108. Optical genome mapping for detection of biomarkers in residual disease monitoring research of hematologic malignancies

Aly Abdelkareem

James Yu

James (Hung-Chun) Yu is a Senior Clinical Affair Scientist at Bionano Laboratories. James began studying chimpanzee chromosome 22 (chr22) for his doctoral degree at the University of Oklahoma, which later led to pursue of his post-doctoral research at the Children’s Hospital of Philadelphia (CHOP) focusing on human chr22 and related human disorders, such as DiGeorge syndrome. James later moved to University of Colorado, Anschutz Medical Campus where he continued his research on chr22 and started applying next-generation sequences (NGS) to identify novel disease-causing genes in pediatric rare diseases. He discovered a new type of cobalamin deficiency, cblX, caused by mutations in HCFC1 gene. His research also identified several new disease genes, including THAP11 (phenocopy of cblX), TMEM87B (cardiac defect), WDPCP (ciliopathy), CARS2 (mitochondria disease), and PMPCB (neurodegeneration disorder).

After his career in academics, James worked at Human Longevity, Inc. (HLI) using Whole Genome Sequencing (WGS) to investigate genetic risk in healthy adults, pediatric cases and other disease populations. In HLI’s flagship health program, Health Nucleus, James integrated WGS with advanced imaging, comprehensive metabolomics, and other clinical tests to provide insight into a person’s genetic risk in the era of precision medicine. His interests in genomic disorders and advanced technology bring him to his current position at Bionano Laboratories. James is a Clinical Affairs Scientist at Bionano Laboratories who collaborates with internal multidisciplinary teams and external clinical laboratories to perform clinical studies focusing on prenatal, postnatal, hematological malignancy, and solid tumors.


James Yu, Alex Chitsazan, Andy Pang, Alex Hastie

Bionano Laboratories, San Diego, CA, United States

Cancer disease monitoring and detection of biomarkers associated with relapse are critical for the appropriate therapeutic management of such diseases. Currently, karyotyping, fluorescent in situ hybridization (FISH), flow cytometry, PCR, and next-generation sequencing are often used for these applications. PCR is sensitive but it’s a targeted approach requiring identification of a biomarker. Karyotyping and FISH are used to detect structural variants (SVs); however, karyotype has low sensitivity and FISH is only targeted.

We describe a novel workflow using optical genome mapping (OGM) to find SVs as biomarkers used for disease monitoring research assessment. The initial SV profile can be obtained by running the standard somatic workflow: 1.5 Tbp of high molecular weight genomic DNA is collected and molecules capturing SV breakpoints are locally assembled into genome maps to make high-confidence SV calls at least 5 kbp in size. Then, presumptive somatic variants are revealed by comparison against an OGM control sample SV database. Subsequently, to detect residual cancer cells in follow-up specimens, two or more datasets can be rerun and biomarkers identified in the first sample can be used to search for residual cancer SVs. Through direct alignment of molecules to original biomarkers, we can detect biomarkers in 2-3% of cells, ~5x higher sensitivity compared to detection of biomarkers ab initio. This approach is fast and sensitive in identifying remnants of pretreatment originator cells. This is the first time OGM is applied for residual disease research monitoring and has demonstrated higher sensitivity compared to standard of care cytogenetic test.