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Aligning Kinases

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Aligning Kinases. Applying MSA Analysis to the CDK family. Building A Multiple Sequence Alignment. Potential Uses of A Multiple Sequence Alignment ?. chite ---ADKPKRPLSAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKD wheat --DPNKPKRAPSAFFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSE - PowerPoint PPT Presentation

Text of Aligning Kinases

  • Aligning KinasesApplying MSA Analysis to the CDK family

  • Building A Multiple Sequence Alignment

  • Potential Uses of A Multiple Sequence Alignment?

    chite ---ADKPKRPLSAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKDwheat --DPNKPKRAPSAFFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSEtrybr KKDSNAPKRAMTSFMFFSSDFRS----KHSDLS-IVEMSKAAGAAWKELGPmouse -----KPKRPRSAYNIYVSESFQ----EAKDDS-AQGKLKLVNEAWKNLSP ***. ::: .: .. . : . . * . *: *

    chite AATAKQNYIRALQEYERNGG-wheat ANKLKGEYNKAIAAYNKGESAtrybr AEKDKERYKREM---------mouse AKDDRIRYDNEMKSWEEQMAE * : .* . : ExtrapolationMotifs/PatternsPhylogenyProfilesStruc. PredictionMultiple Alignments Are CENTRAL to MOST Bioinformatics Techniques.

  • 1

    Organizing a Family GatheringThe CDK example

  • Choosing the Right SequencesSwisProtLitteratureOther Databases

  • Organizing the DataSRSPublic DataIGS DataAventisCDKGenecardManualAutomatic

  • Accessing the Data: The Fischer ServerFischer will ContainA collection of Flat filesA secure SRS serverFile Formats

    The server is a Technology PipelineCan be adapted in real timeCan be Transfered

  • Our CDK DataCDKs and CDK-likeProtein InformationFunctional FeaturesStructural Information

    Genomic InformationGenesVariantSNPs

  • Our MSA dataset29 amino acid sequences (CDKS and Aurora families, stemming from primary transcripts)2 isoforms of a cdk member 4 PDB structures : 1MUO (AUR A) 1BLX (CDK 6 ) 1b38 (CDK 2) 1H4L (CDK 5)

    Use of T-coffee release 1.78 with integration of the structure informations contained in pdb files

  • 2

    Aligning The Sequences

  • Building A Multiple Sequence AlignmentClustalWT-CoffeeMuscleHand EditingCombinationComparison

  • Using Structural Information3D-CoffeeStruct Vs StructSeq Vs StructThreadSuperposeSeq Vs SeqLocal Global

  • Method

  • Accessing the Methods:FischerPublic 3D-Coffee serverigs-server.cnrs-mrs.fr/TCoffee/

    FischerLatest version of T-CoffeeCustomised parametersCoktails of MSA methods

  • 3

    Dressing Up aMultiple Sequence Alignment

  • Feature Dressing-25 Binding site-20 Phospho-40 nsSNP-50 Splice SiteEscript

  • Feature Dressing

  • 4

    How Good Is The Alignment

    ????

  • T-Coffee CORE Evaluation

  • T-Coffee CORE Evaluation

    CORE indexSpecificity () and Sensitivity ()

  • Feature Based Evaluation

  • Features mapping on multiple alignmentT-coffeeClustalW

  • Structure Based EvaluationAPDB

  • Structure Based EvaluationAPDB

  • Structure Based EvaluationAPDB

    Include Sequences with Known StructuresDo Not use Structural Information Score 1Use Structural Information:Score 2

    If Score1 ~ Score 2Structural Information does not help muchThe alignment is of reasonnable quality

  • Evaluating a Multiple Sequence AlignmentT-Coffee CORE indexFeature Based LibraryAPDB

  • Maninupulating and Comparing AlignmentsReformating/Processingseq_reformatextract_from_pdb

    Coloringseq_reformatESCript

    Comparingaln_compare

  • 5

    Thinking Large

    ????

  • T-Coffee_dpaT-Coffee is limited to a small number of sequences

    T-coffee_dpa: Double Progressive AlgoAble to handle large datasets1000 sequences and more

    Able to use structural information

  • Using A Multiple Sequence Alignment

  • 1

    Exploring The Alignment

  • Exploring The Alignment

  • 2

    Using The Alignment

    Does my Sequence Make Sense

  • Identifying Abnormalities within an MSA

  • Identifying Abnormalities within an MSA

  • Identifying Abnormalities within an MSA

  • Identifying Abnormalities within an MSAActivation loop (orange)

  • Identifying Abnormalities within an MSARetinoblastoma

  • 2

    Using The Alignment

    Analysing the Structure withThe Alignment

  • The Evoltionnary Trace

  • 3

    Using The Alignment

    Spotting differences

  • What makes a CDK not and AurorA

  • 4

    Clustering and Correlating

  • Function Trees Vs Lead Trees1-Select Functionnaly Important Positions2-Make a tree based on these positions3-Compare the tree with the lead tree

    PROBLEMS:Choose on the right positionsDescribe the Leads with the right determinants

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