Using ERDS to Infer Copy-Number Variants in High-Coverage Genomes

Abstract

Although there are many methods available for inferring copy-number variants (CNVs) from next-generation sequence data, there remains a need for a system that is computationally efficient but that retains good sensitivity and specificity across all types of CNVs. Here, we introduce a new method, estimation by read depth with single-nucleotide variants (ERDS), and use various approaches to compare its performance to other methods. We found that for common CNVs and high-coverage genomes, ERDS performs as well as the best method currently available (Genome STRiP), whereas for rare CNVs and high-coverage genomes, ERDS performs better than any available method. Importantly, ERDS accommodates both unique and highly amplified regions of the genome and does so without requiring separate alignments for calling CNVs and other variants. These comparisons show that for genomes sequenced at high coverage, ERDS provides a computationally convenient method that calls CNVs as well as or better than any currently available method.

Identification of Copy Number Variants Through Whole-Exome Sequencing in Autosomal Recessive Nonsyndromic Hearing Loss

“…We also noted that CoNIFER CNV analysis missed two heterozygous deletions used as positive controls. Recent CNV comparison studies in WES showed that by using the previously described heterozygosity check method (Zhu et al, 2012), CoNIFER detects less (40%) heterozygous false-positive deletions (for regions > 1 kb) compared to XHMM (64%) (Tan et al, 2014), suggesting that it might be missing some true positives to increase specificity. Conservative predefined thresholds in default settings of the CoNIFER might be the reason for missing heterozygous deletions in positive controls in our data set.…”

Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4–dependent mechanism

“…CNVs were called from WGS bam files using ERDS 10 and read Depth 11 . Overlapping calls with at least 90% reciprocity, less than 50% segmental duplications, and that were observed in five or fewer unaffected parents were retained.…”

Whole-Genome Sequencing in Pharmacogenetics

“…Once the reads are aligned, variants are inferred based on the differences between the test genome and the reference genome. At sufficiently high 'read depth' or 'coverage' of sequence, localized sharp increases or decreases in the depth of genomic coverage can accurately be inferred to represent duplications or deletions of DNA sequence, respectively [9]. These so-called 'structural variants' or 'copy number variants' have been shown to be of tremendous importance in terms of risk for some human diseases, and it is not unreasonable to suspect that this class of variants may also contribute substantially to variation in drug response; indeed, one of the most famous targets of pharmacogenetic studies, the CYP2D6 gene, exhibits a broad range of functional genetic variation that is explained to a significant extent by the number of intact copies of the gene across individuals [10].…”