MENU

PRINCESS: A Framework for Comprehensive Detection and Haplotype Phasing of SNPs and Structural Variants

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Baylor College of Medicine
    Biography
      Degree: Ph.D. in Biochemistry, Institute of Bioorganic Chemistry, Polish Academy of Science, Poznań, Poland.
      Postdoc fellow in Human Genome Sequencing Center, Baylor College of Medicine... Interests: I'm interested in studying genomic variants and their effect, including the development of tools for comprehensive variant analysis (SNVs, SVs, and Methylation).

    Abstract

    Long-read DNA sequencing technologies such as the Pacific Biosciences (PacBio) and Oxford Nanopore (ONT) platforms, have demonstrated enhanced detection of genomic variation, including Single Nucleotide Variants (SNVs), Structural Variants (SVs) and methylation changes. Individual studies so far have, however, have focused only on one of the three classes of variation: SNVs, SVs or methylation changes. Furthermore, only a few studies include phasing information to improve prediction of these classes of variation, to better associate genetic variation with phenotypes. Thus, clinical and research studies both currently lack a comprehensive view of genomic variation, even though the primary data is present in their DNA sequences. Here we introduce PRINCESS, a method that provides haplotype resolved SNVs, SVs and methylation changes based on a single long-read sequencing run from either PacBio or ONT. PRINCESS automatically adapts to different sequence coverage levels to optimally leverage the data set at hand. Thus, PRINCESS provides cost and time efficient comprehensive insights of haplotype resolved genomic variation. This information can be leveraged to simultaneous study the interaction of SNVs, SVs and methylation changes and their impact on phenotypic changes. PRINCESS was evaluated using Genome in a Bottle (GIAB) Oxford Nanopore standard and ultra-long reads as well as PacBio Continuous Long Reads (CLR) and Circular Consensus Sequencing (CCS) data. Using only one SMRT or PromethION flow cell Princess achieved high SNV precision (97.01%, 99.54%, 92.11%) and sensitivity (80.32%, 70.32%, 87.45%) for PacBio CLR, CCS and ONT PromethION, respectively, with minimum Genotype accuracy 98% of all read types. For SVs Princess also reached a high precision (93%, 94%, 86%) and a high sensitivity (77%, 79%, 79%). Both variant types were phased, achieving high N50s of 152Kbp, 117kbp and 17.42Mbp for PacBio CLR, CCS and ONT PromethION, respectively. We are currently evaluating methylation results from ONT. This highlights the versatility and performance of PRINCESS. PRINCESS applied to 18 PacBio with matching RNA-Seq data samples improved the detection of SVs (on average 22,105), SNVs and phasing (~5 Mbp average N50) and thus allowed the detection of eQTL in an automated, fast and comprehensive fashion.

    Learning Objectives:

    1. Princess: one-stop for all variant detection

    2. Comprehensive understanding of variations using long-reads (PacBio and Oxford Nanopore Technologies)

    3. Effect of CCS inserts size on Single Nucleotide and Structural Variation detection


    Show Resources
    You May Also Like
    OCT 08, 2020 7:00 AM PDT
    C.E. CREDITS
    OCT 08, 2020 7:00 AM PDT
    DATE: October 8, 2020 TIME: 7:00am PDT, 10:00am EDT, 4:00pm CEST How often do you pipette in your cell culture lab every day? Usually, we do it so often that we tend stop thinking about ho...
    NOV 16, 2020 8:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    NOV 16, 2020 8:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: November 16, 2020 Time: 8:00am (PST), 11:00am (EST) CRISPR screening has become the prime discovery tool in modern biomedical research and drug discovery. At the same time, most screen...
    OCT 29, 2020 6:00 AM PDT
    C.E. CREDITS
    OCT 29, 2020 6:00 AM PDT
    Date: October 29, 2020 Time: 6:00am (PDT), 9:00am (EDT), Chronic inflammation can occur as a result of a combination of genetic predispositions and environmental factors. Epigenetic modifica...
    NOV 10, 2020 7:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    NOV 10, 2020 7:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    DATE: November 10, 2020 TIME: 7:00am PDT, 10:00am EDT Automation can provide tremendous benefits such as increased pipetting precision and accuracy, productivity, and throughput. Numerous wo...
    SEP 10, 2020 9:00 AM PDT
    C.E. CREDITS
    SEP 10, 2020 9:00 AM PDT
    Date: September 10, 2020 Time: 9:00am (PDT), 12:00pm (EDT) Osmolality testing is relevant throughout the entire bioprocessing workflow. As customers look to refine mAb and gene therapy workf...
    AUG 25, 2020 8:00 AM PDT
    C.E. CREDITS
    AUG 25, 2020 8:00 AM PDT
    DATE: August 25, 2020 TIME: 8:00am PDT, 10:00am CDT, 11:00am EDT Recombinant lentivirus (LV) and adeno-associated virus (AAV) are critical components of cell and gene therapies, which show g...
    Loading Comments...
    Show Resources