New 3D genome mapping software reveals hidden complexity in DNA

October 29, 2025 – Standard laboratory checks can fail to detect many disease-causing DNA adjustments. Now, a novel 3D chromosome mapping technique can reliably reveal these hidden structural variants and result in new discoveries. The findings on this groundbreaking software might be present in a new study in The Journal of Molecular Diagnostics, printed by Elsevier, and are poised to rework diagnostic testing and therapy for genetic issues.

Traditional strategies sequence DNA in a linear, one-dimensional means, studying the genetic code as if it have been a flat line of textual content. In distinction, 3D chromosome mapping captures the spatial relationships between totally different components of the genome. It reveals how the lengthy strands of DNA fold and work together with one another within the three-dimensional area of the cell nucleus, which is significant for detecting sure structural adjustments which can be invisible to standard linear checks.

Researchers utilized genomic proximity mapping (GPM), a genome-wide Hi-C (high-throughput chromosome conformation seize sequencing)-based NGS assay, to DNA from 123 people with suspected genetic issues. This strategy captured the 3D contacts within the genome, which allowed the detection of each copy-number adjustments and rearrangements in DNA. GPM appropriately recognized all recognized giant chromosomal variants (110 deletions/duplications and 27 rearrangements) with 100% concordance. It additionally uncovered 12 novel structural variants that have been missed by normal scientific checks.

“We were excited by how much hidden complexity GPM revealed,” says co-lead investigator He Fang, PhD, Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle. “Using modern tools like GPM allows us to uncover hidden DNA rearrangements that standard tests miss. For example, one case with a known three-way translocation actually had 13 breakpoints across four chromosomes when mapped by GPM. In every patient with multiple rearrangements, GPM uncovered additional cryptic changes. It was also impressive that GPM detected low-level mosaic variants, or cells with different genetic makeup, with high sensitivity. These discoveries went beyond our expectations and highlight the power of this new method.”

Key outcomes of the examine are as comply with:

• 100% detection of recognized variants: GPM discovered all 110 beforehand recognized copy-number variants and 27 rearrangements within the cohort.
• High precision on complicated occasions: Breakpoints of each balanced and unbalanced rearrangements have been pinpointed to a excessive diploma of accuracy (inside ~10 kb), and GPM even labored on difficult samples like preserved tissue whereas detecting mosaic adjustments.
• New discoveries: GPM revealed 12 extra structural variants that normal strategies had missed.
• Hidden complexity: In each case that had a number of rearrangements by conventional checks, GPM discovered additional cryptic adjustments.

GPM requires considerably much less DNA than is usually wanted for standard cytogenetic strategies or rising applied sciences akin to optical genome mapping (OGM) and long-read sequencing (LRS), thereby enhancing its practicality for real-world scientific implementation.

Identifying the precise genetic rearrangement might open the door to focused therapies or scientific trials particular to these variants.

Co-lead investigator Yajuan J. Liu, PhD, Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, concludes, “GPM offers broad clinical benefits. It enables high-resolution, comprehensive genomic characterization, even from compromised samples such as low-quality or archived preserved tissue. As genomic medicine moves toward precision diagnostics, this new tool addresses current limitations in genetic testing, improving diagnostics and empowering doctors to provide personalized treatment, tailored monitoring, better prognosis, and improved family counseling.”