Rapid, Reliable, and Interpretable Copy Number Variant Curation Visualizations for Diagnostic Settings with SeeNV.

Abstract

Copy number variants (CNVs), structural alterations in the genome involving duplication or deletion of DNA segments, are implicated in various health conditions. Despite their clinical significance, accurate identification and interpretation of CNVs remain challenging, especially in the context of whole-exome sequencing (WES), which is commonly used in clinical diagnostic laboratories. Although WES offers economic advantages over whole-genome sequencing, it struggles with CNV detection because of technical noise introduced by laboratory and analytic processes. Manual curation of CNV calls generated by these tools is labor intensive and error prone. To address this, SeeNV, a command-line tool, is introduced to aid manual curation of CNVs at scale. SeeNV is one solution to these issues, developed in collaboration with and used by the Precision Diagnostics Laboratory at Children's Hospital Colorado. SeeNV generates static infographics for each CNV, incorporating sample and cohort sequencing coverage statistics, CNV population frequency, and, more, facilitating rapid and precise assessment. Using CNV calls identified in publicly available WES and whole-genome sequencing samples, users can rapidly and reliably curate CNV calls, needing only 4.3 seconds to curate a call, achieving 0.95 recall (analytical sensitivity) and 0.74 precision (positive predictive value). SeeNV is freely available for download on GitHub.