CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Project in Immunological Bioinformatics Morten Nielsen, CBS, BioCentrum, DTU.

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Presentation transcript:

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Project in Immunological Bioinformatics Morten Nielsen, CBS, BioCentrum, DTU

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Selection of epitopes Conservation Proteasome cleavage –Cleavage of C-terminus Tap binding MHC binding CTL binding/activation

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Prediction methods SYFPEITHI –Welcome to SYFPEITHIWelcome to SYFPEITHI Bimas –HLA Peptide Binding PredictionsHLA Peptide Binding Predictions

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU EasyPred Web interface for training of weight matrices and neural networks Weight matrices –Sequence weighting –Pseudo counts Neural networks –Hidden neurons –Splitting of Test/Training data –Cross validated training

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Weight matrices Is some pattern hidden in the sequences that binds MHC? –First step is to select peptides from the data pool that bind MHC –Next use the methods of sequences weighting and pseudo counts to estimate the weight matrix Evaluate the accuracy of the matrix on an independent data set.

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Evaluation of prediction accuracy True positive proportion = TP/(AP)False positive proportion = FP/(AN) A roc =0.5 A roc =0.8 Roc curves Pearson correlation TPFP AP AN

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU MHC peptide binding affinities Transformation o = 1 - log(aff nM)/log(50000) High binder aff < 50nM => o > Intermediate binder aff < 500nM => o > 0.426

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Test/Training performance Test max 20% 80% Test TRain

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU 5 fold test/training 20%

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Your favorite protein Swiss-Prot – Sars sequence –Sars entrySars entry

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Combination with Proteasomal cleavage Prediction of MHC binding 227 RLNQLESKV LLLDRLNQL ILLNKHIDA IVWVATEGA LLNKHIDAY GLPNNTASW YLGTGPEAS QIAQFAPSA QLQNSMSGA TTLPKGFYA QLPQGTTLP ELSPRWYFY TLLPAADMD ALNTPKDHI LLDRLNQLE TLPKGFYAE LLLLDRLNQ RLNQLESKV S..SS Netchop prediction server

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Project plan Follow the project description in detail Write down detailed notes as you go through the project Aflever kort resultat summery tirsdag d. 27. April (1-2 sider) kl 13.00