Identification of copy number variants in whole-genome data using Reference Coverage Profiles

Frontiers in Genetics
Gustavo GlusmanLeroy Hood

Abstract

The identification of DNA copy numbers from short-read sequencing data remains a challenge for both technical and algorithmic reasons. The raw data for these analyses are measured in tens to hundreds of gigabytes per genome; transmitting, storing, and analyzing such large files is cumbersome, particularly for methods that analyze several samples simultaneously. We developed a very efficient representation of depth of coverage (150-1000× compression) that enables such analyses. Current methods for analyzing variants in whole-genome sequencing (WGS) data frequently miss copy number variants (CNVs), particularly hemizygous deletions in the 1-100 kb range. To fill this gap, we developed a method to identify CNVs in individual genomes, based on comparison to joint profiles pre-computed from a large set of genomes. We analyzed depth of coverage in over 6000 high quality (>40×) genomes. The depth of coverage has strong sequence-specific fluctuations only partially explained by global parameters like %GC. To account for these fluctuations, we constructed multi-genome profiles representing the observed or inferred diploid depth of coverage at each position along the genome. These Reference Coverage Profiles (RCPs) take into account the ...Continue Reading

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Citations

Jul 23, 2015·Journal of the American Medical Informatics Association : JAMIA·Arthur W TogaLeroy Hood
Jan 26, 2018·Molecular Genetics & Genomic Medicine·Natalie S HauserDale L Bodian
Jul 18, 2017·Nature Biotechnology·Nathan D PriceLeroy Hood
Jul 14, 2017·Cold Spring Harbor Molecular Case Studies·Dale L BodianNatalie S Hauser
Feb 16, 2018·Cold Spring Harbor Molecular Case Studies·Dale L BodianNatalie S Hauser
May 12, 2018·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Benjamin D SolomonJane Juusola
Jun 16, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ashleigh R PaveyBenjamin D Solomon

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