NuProbe Technology Enables Accurate Quantitation of Mutations Below 0.01% VAF using Low-Depth Sequencing

HOUSTON, Oct. 21, 2021 /PRNewswire/ -- NuProbe scientists and collaborators recently announced research demonstrating the accurate quantitation of somatic mutations below 0.01% variant allele frequency (VAF). By integrating molecular barcoding technology with the Blocker Displacement Amplification (BDA) allele enrichment, the team invented the new quantitative BDA (QBDA) method that overcomes potential biases in BDA to enable accurate VAF quantitation. The findings, published in Nature Communications, are the latest research developed by NuProbe for molecular detection of minimal residual disease (MRD) for cancer applications.

"Sequencing DNA variants with low allelic frequency has important clinical and biological implications, but, with current NGS technologies, the required high assay sensitivity leads to sequencing depths unaffordable for many researchers, clinicians, and patients - limiting access to this critical data," noted Peng Dai, PhD, coauthor of the study and Senior Scientist at NuProbe. 

QBDA integrates sequence-selective variant enrichment into UMI quantitation for accurate determination of mutations below 0.01% VAF, allowing a sensitive MRD detection. When applied to clinical patient samples during complete remission, QBDA detected residual mutation at 0.0052% VAF while the MRD was missed by both multicolor flow cytometry and conventional NGS. The specific mutation was further confirmed by conventional NGS at relapse, indicating QBDA's accuracy of rare mutation detection and the potential of early detection.

"In diseases like acute myeloid leukemia (AML), the sensitive detection of MRD could impact the prognosis for patients in remission by identifying a submicroscopic disease," said Dr. Ghayas Issa, a medical oncologist at The University of Texas MD Anderson Cancer Center and coauthor of the study. "This study indicates QBDA has potential to increase early detection, guiding treatment decisions sooner." 

Testing of the QBDA technology was completed on a 20-gene AML panel, a 61-gene pan-cancer panel, and a melanoma hotspot panel covering 8-genes. In addition to mutation calls at less than 0.01% VAF, the study highlights QBDA's ability to use low input DNA (<20 ng) with as low as 3,000X sequencing depth to detect mutations above 0.1% VAF using NuProbe's VarMap Pan-Cancer and Melanoma Panels in various sample types including tissue DNA and cfDNA.

"Accurate quantitation of mutation VAFs are critical for longitudinal monitoring patients for minimum residual disease. Our QBDA technology combines the affordability of BDA allele enrichment with the quantitative accuracy of unique molecular identifier barcoding. We envision that QBDA will be a powerful method for enabling frequent, accurate, and noninvasive molecular testing of cancer patients to provide timely information on adjusting potential treatment," said David Zhang, Co-founder and General Manager at NuProbe USA and corresponding author of the study. "NuProbe is committed to developing technologies that can lead to improvements in oncology diagnostics, treatments, and research."

NuProbe's VarMap Pan-Cancer and Melanoma panels are for Research Use Only and are not intended for In Vitro Diagnostic use. 

About NuProbe Global
NuProbe is a cutting-edge genomics and molecular diagnostics company with revolutionary molecular diagnostic technologies to improve the sensitivity of sequencing mutations and copy number variations by over 10-fold. NuProbe has sites in Houston, USA, Shanghai, China and Suzhou, China. NuProbe's vision is to offer affordable, timely, and accurate disease state information to enable precision medicine and improve patient outcomes.

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