MAY 13, 2015 12:00 PM PDT

Dissecting the diagnostic yield of exome sequencing

Speaker
  • Senior Director, Genomics and Content, Personalis, Inc,
    Biography
      Deanna Church is the Senior Director of Genomics and Content at Personalis, Inc, a clinical genomics diagnostic company in Menlo Park, CA.She joined Personalis from the NCBI where she was one of the leads developing the GRCh38 reference and other bioinformatics databases. Deanna Church, Ph.D., was a staff scientist at NCBI, where she oversaw several projects concerning managing and displaying genomic data, including dbVar, a database of genomic structural variation, the NCBI Map Viewer, the Clone database, and the NCBI Remap service. Dr. Church is also a member of the Genome Reference Consortium (GRC) an international consortium charged with improving the human, mouse, and zebrafish assemblies, and was an author on the two seminal manuscripts describing the human and mouse genome sequences. She has experience in molecular biology, genetics, genomics, bioinformatics, and is currently focusing on making genomic data more useful through large-scale annotation and comparative genomics. She graduated from the University of Virginia with a BA in Liberal Arts in 1990, and received her doctoral degree in the Biological Sciences at the University of California, Irvine in 1997. She performed postdoctoral work with Dr. Janet Rossant at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto.

    Abstract

    Technological advances in high throughput, low cost DNA sequencing coupled with the availability of a high quality reference assembly allow us to interrogate the genome with greater precision than ever before. Together with increased understanding of the genetic underpinnings of disease, these advances mean our success rate in diagnosing genetic disease is increasing; yet the diagnostic yield of WGS/WES is only 25-50%. Improving this requires reexamination of the entire process, including assay development, bioinformatics analysis approaches as well as processes for robustly associating variants with disease. Assay development is critical as no single sequencing method can identify the spectrum of variant types nor can they access all regions of the genome equally. This becomes even more critical when testing for diseases that deviate from Mendelian expectations, such as cancer or diseases arising from somatic mosaicism. We are also learning that the reference assembly itself can have an impact on variant identification and interpretation. Our early, simplistic assembly models are insufficient for robust genome analysis and we must develop new models and analysis paradigms. Release of the latest reference assembly, GRCh38, is allowing us to identify several thousand variants calls that may actually be false positives due to missing sequence in GRCh37. This list includes pathogenic variants in ClinVar. Lastly, processes for understanding how detected variants may contribute to a particular disorder must be examined. Every person carries approximately 100 seemingly damaging variants, most of which do not contribute to rare disease. Clinical labs rely heavily on integrating large datasets from diverse resources such as the primary literature, OMIM, ClinVar, the 1000 Genomes project and the Exome aggregation browser. This integration is complicated by several factors, including inconsistent variant representation standards between the clinical and research community. Learning objectives: 1. The learner shall be able distinguish between different testing assays and understand how to evaluate assay performance. 2. The learner shall be able to describe how differences between the reference assembly and tested sample can affect variant identification.


    Show Resources
    You May Also Like
    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...
    NOV 16, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 16, 2020 8:00 AM PST
    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 18, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 18, 2020 8:00 AM PST
    DATE: November 18, 2020 TIME: 08:00am PDT We develop and implement technologies to solve some of the major bottlenecks in biomedical research. In particular, we establish new imaging approac...
    NOV 10, 2020 7:00 AM PST
    C.E. CREDITS
    NOV 10, 2020 7:00 AM PST
    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...
    FEB 24, 2021 10:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    FEB 24, 2021 10:00 AM PST
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    DATE: February 24, 2021 TIME: 10am PST Automated lab instruments such as liquid handlers and cell sorters are increasingly common in all types of laboratories, driving fast results for labor...
    MAY 13, 2015 12:00 PM PDT

    Dissecting the diagnostic yield of exome sequencing


    Specialty

    Antibodies

    Virology

    Immunology

    Dna Sequencing

    Personalized Medicine

    Clinical Diagnostics

    Immunity

    Cancer Diagnostics

    Immunotherapy

    Bioinformatics

    Flow Cytometry

    Immuno-Oncology

    Gene Expression

    Dna

    Big Data

    Geography

    Europe100%

    Registration Source

    Website Visitors100%

    Job Title

    Student100%

    Organization

    Academic Institution100%


    Show Resources
    Loading Comments...
    Show Resources
    Attendees
    • See more