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Omixon   accurate variant detection slideshare version 2011 aug 17
 

Omixon accurate variant detection slideshare version 2011 aug 17

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This presentation describes some of our results in genomic variant detection. Using Omixon software we find variants not found by other software. We introduce a new short read mapping for Illumina, ...

This presentation describes some of our results in genomic variant detection. Using Omixon software we find variants not found by other software. We introduce a new short read mapping for Illumina, Ion Torrent and 454 for highly sensitive mapping and alignment especially for repeats. This is an excellent way to correct for homopolymer errors in 454 and Ion Torrent data. For a free download visit http://www.omixon.com/omixon/abouttoolkit2.htm .

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  • (double, triple substitutions, indels next to SNPs,10-30 bpindels, homopolymerindels, indels in palindromes, variants within GA repeats or TATA box)

Omixon   accurate variant detection slideshare version 2011 aug 17 Omixon accurate variant detection slideshare version 2011 aug 17 Presentation Transcript

  • Finding Novel Variants with Omixon Variant Toolkit
    Attila Berces, PhD
    CEO, Omixon
  • Omixon
    Bioinformatics
    Accurate variant analysis
    Cloud computing
    Usability
    • software products
    • cloud computing service
    • consultancy
  • Omixon – key people
    Science/technology
    Miklos Csuros, -
    professor University of Montreal, PhD from Yale University
    Tim Hague, BS Genetics, MSc System Design
    IBM, Lufthansa system
    Management
    Attila Bérces, PhD CEO,
    formerexecutive at AstraZeneca
    Lab head, Novartis
    S. George Simon,
    formerexecutivedirectoratMyriadGenetics
  • Late breaking development
    Omixon Read Mapper
    for Illumina, Ion Torrent and Roche
  • Omixon read mapper
    Scientific advances
    Sensitive handling of indels, especially tandem repeats
    Match/mismatch w/ local base composition
    Variable indexing density
    Letter space (Illumina, SOLiD5500, Roche, Ion Torrent)
    homopolymer error correction
  • Omixon read mapper
    User benefits
    Identify variants with more confidence
    higher coverage
    Identify difficult-to-find variants
    Save on consumables lower coverage
    Accurate read mapping at fast computational speed
  • Re-mapping validation
    Synthetic, 51 bpIllumina reads, experimental QVs
  • Sensitive handling of short repeats
  • Homo/hetero zygos double substitution
  • Four times exon coverage
    [0-96]
    BWA
    [0-432]
    Omixon
  • Higherexomecoverage
    [0-10]
    BWA
    [0-24]
    Omixon
  • Identify more valid variants
    BWA
    Omixon
  • Find homopolymerindels
    BWA
    Omixon
  • Why focus on variant analysis accuracy?
  • With scalable throughput and up to 99.99% accuracy, the SOLiD™ System enables you ……
  • Illumina sequencing systems, powered by TruSeq technology, deliver
    the most accurate data across a broad range of applications.
  • What is limiting the accuracy of variant analysis?
  • DNP example
    100 % accurate synthetic SOLiD v.4 reads reproducing naturally occurring DNPs
  • Found DNPs
    Bioscope: bioscope-v1.3-rBS131_55029_20101119113500; 
    BFAST 0.6.4f (2011-03-11); parameters: Clark MJ, Homer N, O'Connor BD, Chen Z,
    Eskin A, et al. PLoS Genet 6(1)
    SHRiMP 2.1.1b ( February 8, 2011) parameters: gmapper-cs -L database reads.csfasta
    -V -w 150% -n 1 -r 50% -v 55% -l 40% -Z -h 60% -a -1 (mapping in overly sensitive mode)
  • BFAST
    SHRiMP
  • … and with real data
  • Omixon
    Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • First conclusion
    Read accuracy is not the limiting factor in accurate variant analysis
  • Sanger validation
  • Visual inspection of short reads and variant calls
  • Sanger validation of inferred variants
    Omixon
    Omixon
    Omixon
    Omixon
    Omixon
  • Sanger validation of inferred variants
    Omixon
    Omixon
    Omixon
    Omixon
    Omixon
  • Second conclusion
    As variant density increases the performance of most tools go down
  • What types are the variants were only found by Omixon?
    DNPs
    TNPs
    Small indels, especially next to SNPs
    9-12 bpindels
    Homopolymerindels
    Homopolymerindel and SNP together
    Indels in palindromes
    Variants within GA repeats
    Pairwise substitution in TATA box
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Omixon
    Bioscope
    BFAST
    SHRiMP
  • Benefits of the Omixon plug-in for CLC bio workbench/server
  • Benefits of CLC bio plug-in
    Omixon
    CLC bio
  • Benefits of CLC bio plug-in
    Omixon
    CLC bio
  • Benefits of CLC bio plug-in
    Omixon
    CLC bio
  • Benefits of CLC bio plug-in
    Omixon
    CLC bio
  • Benefits of CLC bio plug-in
    Omixon
    CLC bio
  • Outstanding challenges
  • The sensitivity specificity challenge
  • How is Omixon different?
  • Sequencer-specific algorithms
    SOLiD
    Illumina
    SOLiD 5500
    Application-specific algorithms
    Exome-sequencing
    RNA-seq
    No sensitivity vs.specificitytrade-off
    Alignment based on DNA mutation model
  • Codon-based alignment
  • Please view our poster.
  • No Smith-Waterman
    No artifacts to correct downstream
    Quality values used in alignment
    Quality recalibration is the result not the input of the process
  • Our SOLiD Alignment Tools
    Csuros, Juhos, Berces "Fast Mapping and Precise Alignment of AB SOLiD Color Reads to Reference DNA" Springer Lecture Notes in Bioinformatics6293:176-188, 2010.
  • Computational Challenge
  • Conclusions
    There is no perfect method today for variant analysis but significant differences exist in accuracy
    OmixonVariant Toolkit provides highly sensitive and accurate analysis