before thetreatment the offensive drugs can be avoidedtreatment the offensive drugs can be avoided

Also drugs which cause death to most can beAlso drugs which cause death to most can beused on a minority to whose genes that drug isused on a minority to whose genes that drug iswell suitedwell suited volunteers wanted!volunteers wanted!

Customized treatmentCustomized treatment

Gene TherapyGene Therapy

Replace or supply the defective or missing geneReplace or supply the defective or missing gene E.g: Insulin and Factor VIII or HaemophiliaE.g: Insulin and Factor VIII or Haemophilia

BioWeapons (??)BioWeapons (??)


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Diagnosis ofDiseaseDiagnosis ofDisease

Diagnosis of diseaseDiagnosis of disease Identification of genes which cause theIdentification of genes which cause the

disease will help detect disease at earlydisease will help detect disease at earlystage e.g. Huntington diseasestage e.g. Huntington disease --

SymptomsSymptoms uncontrollable dance likeuncontrollable dance like

movements, mental disturbance,movements, mental disturbance,personality changes and intellectualpersonality changes and intellectualimpairmentimpairment

Death in 10Death in 10--15 years15 years The gene responsible for the disease hasThe gene responsible for the disease has

been identifiedbeen identified


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Drug DesignDrug Design

Can go up to 15yrs andCan go up to 15yrs and$700million$700million

One of the goals ofOne of the goals of

bioinformatics is to reduce thebioinformatics is to reduce thetime and cost involved with it.time and cost involved with it.

The processThe process

DiscoveryDiscovery Computational methods canComputational methods can

improves thisimproves this

TestingTesting


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DiscoveryDiscovery

Target identificationTarget identification Identifying the molecule on which theIdentifying the molecule on which the

germs relies for its survivalgerms relies for its survival

Then we develop another moleculeThen we develop another moleculei.e. drug which will bind to the targeti.e. drug which will bind to the target

So the germ will not be able to interactSo the germ will not be able to interactwith the target.with the target.

Proteins are the most common targetsProteins are the most common targets


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DiscoveryDiscovery

For example HIV produces HIVFor example HIV produces HIVprotease which is a protein andprotease which is a protein andwhich in turn eat other proteinswhich in turn eat other proteins

This HIV protease has anThis HIV protease has an activeactivesitesite where it binds to otherwhere it binds to othermoleculesmolecules

So HIV drug will go and bindSo HIV drug will go and bindwith that active sitewith that active site


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DiscoveryDiscovery

Lead compounds are theLead compounds are themolecules that go and bind tomolecules that go and bind tothe target proteins active sitethe target proteins active site

Traditionally this has been a trialTraditionally this has been a trialand error methodand error method

Now this is being moved into theNow this is being moved into the

realm of computersrealm of computers


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Related ComputerRelated Computer

Technology.Technology.


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PERLPERL

Perl is commonly used forPerl is commonly used forbioinformatics calculations as itsbioinformatics calculations as itsability to manipulate characterability to manipulate charactersymbolssymbols

The default CGI languageThe default CGI language

It started out as a scripting languageIt started out as a scripting languagebut has become a fully fledgedbut has become a fully fledged

languagelanguage IT has everything now, even webIT has everything now, even web

service supportservice support

http://bio.perl.orghttp://bio.perl.org


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The place of XML & WebThe place of XML & WebServicesServices Various markup languages are being createdVarious markup languages are being created

Gene Markup language etc to representGene Markup language etc to representsequence/gene datasequence/gene data

Web ServicesWeb Services program to program interaction,program to program interaction,making the web application centric as opposed tomaking the web application centric as opposed tohuman centrichuman centric

So this has to platform language independentSo this has to platform language independent Protocols like SOAP help in this regardProtocols like SOAP help in this regard In bioinformatics various databases are being used,In bioinformatics various databases are being used,

different platforms, languages etcdifferent platforms, languages etc So web services helps achieve platformSo web services helps achieve platform

independence and program interactionindependence and program interaction Since sequence data bases are in various formats,Since sequence data bases are in various formats,

platforms SOAP also helps in this regardsplatforms SOAP also helps in this regards


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Data bases and MiningData bases and Mining

Lot of the sequence databases areLot of the sequence databases areavailable publiclyavailable publicly

As there is a DB involved variousAs there is a DB involved various

data mining techniques are used todata mining techniques are used topull the data outpull the data out

As there is a lot of literatureAs there is a lot of literature articlesarticlesetcetc on this area a data mining onon this area a data mining onthe literature.the literature.


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European Molecular BiologyEuropean Molecular BiologyNetwork (EMBnet)Network (EMBnet)

A central system for sharing, trainingA central system for sharing, trainingand centralizing up to date bio infoand centralizing up to date bio info

Some of the EMBnet sites are:Some of the EMBnet sites are:

SQENETSQENET http://www.seqnet.dl.ac.ukhttp://www.seqnet.dl.ac.uk

UCLUCL http://www.biochem.ucl.ac.uk/bsm/dbbrohttp://www.biochem.ucl.ac.uk/bsm/dbbro

wser/embnet/wser/embnet/ EBIEBI European BioinformaticsEuropean Bioinformatics

InstituteInstitute www.ebi.ac.ukwww.ebi.ac.uk


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ReferencesReferences

Dan E. Krane and Michael L. RaymerDan E. Krane and Michael L. Raymer

Basic Concepts of BioinformaticsBasic Concepts of Bioinformatics

Arthur M LeskArthur M Lesk

Intro to BioinformaticsIntro to Bioinformatics T.K. Attwood & D. J. ParryT.K. Attwood & D. J. Parry--SmithSmith

Intro to BioinformaticsIntro to Bioinformatics

The genetic RevolutionThe genetic Revolution

Dr Patrick DixonDr Patrick Dixon

ProfDavid Gilberts SiteProfDavid Gilberts Site

http://www.brc.dcs.gla.ac.uk/~drg/http://www.brc.dcs.gla.ac.uk/~drg/

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