Electronic Genome Mapping Reveals Structural Abnormalities in Hematologic Malignancies

Cytogenomic profiling is fundamental to characterizing hematologic malignancies, where detection of structural variants and copy number variants guides high‑resolution analysis. Standard cytogenetic testing and optical genome mapping are used to identify these abnormalities, but complex cases and smaller variants can be difficult to resolve comprehensively. Electronic approaches that analyze ultra‑long DNA may enable more detailed interrogation of genome structure. A new study shows how an electronic genome mapping platform performed against established methods in previously characterized leukemia samples.

Augusta University (Augusta, Georgia) researchers evaluated the Nabsys OhmX Platform implementing Electronic Genome Mapping (EGM) for cytogenomic analysis of hematologic malignancies. In a proof‑of‑principle design, the team examined previously characterized bone marrow aspirate specimens and compared EGM findings with karyotyping, fluorescence in situ hybridization (FISH), and optical genome mapping (OGM).

Image: The OhmX Platform uses electronic genome mapping to analyze ultra-long DNA molecules, combining electronic detection, nanofluidics, and computational biology in a compact system for high-resolution genome structure analysis. (Photo courtesy of Nabsys)

The OhmX Platform uses EGM to analyze ultra‑long DNA molecules electronically. Unlike traditional genome mapping systems that rely on lasers, cameras, and complex optics, EGM integrates electronic detection, nanofluidics, and computational biology in a compact system designed to deliver high‑resolution information about genome structure. According to Nabsys, the platform is research‑use‑only and is commercially available to laboratories worldwide.

The study included four acute myeloid leukemia (AML) samples and one chronic myeloid leukemia (CML) sample representing several classes of chromosomal abnormalities. EGM showed 100% concordance with standard cytogenetic testing and OGM for clinically relevant structural and copy number variants, detecting all pathogenic abnormalities identified by standard-of-care testing as well as the corresponding findings observed with OGM.

Detected abnormalities included BCR::ABL1 rearrangements; whole-chromosome changes such as trisomy 4, trisomy 21, and monosomy 7; deletions; and complex structural variants. EGM also resolved smaller alterations, including a KMT2A partial tandem duplication. In one complex AML case, the platform further characterized a chromosome 20 abnormality as an intrachromosomal fusion, confirmed 20q loss, and identified an approximately 1.8 Mb deletion at 7q22.1 that had not been reported by karyotyping or FISH.

The findings are available as a preprint on medRxiv under the title “Electronic Genome Mapping Enables High-Resolution Cytogenomic Profiling of Hematologic Malignancies: A Proof-of-Principle Study.”

"Our laboratory has extensive experience evaluating genome mapping in hematologic malignancies, and we were interested in understanding how an electronic approach would perform in well-characterized specimens. In this initial five-sample proof-of-principle study, EGM detected all of the abnormalities identified by standard cytogenetic testing and OGM while also providing additional structural information in complex cases. These results support further evaluation of EGM in larger and more diverse cohorts," said Ravindra Kolhe, M.D., Ph.D., FCAP, Professor and Chair of the Department of Pathology at Augusta University.

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