At ASHG 2025, Rebecca Barnard, PhD (Twist Bioscience), presented new data demonstrating how a PCR-free, hybrid-capture sequencing workflow—developed through collaboration between Twist Bioscience and Element Biosciences—enables accurate detection of disease-causing short tandem repeat (STR) expansions. These repetitive sequences, known to underlie disorders such as Huntington’s disease, Fragile X syndrome, and myotonic dystrophy, have historically been difficult to resolve due to amplification bias, GC-rich regions, and somatic mosaicism. The combined Twist Enzymatic Fragmentation library prep with full-length adapters and Element’s Avidity Base Chemistry eliminates on-instrument PCR, improving coverage of complex, GC-dense loci and maintaining the original repeat structure. Barnard’s results showed clear detection of both normal and pathogenic alleles—including expanded DMPK genotypes (22/84 repeats)—while reducing hands-on time by up to five hours per workflow. The presentation highlights how this Trinity PCR-free solution advances repeat-expansion analysis with greater accuracy, speed, and scalability for research applications.