109. Use of Bionano Optical Genome Mapping in a multi-platform structural variation analysis of a cancer reference cell line

Aly Abdelkareem

Alex Hastie

Alex Hastie has a PhD in Molecular and Cellular Biophysics and Biochemistry from Roswell Park Cancer Institute. He has received postdoctoral training in biochemistry at the Max Planck Institute for Biochemistry in Munich, Germany. He has spent over a decade with Bionano Genomics helping to design and develop core applications for optical genome mapping in genomics and epigenetics. Dr. Hastie is a lover of technology and believes that better genomics technology can improve the quality of life for people everywhere in the world.


Andy Wing Chun Pang, Ben Kellman, Alex Hastie, Alka Chaubey

Bionano Genomics, San Diego, CA, USA

Genomic structural variation (SV) analysis is fundamental to understanding cancer genetics, but its detection remains elusive. Standard-of-care tests such as karyotyping are low-throughput and labor-intensive, while chromosomal microarrays (CMA) cannot find copy-neutral events. Advances in sequencing and Bionano optical genome mapping (OGM) can address these shortcomings. The OGM workflow includes extraction of megabases-long DNA, labeling at specific motifs, and linearization in nanochannels for imaging. These molecules (>150kbp) are assembled or aligned to the human reference assembly to capture large SVs.

Here, we aim to generate a set of reference somatic SVs in a well-described matched breast tumor-normal cell line pair (HCC1395 and HCC13395BL) using multiple technologies and to compare their performance. The technologies used were Illumina, 10X Genomics, PacBio, Nanopore, Dovetail Hi-C, and Bionano OGM. CMA and PCR were used for validation.

Overall, SV sensitivity is dependent on technology used. While small SVs are consistent across platforms. SV calls >50kbp are the least discoverable, and OGM has the highest performance. Whereas smaller SVs called by OGM are more consistent with other platforms, suggesting that the platform is robust, large OGM calls are uniquely captured by ultra-long molecules. Bionano excelled at finding large DNA gains and fusion events – typical insertion is 2-orders of magnitude larger than others. Furthermore, Bionano uniquely called a ~40Mb somatic terminal 5q duplication.

Clinical genomic research requires SNV and SV analysis to comprehensively evaluate genomes, and this study shows that OGM is required to find all SV classes and that sequencing and OGM are complementary technologies.