Quest Diagnostics with Covaris launches automated NGS platform, optimizing workflows to maximize lab economics
In a recent webinar, Ryan Serra, PhD, Sr. Director of Molecular Genomics and Oncology and Genomic Sequencing Services at Quest Diagnostics, Matthew Gallen, MPH, Scientific Director of R&D at Quest Diagnostics, and Sameer Vasantgadkar, Sr. Manager, Omics at Covaris, discussed their collaborative effort in developing an industry–leading, highly automated next-generation sequencing platform. This cutting-edge system optimizes workflows to maximize lab economics.
With advancements in next-generation sequencing (NGS), the genomics industry is on the cusp of a major transformation, offering a favorable opportunity for those who have the capacity to scale. Currently, gene panels serve as the primary method for testing, but with the anticipated reduction in sequencing costs, a shift towards whole genome sequencing is expected. Precise control over high throughput processes will be a prerequisite for success in this growing testing segment.
One of the critical steps in NGS is the controlled processing of DNA fragments. Covaris’ Adaptive Focused Acoustics® (AFA®) technology delivers precise isothermal mechanical shearing of nucleic acids, resulting in unbiased fragmentation and high recovery. Quest Diagnostics collaborated with Covaris to integrate AFA technology with the Covaris R230 Focused-ultrasonicator into Quest’s Genomic Sequencing Services NGS platform. The goal was to create a new, fully integrated, scalable, high-throughput NGS platform. This integration enabled automation across multiple NGS assays, leading to a more uniform process and improved sequencing QC metrics.
By integrating the R230 into their automation, Quest addressed scalability and compatibility issues they had previously encountered with enzymatic fragmentation, such as added complexity and increased failure rates. Now fully automated with the R230, the process allows for high-quality, reproducible assays, offering cost savings and more robust workflows while minimizing errors from complex reactions.
Results from Sizing Studies Show Drastically Improved Workflow Performance
The effectiveness of this approach is evident in the data obtained from the development and production of the Genetic Insights assay. As seen in Figure 1, in hybrid capture NGS workflows, the fragmentation upfront directly correlates with the enrichment after hybridization. The data reveals that mechanical fragmentation results in a threefold increase in fold enrichments upon sequencing compared to enzymatic fragmentation (represented in orange).
This suggests that workflows benefit from a more stable commencement point, drastically increasing performance downstream. It also increases targeting and makes for more uniform batches, which improves multi-flexibility through workflows and on sequencers. Ultimately, this results in lower assay failure rates and decreases the turnaround time for delivering results to patients. From both a testing performance and an economics perspective, these improvements have a substantial impact, boosting the overall efficiency of these workflows.
Figure 1. More uniform DNA shearing leads to better enrichment.
Figure 2 shows the distribution for enzymatic fragmentation (represented by yellow/green portion) has a noticeably wider distribution compared to Covaris mechanical fragmentation (depicted in blue). For paired-end sequencing, Covaris’ consistent insert sizes mean that overlaps between forward and reverse reads are predictable. This reduces the cost for extra sequencing depth to ensure adequate coverage, as overlapping reads can be merged or properly aligned.
Figure 2. Distribution for enzymatic fragmentation and mechanical fragmentation
Another key finding, as depicted in Figure 3, is the consistency of Covaris fragmentation across different specimen types, including whole blood, saliva, and prenatal samples for cultured amnios. The data shows that there can be multiple input specimen types incorporated into workflows without introducing the significant variability and kit changes seen in enzymatic fragmentation reactions. This consistency enhances the robustness of the approach when dealing with multiple inputs, diverse patient populations, and clinical utilities. It also strengthens workflows right from the beginning, which impacts downstream sequencing reactions.
Figure 3. Consistency of Covaris fragmentation across various sample types is shown.
Utilizing Covaris AFA Technology for More Efficient Workflows
Covaris’ AFA technology provides high value solutions in the pre-analytical sample prep domain. It facilitates efficient extraction and processing of biomolecules from a wide range of sample types, ensuring robustness and reproducibility. By using a high frequency, non-contact ultrasonication method, AFA technology delivers acoustic energy in a concentrated manner, eliminating the potential of contamination.
What’s more, the high-quality data output from the AFA process offers deeper insights into areas such as oncology, biomarker detection, drug screening, and pathway analysis. These insights lead to actionable data that can improve and save lives.
AFA technology is versatile, compatible with various sample types, and serves as a universal shearing platform for NGS, protein, or -omic workflows. It provides a streamlined workflow with standardized protocols, making it especially useful when handling diverse input sample concentrations.
Figure 4. AFA technology demonstrates better targeting, more uniform batches and lower assay failure rates.
AFA technology is not only scalable but also compatible with automation, effectively addressing both current and future high-throughput processing needs. This positions it as the gold standard for initiating NGS.
Quest Diagnostics’ efforts to refine their NGS processes have been greatly aided by Covaris’ innovative AFA technology. This partnership has resulted in significant progress in genetic testing. It holds the promise of delivering more robust, scalable, and cost-effective solutions, setting a new standard in the industry and taking steps toward improving patient outcomes and optimizing healthcare.
Eager to learn more about the Covaris R230 Focused-ultrasonicator or how to improve efficiencies by incorporating AFA technology into your workflow? Click here to contact one of our specialists.