Electronic genome mapping (EGM) enables the direct detection of DNA-damaging endonuclease activity at the genome scale, according to research presented at the Advances in Genome Biology and Technology (AGBT) 2026 meeting.
Here, Barrett Bready, Founder & CEO of Nabsys, explains more about the study and its implications for diagnosis and treatment of age-related diseases.
What inspired this research?
Martin Taylor, Assistant Professor of Pathology and Laboratory Medicine at Brown University and Principal Investigator of the study, has been recognized as a pioneer in biomedical science. He is currently working to build an understanding of the human LINE-1 retrotransposon at the molecular level.
The LINE-1 retrotransposon has been referred to as “an ancient genetic parasite,” which uses a copy-and-paste mechanism to cause DNA damage and mutate the human genome. By leveraging transposon biology, Dr Taylor hopes to identify novel strategies for early diagnosis, prevention, and treatment of cancer, neurodegeneration, and other diseases of aging.
Using EGM technology, the researchers have a newfound ability to directly map this critical enzymatic activity genome-wide, revealing previously hidden genome instability caused by a LINE-1 endonuclease. This, in turn, unlocks new insights for human health.
What is EGM, in simple terms?
EGM is a fast, precise, and cost-effective genome mapping technology for high-resolution structural variant (SV) detection.
In the human genome, SVs are the largest source of genetic variation and have long been linked to both cancer and inherited disease. Traditional cytogenetics methods, as well as next-generation sequencing, struggle to reliably and efficiently identify SVs with resolution in the human genome. EGM provides new information from long DNA molecules that are difficult to analyze using other technologies.
It’s like taking a picture of a building, but your frame can only capture the size of a single brick. From that snapshot of a single brick, you try to guess the type of architecture of the actual building – in our case, the building is the genome. Today’s reliance on sequencing for whole genome analysis works in the same way as a camera that sees only the bricks in a building – without any context to the structure. This is mostly because sequencing looks so closely that it’s hard to pan out and see the structure of the entire genome. Without this view, whole-genome analysis is not complete, and much of the structure is missed.
EGM is an advanced, single-molecule nanodetection technology that uses electrical detection to map sequence-specific tags on long DNA molecules. Working at an unprecedented rate of 1 million base pairs (bp) per second, EGMs accurately sizes the intervals between tags on these long molecules. That information can be used to detect SVs in a sample.
The superior resolution comes from accurate detection of interval sizes as short as 300bp. This translates to a technology that can detect small SVs in the range of 300 bp, as well as very large SVs in the range of 100s to 1000s of kilobase pairs, and everything in between.
How does EGM enhance our understanding of the human genome?
EGM broadens the types of SV we can detect and therefore expands our ability to read the human genome. It helps researchers make new discoveries, understand disease causes, and ultimately open new avenues of research in constitutional disorders, hematological malignancies, and cell and gene therapies.
What is the significance to human health of the LINE-1 retrotransposon?
LINE-1 possesses endonuclease activity, allowing it to insert new copies of LINE-1 DNA into the genome – a process linked to cancer, age-related decline, and neurodegenerative disease, underscoring the importance of mapping its activity genome-wide.
ORF2p is a key, multifunctional enzyme encoded by the LINE-1 retrotransposon, a “copy and paste” genetic parasite. It has written around one-third of the human genome, and approximately five percent of humans harbor a new LINE-1 mediated genomic insertion that is not present in either parent.
What were the key findings of the study?
EGM provides a powerful tool to directly map endonuclease activity of the human LINE-1 ORF2p endonuclease genome-wide.
This technology enables the direct detection of endonuclease activity at the genome scale by identifying DNA nicking events on long DNA molecules. This capability addresses challenges associated with mapping endonuclease-induced nicks within complex DNA mixtures.
What is the potential impact of the findings on medical research?
By directly mapping the genomic sequences of LINE-1 endonuclease cuts, we gain a greater understanding of LINE-1-mediated DNA damage in cancer and insertional mutagenesis in sporadic genetic disease.
Simply put, we are making it easier to understand endonuclease activity at a genome-wide scale – paving the way to important research in genome editing and cell and gene therapy.
What do you anticipate as future applications of EGM?
EGM presents a whole-genome view of SV beyond what can be provided by current technologies. Future applications incorporate EGM as a critical tool for understanding constitutional disorders, hematological malignancies, and cell and gene therapies across both the research and clinical settings.
Let’s take cancer, for example. If you can identify the SV that has caused that cancer, then the doctor can target your therapy based on that specific SV, potentially improving prognosis. Thinking about inherited diseases, there may not be a disease-modifying therapy available, but there are still treatments that may be identified with an understanding of the SV in the patient’s genome. It’s game changing.
We also believe EGM is a powerful tool for directly measuring genome-scale DNA modifications with the potential to impact cell and gene therapy discovery and development significantly. Beyond endonuclease activity, future applications of EGM may enable direct, genome-wide analysis of additional DNA modifications and damage.
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