GENOMICS
(SNVs), insertion-deletions (indels), and copy number variants (CNVs), further enhancing clinical utility.3
Streamlining with Devyser FH In 2021, following the discontinuation of the FH NGS assay in use, we validated an alternative amplicon-based NGS assay, Devyser FH v2, utilising a single- pool approach, significantly simplifying library preparation. This streamlined protocol substantially reduced hands-on time. Our validation criteria included comprehensive analytical performance metrics: sensitivity, specificity, accuracy, and quality control benchmarks (Q30 scores, minimum ≥50x coverage across all nucleotides within region of interest). Devyser FH v2 consistently met these stringent standards, demonstrating robust repeatability and reliability.4 Prior to validating the Devyser FH v2
kit, our laboratory also validated Devyser somatic BRCA kit for the detection of BRCA1 and BRCA2 variants in ovarian and prostate tumour samples. The samples were originally sequenced on the Illumina MiSeq. In order to further streamline the laboratory processes and reduce service costs, combined sequencing of Devyser FH v2 and BRCA somatic libraries was verified in July 2024. Combining 64-80 FH samples with up to 16 BRCA somatic samples on Illumina mid output NextSeq 550 flow cell and sequencing the libraries to a different read depth resulted in a five-fold reduction of the BRCA somatic sequencing cost while the FH sequencing cost remained unchanged.
Automation Another critical milestone was the automation of library preparation using Hamilton STARlet robotics. While initial runs yielded suboptimal read counts, iterative improvements through collaborative script adjustments between robotics and assay providers quickly resolved the issue. This collaborative approach underlines the importance of proactive cross-team engagement during automation. With all library preparation steps up to the pooling stage fully automated,
With added automation, hands-on time when preparing samples is cut significantly; reducing repetitive tasks and boosting staff satisfaction as well as confidence in reproducibility.
we observed significant operational improvements. The hands-on time required to prepare a batch of 64 samples has decreased significantly to approximately four hours, reducing repetitive tasks and boosting staff satisfaction and confidence in reproducibility.
Quality, costs, and operational gains Quality assurance evaluation across multiple runs demonstrated 100% concordance in the detection of known variants and consistently high coverage metrics, affirming the reliability of automated processes. These findings are consistent with the broader literature, which notes that automated NGS workflows significantly improve throughput and consistency while minimising error risk.5
sequencing costs by transitioning to larger sequencing batches, maintaining
cost equivalence, and improving resource utilisation. This could be further improved with the new Devyser Index Plate LB-192. Operational adjustments included an additional step to calculate sample loading concentrations by molarity using the Tapestation 4200, ensuring precise and optimal sequencing conditions and further enhancing workflow robustness and reliability. All analysis was performed by a third-party bioinformatics provider.
We also optimised
Clinical impact The impact of COVID-19 briefly affected our FH testing volumes, with reductions in clinical referrals due to the temporary closure of lipid clinics. However, post- pandemic volumes have stabilised, reflecting the resilience and adaptability of our service. This recovery also underscores the importance of building flexible diagnostic systems that can scale in response to public health disruptions. Genetic confirmation of FH enables
Studies have shown that integrating genetic confirmation in clinical pathways enhances cascade testing uptake and optimises treatment strategies
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WWW.PATHOLOGYINPRACTICE.COM September 2026
proactive family screening and early intervention, often starting in childhood. Using the updated referral criteria, we effectively link clinical guidelines with laboratory operations, emphasising patient-centred care and improved clinical outcomes through timely, accurate genetic diagnosis. Studies have shown that integrating genetic confirmation in clinical pathways enhances cascade testing uptake and optimises treatment strategies.2,6-7
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