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Eukaryotic Gene Prediction

Eukaryotic Gene Prediction. Rui Alves. Ryb. How are eukaryotic genes different?. DNA. mRNA. RNA Pol. Protein. mRNA. mRNA. mRNA. mRNA. Ryb. How are eukaryotic genes different?. DNA. RNA Pol. Spliceosome. Protein. Correctly Identifying Splicing sites is not a trivial task.

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Eukaryotic Gene Prediction

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  1. Eukaryotic Gene Prediction Rui Alves

  2. Ryb How are eukaryotic genes different? DNA mRNA RNA Pol Protein

  3. mRNA mRNA mRNA mRNA Ryb How are eukaryotic genes different? DNA RNA Pol Spliceosome Protein Correctly Identifying Splicing sites is not a trivial task

  4. How do we predict splicing sites? • By Homology • Ab initio • SS motifs • Codon usage • Exonic Splicing Enhancers • Intronic Splicing Enhancers • Exonic Splicing Silencers • Intronic Splicing Silencers

  5. Known Predicted spliced spliced gene gene Homology Splice Site Prediction

  6. Splice Site Motifs

  7. Exonic Splicing Enhancers

  8. Exonic Splicing Silencers Genes & Development 18:1241-1250

  9. Interaction between SE and SI

  10. Rules for Splicing 3’ end likely target for repression Distance between SE and 3’ end < 100bp Splicing efficiencyap(interaction SEC-3’ end)

  11. Methods for splicing detection Training set of know spliced genes Test set of know spliced genes Set of know spliced genes Algorithm GA, NN, HMM Bayes,ME GA, NN, HMM Bayesian Test set Predictions

  12. A Genetic Algorithm Method Shuffle lines and columns k times and each time calculate the probability of a given combination of motifs getting spliced Select m best combinations and continue to evolve the algorithm until it predicts training set

  13. A Neural Net Method Sequences Corrected Weight Table for splice elements Weight Table for splice elements Hidden Nodes Predicted Splicing

  14. Summary Eukaryotic genes have exons Biological rules combined with mathematical and statistical approaches can be used to predict the boundaries for the exons and to predict the splice variants

  15. How to find what genes a string of DNA contains Rui Alves

  16. Simple steps Go to a known gene prediction server (or google for one) Input sequence and wait for prediction Get prediction(s), either as cDNA or as a tranlated protein sequence and do homology searches to identify them in a known database (e.g. NCBI or SWISSPROT)

  17. Simple steps a) Go to a known gene prediction server (or google for one) Input sequence and wait for prediction Get prediction(s), either as cDNA or as a translated protein sequence and do homology searches to identify them

  18. Paper Presentation The human genome (Science) vs. The human genome (Nature) Nature : Pages 875 to 901 Science: Pages 1317-1337 Compare the differences in methods and results for the annotation DO NOT SPEND TIME TALKING ABOUT THE SEQUENCING OR ASSEMBLY ITSELF Do not go into the comparative genome analysis

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