Development of SARS-CoV-2 NGS Internal Standards to Ensure Sufficient Complexity Capture for Variant Detection and Diagnosis

This project aims to Implement SNAQ-SEQ IS in COVID-19 testing to improve our nation’s response to detecting new COVID-19 variants, lead to better COVID-19 diagnosis and treatment monitoring, and support a support better response to future viral outbreaks

Industry Need

Next-Generation Sequencing (NGS) is a well-established diagnostic method widely used in oncology, the study of genetic disorders, and increasingly in diagnosing infectious diseases.
NGS is prone to many errors that negatively affect assay performance without causing detectable failure including variability with reagents and instruments.
How much (or how little) of the sample information (complexity) captured in sequence data, especially when viral load is low, is often overlooked in NGS testing of SARS-CoV-2.
To address these errors, necessary and sufficient quality control measures should be built into each reaction of the NGS assay.

Approach

AccuGenomics has developed Internal Standards (IS) for Standardized Nucleic Acid Quantification for Sequencing (SNAQ-SEQ) that provide a direct and precise quantification of SARS-CoV-2 sequence present in each sample. The IS acts as a positive control, comprised of a known set and quantity of RNA molecules that biochemically mimic the behavior of the SARS-CoV-2 genome present in each sample.

The IS, when added, indicates if every sample achieves sufficient analytic sensitivity and specificity. Comparing the expected amount of IS product to the actual measured IS response allows for the genetic variability in the sample to be accurately quantifiable. AccuGenomics IS diagnostic testing standardizes the amount of information required for a sample to yield a valid result and allows for comparison across assays.

Impacts

Created a shelf stable SNAQ SARS-CoV-2 Internal Standard material

Demonstrated Standardized Nucleic Acid Quantification (SNAQ) analysis benefits in an interlaboratory study, specifically analysis of viral load, sensitivity, and specificity

Help improve the nation's response to detecting new SARS-CoV-2 variants by ensuring quality surveillance data, leading to better COVID-19 diagnosis and treatment monitoring, and supporting more accurate and reliable development testing of future viral outbreaks

Value Statement/Outcomes

By integrating Internal Standards (IS) for Standardized Nucleic Acid Quantification for Sequencing (SNAQ-SEQ) Internal Standards into NGS workflows, laboratories can eliminate "silent failures" and reagent variability, potentially reducing expensive diagnostic re-run rates by 20–30%. The use of biochemically mimetic RNA controls enables precise quantification of low viral loads, increasing analytical sensitivity and ensuring that 100% of samples meet standardized "information yield" thresholds for clinical validity. Furthermore, the transition to a lyophilized format enhances reagent stability, extending shelf life and reducing QC-related logistics costs by providing a robust, cross-platform benchmark for genomic complexity.

Outputs/Deliverables

Improve the stability of the SNAQ SARS-CoV-2 Internal Standard material Demonstrate the analytical utility of the lyophilized SARS-CoV-2 internal standard

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Project Lead

Accugenomics Inc