In October 2020, Praxis Genomics made a strategic decision that would define our diagnostic philosophy: we invested in Bionano's Saphyr optical genome mapping (OGM) system, becoming one of the earliest clinical adopters of this transformative technology.
The Vision: Beyond Sequence-Level Analysis
Traditional genetic testing has long focused on DNA sequence—identifying changes in individual nucleotides or small insertions and deletions. While whole exome and genome sequencing dramatically advanced rare disease diagnosis, a significant portion of patients remained undiagnosed.
The reason? Structural variants—large chromosomal rearrangements, balanced translocations, complex inversions, and copy number changes—were often invisible to sequencing technologies, yet they account for a substantial fraction of pathogenic variation.
Why Optical Genome Mapping?
Optical genome mapping represented a fundamentally different approach to analyzing genomes:
Long-Range Visualization
Unlike sequencing technologies that read short fragments and computationally reconstruct the genome, OGM directly images ultra-long DNA molecules (hundreds of thousands to millions of base pairs), providing a unique bird's-eye view of chromosomal structure.
Unbiased Genome-Wide Detection
OGM doesn't rely on prior knowledge of where to look—it scans the entire genome for structural variants in a single assay, detecting changes that might never be found through targeted or sequential testing approaches.
Resolution of Complex Variants
The technology excels at characterizing complex rearrangements that confound other methods—insertions within deletions, chromothripsis, and multi-break rearrangements that play critical roles in both constitutional disorders and cancer.
Early Results Validate the Bet
Our early clinical experience with OGM confirmed its value:
- Previously Unsolved Cases: We began identifying diagnoses in patients who had undergone extensive prior testing without answers
- Unexpected Findings: Complex structural variants appeared in cases where they weren't initially suspected
- Improved Characterization: Even when copy number changes were known from microarray, OGM provided precise breakpoint mapping and revealed unexpected complexities
The Multi-Platform Philosophy
Importantly, we didn't view OGM as a replacement for sequencing—we saw it as a powerful complement. This insight led to our current diagnostic approach:
- Optical Genome Mapping: For structural variant detection
- Whole Genome Sequencing: For sequence-level variant identification
- Transcriptome Analysis: For functional validation
By integrating these technologies from the start, we can detect nearly all types of genetic variation in a single comprehensive analysis.
Impact on the Field
Since our adoption of OGM, the technology has gained widespread recognition:
- Multiple validation studies have confirmed its clinical utility
- Leading academic medical centers have integrated OGM into their diagnostic workflows
- Professional guidelines increasingly recommend OGM for specific clinical indications
- The technology has expanded beyond constitutional disorders into cancer diagnostics and other applications
Looking Back, Moving Forward
Four years later, our bet on Bionano optical genome mapping has proven prescient. The technology has become central to our diagnostic success and has helped hundreds of families obtain answers after years of uncertainty.
More importantly, it reinforced a core principle: comprehensive genetic diagnosis requires multiple complementary technologies working in concert. No single method can capture the full spectrum of genetic variation—success requires integration, innovation, and a commitment to adopting new technologies even when they challenge conventional approaches.
Interested in comprehensive testing that includes optical genome mapping? View our test offerings or schedule a consultation with our team.
