Introduction

Complete knowledge of the genetic variation in individual human genomes is a crucial foundation for understanding the etiology of disease. Genetic variation is typically characterized by sequencing individual genomes and comparing reads to a reference. Existing methods do an excellent job of detecting variants in approximately 90% of the human genome; however, calling variants in the remaining 10% of the genome (largely low-complexity sequence and segmental duplications) is challenging. To improve variant calling, we developed a new algorithm, DISCOVAR, and examined its performance on improved, low-cost sequence data. Using a newly created reference set of variants from the finished sequence of 103 randomly chosen fosmids, we find that some standard variant call sets miss up to 25% of variants. We show that the combination of new methods and improved data increases sensitivity by several fold, with the greatest impact in challenging regions of the human genome.

Publications

  1. Comprehensive variation discovery in single human genomes.
    Cite this
    Weisenfeld NI, Yin S, Sharpe T, Lau B, Hegarty R, Holmes L, Sogoloff B, Tabbaa D, Williams L, Russ C, Nusbaum C, Lander ES, MacCallum I, Jaffe DB, 2014-12-01 - Nature genetics

Credits

  1. Neil I Weisenfeld
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  2. Shuangye Yin
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  3. Ted Sharpe
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  4. Bayo Lau
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  5. Ryan Hegarty
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  6. Laurie Holmes
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  7. Brian Sogoloff
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  8. Diana Tabbaa
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  9. Louise Williams
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  10. Carsten Russ
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  11. Chad Nusbaum
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  12. Eric S Lander
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  13. Iain MacCallum
    Developer

    -, Broad Institute of MIT and Harvard, United States of America

  14. David B Jaffe
    Investigator

    -, Broad Institute of MIT and Harvard, United States of America

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Summary
AccessionBT000348
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByDavid B Jaffe