Next generation Cytogenetics: Comprehensive Structural Analysis of Cancer Genomes by Optical Genome Mapping


Session type:


Ernest Lam1,Andy Peng2,Alex Hastie1,Yannick Delpu1
1Bionano Genomics,2Bionano Genomcis



Tumors are often comprised of heterogeneous populations of cells, with certain cancer-driving mutations at low allele fractions in early stages of cancer development. Effective detection of such variants is critical for diagnosis and targeted treatment. Conventional karyotype and cytogenetics approaches are manually intensive. Microarrays cannot detect calls in segmental duplications and repeats, often miss balanced variants, and have trouble finding low-frequency mutations. Typical short sequence reads are limited in their ability to span across repetitive regions of the genome and to facilitate structural variant (SV) analysis.


Based on specific labeling and mapping of ultra-high molecular weight (UHMW) DNA, we developed a single-molecule platform that has the potential to detect disease-relevant SVs and give a high-resolution view of tumor heterogeneity. We developed a DNA isolation and sample preparation workflow that preserves the DNA integrity and conserves structural variation information from blood, cells, and preserved tissue. Single molecules are labeled at specific motifs and analyzed in massively parallel nanochannels. The single-molecule maps are used in a bioinformatics pipeline that effectively detects structural variants at low allele fractions. It includes rare variant analysis and fractional copy number analysis.


Preliminary analyses using simulated and well-characterized cancer samples showed high sensitivity for variants of different types at as low as 5% allele fractions. The candidate variants are then annotated and further prioritized based on control data and publically available annotations. The data are imported into a graphical user interface tool that includes new visualization tools (such as Circos diagrams) for real-time interactive visualization and curation.


Bionano offers sample preparation, DNA imaging and genomic data analysis technologies combined into one streamlined workflow that enables high-throughput genome mapping on the Bionano Saphyr system. Together, these components allows for efficient analysis of any genome of interest from heterogenous samples.