138. Optical Genome Mapping workflow for identification and analysis of variants in Hematological Malignancies

Aly Abdelkareem

James Yu

James (Hung-Chun) Yu is a Senior Clinical Affair Scientist at Bionano Genomics. 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 and other disease populations. In pediatrics genetics, he analyzed patients with rare genetic disorders, and developed pediatric product related to healthy children screening. In HLI’s flagship healthy adult screening 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 Genomics.


James Yu, Hayk Barseghyan, Jen Hauenstein, Andy Pang, Alka Chaubey, Alex Hastie

Bionano Genomics, San Diego, CA, USA

Clinical guidelines for hematological malignancies include structural variation (SV) analysis as part of the genetic analysis. Currently, this requires a combination of three cytogenetic technologies: karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) to detect copy number variants, translocations, inversions, and other rearrangements. Next generation sequencing is also applied for small variant analysis but not successfully used for comprehensive SV analysis. Optical genome mapping (OGM) consolidates these cytogenetic techniques into a single assay capable of detecting all important genomic structural abnormalities. Furthermore, OGM detects cryptic SVs in a significant portion of cases and results in change interpretation of the biology underlying the malignancy in many cases.

OGM is able to comprehensively detect variants down to 5% variant allele fraction from blood, bone marrow aspirates, and tumor biopsies, making it an ideal choice for oncology clinical research. Preanalytical and analytical steps require approximately 3-5 days from input sample to analyzed results. Dynamic filtering in OGM software can remove most polymorphic variants and prioritize relevant variants. In addition, it allows assignment of classification to variants and multiple user level review process (e.g. preliminary analysis by lab scientist and final review by lab supervisor). For example, an ALL case with t(9;22), deletion of CDKN2A, and whole chromosome gains of 4,6, and 10 can be easily visualized and then further examined and classified as needed.

A variety of cases with hallmark abnormalities from various leukemias is presented here. This comprehensive technology allows for a quicker, more reliable output than traditional cytogenetic approaches.