Comparative analysis of hybrid-SNP microarray and nanopore sequencing for detection of copy-number variants in human cell lines

We performed whole-genome sequencing (WGS) with nanopore sequencing (NS) for copy number variant (CNV) calling in the acute myeloid (eosinophilic) leukemia (EOL-1) and B-cell precursor acute lymphoblastic leukemia (697) cell lines. Genomic DNA libraries were prepared using a rapid library preparation protocol and sequenced on the MinION device (Oxford Nanopore Technologies). NS data were processed using Guppy for basecalling, lra for read alignment, and CuteSV and Sniffles2 for variant calling. Mean coverage depths were of 13.1X for EOL-1 and 11.4X for 697. Simultaneously, chromosomal microarray analysis and CNV validation were performed on the same samples using array technology. We demonstrate that WGS with nanopore technology enables the identification of the majority of structural copy number variations detected by the gold-standard array method.