Next-Generation Mapping for Genome Assembly and Structural Variation Analysis

Next-generation mapping (NGM) from Bionano Genomics allows researchers to interrogate genomic structural variations (SVs) in the range of one kilobase pairs and above. It uses extremely long range information to span... [ view full abstract ]

Next-generation mapping (NGM) from Bionano Genomics allows researchers to interrogate genomic structural variations (SVs) in the range of one kilobase pairs and above. It uses extremely long range information to span interspersed and long tandem repeats making it suitable for elucidating the structure and copy number of complex regions of the human genome, such as loci with complex pseudogene and paralogous gene families. Because NGM is a de novo process and because molecules analyzed are longer than almost all genomic repeats, NGM is able to detect a wide range of SVs including insertions of novel sequence, tandem duplications, interspersed duplications, deletions, inversions and translocations, a range of SV types detectable by NGM alone. Because of the high speed and comprehensiveness of the SV types detected, NGM is increasingly being applied to the analysis of clinical genomes for the detection of SVs potentially involved in disease pathogenesis. We present several in silico and biological validation experiments to demonstrate the sensitivity and specificity of NGM for insertion, deletion and translocation SVs and compare it to benchmark studies using short read and long read sequencing. We also show the application of NGM to studying somatic variation in a breast cancer cell line, finding hundreds of somatic structural variations. Finally, we applied NGM to several leukemia patient samples to find more than 50 cancer related SVs in each patient. NGM is a fast and cost effective method for detection of a broad range of traditionally refractory SVs across the genome.