Methylation profile analysis using HMMs

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Methylation profile analysis using HMMs

  1. 1. A STATISTICAL MODEL FOR METHYLATIONLEVEL INFERENCE USING BS-SEQ DATAM. BESSOUL, G.VIEJO | Université Pierre et Marie Curie | 2012M A S T E RBIOINFORMATIQUEE T MODELISATIONdimanche 17 juin 2012
  2. 2. I. Background on DNA methylationII. MotivationsIII. BS-SeqIV. Data simulationV. Statistical modelVI. MethSeqVII. ResultsVIII. DiscussionCONTENTdimanche 17 juin 2012
  3. 3. CH3CH3CH3CH3CH3CH3I. DNA METHYLATIONDNMt...the CH3 group binds tothe C of a CpGdimanche 17 juin 2012
  4. 4. DNAPolymeraseAAAGATATAACGAGCATGCTAACCGTAATAAGCAGTCATGCA...DNAtranscriptionTarget genePromoter region(CpG rich)I. DNA METHYLATIONAND GENE SILENCING EFFECT.dimanche 17 juin 2012
  5. 5. DNAPolymerase transcriptionAAAGATATAACGAGCATGCTAACCGTAATAAGCAGTCATGCA...DNAAAAGATATAACGAGCATGCTAACCGTAATAAGCAGTCATGCA...DNAtranscriptionCH3 CH3CH3Target genePromoter region(CpG rich)I. DNA METHYLATIONAND GENE SILENCING EFFECT.dimanche 17 juin 2012
  6. 6. II. MOTIVATIONSDNAMethylated region0 1dimanche 17 juin 2012
  7. 7. III. BS-SEQG CCC T AmmG CTC T ASodiumbisulfite+PCRG CTC T ABISULFITE SEQUENCINGdimanche 17 juin 2012
  8. 8. III. BS-SEQG CCC T AmmG CTC T AG T ATT TSodiumbisulfite+PCRG CTC T AAlignmentBS Sequence over C-less referenceBISULFITE SEQUENCINGBisulfitesequenceC-lesssequencedimanche 17 juin 2012
  9. 9. III. BS-SEQALIGNMENTG CTC T AG T ATT Tdimanche 17 juin 2012
  10. 10. III. BS-SEQALIGNMENTC-less seqreadsG CTC T AG T ATT Tdimanche 17 juin 2012
  11. 11. III. BS-SEQALIGNMENTC-less seqreadsG CTC T AG T ATT TWhat do we get ? For every C position :•Number of overlapping reads :•Number of mismatches :yreadsycdimanche 17 juin 2012
  12. 12. IV. DATA SIMULATIONGENOME (.fasta file)Real profile(5mC positions)Short readsRandommethylationsimulationBisulfitetransformationBowtiealignmentSAM fileParsingBS-Seq data(coverage + mismatchesat C positions)SequencingC-less indexComparison.py script.py script.py scriptAlignmentand parsingDatasimulationdimanche 17 juin 2012

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