Multi-omics study reveals psychiatric comorbidities in bladder pain syndrome patients while demonstrating advantages in hematological malignancies and repeat expansion analysis.
Nabsys 2.0 LLC presented data at the American Society of Human Genetics Annual Meeting demonstrating novel disease insights and applications of its OhmX Platform across multiple disease states, including interstitial cystitis/bladder pain syndrome (IC/BPS), hematological malignancies, and repeat expansion disorders.
The most notable findings came from a multi-disciplinary team at Boston Children’s Hospital, which conducted a multi-omics study of IC/BPS combining exome sequencing with the Nabsys OhmX Platform analysis. The study analyzed 248 individuals from the Boston Children’s Hospital IC/BPS cohort and compared results against 100 individuals from the Maryland Genetics of Interstitial Cystitis Study cohort, totaling 348 participants compared to 11,981 controls.
Key findings revealed that 70% of individuals with IC/BPS had a psychiatric diagnosis, with the majority being depressive and anxiety disorders (55%). Proteomics data showed 13 differentially expressed proteins and enrichment of several pathways. While no single gene was associated with risk for IC/BPS, collapsing analyses identified new candidates including DYX1C1 and HTR7, alongside a significant association with the “small molecule transport” gene pathway.
“Interstitial cystitis and bladder pain syndrome are characterized by persistent and distressing symptoms that frequently lead to poor quality of life and high levels of mental stress, but there is no known cause or available treatment option for this condition, which affects millions of people in the US alone,” says Elicia A Estrella, MS, LCGC, Boston Children’s Hospital, in a release.
Structural Variant Detection Capabilities
The study strengthened associations between IC/BPS and previously identified Mendelian disease genes (ATP2C1, DCAF8, SIX5, ENAM, and ATP2A2) with an odds ratio of 7.4. Notably, researchers utilized the Nabsys OhmX Platform to identify a previously undetected translocation (t3;9) involving NOTCH1 in one individual.
Nabsys also presented three additional posters highlighting the OhmX Platform’s capabilities in electronic genome mapping (EGM). The platform successfully mapped a reciprocal PML::RARA gene fusion event, a BCR::ABL1 translocation, and several TP53 deletions using dense, sequence-specific tagging and electronic detection with approximately 300 bp resolution. These structural variants are clinically significant in hematologic malignancies.
For repeat expansion disorders, researchers developed a new pipeline called RepX Analysis for Repeat Disorders, finding that EGM represents an improvement over existing repeat expansion analysis tools for conditions like Fragile X syndrome, the most common inherited form of intellectual disability.
CRISPR Integration Enhances Platform Performance
The research team also demonstrated how CRISPR/Cas9 technology integration can enhance the EGM workflow by repairing double-stranded breaks caused by sample preparation and increasing specific tagging density to improve genome mapping resolution.
“Looking specifically at Nabsys’s work detecting translocations and TP53 deletions, we found that our proprietary EGM methodology identified these markers of hematologic cancers with incredible accuracy, demonstrating the value of this platform as a scalable and cost-effective solution in translational cancer research,” says Barrett Bready, MD, founder and CEO of Nabsys, in a release.
The company presented eight EGM presentations total at the ASHG meeting, with presentation materials available on the company’s website resources section.
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