Whole Genome Analysis

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Whole Genome Analysis

  1. 1. Whole Genome AnalysisBone-Net Workshop - 21 January 2012 Ir Stéphane Wenric – s.wenric@dnavision.be
  2. 2. Whole Genome Analysis Whole genome analysis: why is it such a hot topic today?
  3. 3. Whole Genome Analysis
  4. 4. Whole Genome Analysis human whole genome sequencing Price Time
  5. 5. Whole Genome Analysis Microarray Exome Whole Genome Only known SNPs Only the coding regions The complete DNA (~ 900 000) of the genome sequencesUp to 0.0003 % of the ~ 1 % of the human ~ 80 % of the human human genome genome genome
  6. 6. Whole Genome Analysis What are the technologies involved ? • Illumina (Solexa) • ABI SOLiD • Ion Proton (2013)
  7. 7. Whole Genome Analysis Illumina (Solexa) : • cluster generation by bridge amplification • sequencing by synthesis
  8. 8. Whole Genome Analysis
  9. 9. Whole Genome Analysis ABI SOLiD : • amplification on magnetic beads • ligation + fluorescence detection • 2-base color encoding
  10. 10. Whole Genome Analysis
  11. 11. Whole Genome Analysis Ion semiconductor sequencing : • PCR amplification • dNTP incorporation w/ H+ release
  12. 12. Whole Genome Analysiswhole genome analysis = whole genome sequencing + bioinformatics
  13. 13. Whole Genome Analysis What kind of bioinformatics analyses are best suited for whole genome data? • SNP • Indels • CNV • SV
  14. 14. Whole Genome AnalysisSingle Nucleotide Polymorphisms • What? • How? • Impact?
  15. 15. Whole Genome Analysis
  16. 16. Whole Genome AnalysisSNPs : easy to detect 1. Map sequenced reads to reference sequence 2. See how the consensus sequence differs from the reference 3. 1-base difference between consensus sequence and reference = SNP
  17. 17. Whole Genome Analysis SNPs: impact? • Public databases: • DbSNP (ncbi) • OMIM (Johns Hopkins University School of Medicine) • SIFT (Craig Venter Institute) • … • Manual annotation
  18. 18. Whole Genome AnalysisInsertions and Deletions • What? • How? • Impact?
  19. 19. Whole Genome Analysis Insertion or deletion of a sequence of DNA of arbitrary length
  20. 20. Whole Genome Analysis Indels detection Small Indels : • Detection of small gaps in the alignment • Combination of the gapped alignments based on proximity • Filtering (read pos., coverage, quality) Large Indels : • Use of the reads pairing info (Illumina and SOLiD only)
  21. 21. Whole Genome Analysis Indels: impact? • Public databases: • dbSNP for small indels (ncbi) • dbVar for large indels (ncbi) • Manual annotation
  22. 22. Whole Genome AnalysisCopy Number Variations • What? • How? • Impact?
  23. 23. Whole Genome AnalysisCNV:• variation in terms of copy number of a sequence• >= 1 kb• up to n Mb
  24. 24. Whole Genome Analysis CNV detection methods • Statistical models: • Depth-of-reads/coverage • Pairing information
  25. 25. Whole Genome Analysis CNVs: impact? • Public databases: • Database of Genomic Variants (Center for Applied genomics, Canada) • CNV Project (Sanger) • ... • Manual annotation
  26. 26. Whole Genome AnalysisStructural Variations • What? • How? • Impact?
  27. 27. Whole Genome AnalysisStructural Variations • >= 1 kb • Inversions • Translocations • (Large indels) • (CNVs)
  28. 28. Whole Genome AnalysisInversions
  29. 29. Whole Genome AnalysisTranslocations
  30. 30. Whole Genome Analysis SVs: detection methods • Geometric approach (GASV) • Takes pairing info into account • Compares potential variants to geometric models
  31. 31. Whole Genome Analysis SVs: impact? • Public databases: • Database of Genomic Variants (Center for Applied genomics, Canada) • dbVar (ncbi) • ... • Manual annotation
  32. 32. Whole Genome Analysis Questions?

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