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Identifying high-confidence mutations in plasma

xGen® Dual Index UMI Adapters–Tech Access enable detection of low-frequency variants

Confident signal detection and variant calling pose a significant challenge to researchers sequencing circulating tumor DNA (ctDNA). Learn how AstraZeneca investigators use the unique molecular indexes (UMIs) within xGen Dual Index UMI Adapters–Tech Access to confidently identify low-frequency variants in ctDNA samples.

Sequencing of circulating tumor DNA (ctDNA) obtained from liquid biopsies provides a comprehensive, up-to-date snapshot of a patient’s disease state. It can also detect rare variants or changes in tumor mutation profiles.

However, a liquid biopsy contains a very limited quantity of ctDNA, and is contaminated by genomic DNA, exosomes, and even circulating cell-free RNA. Confidently calling low-frequency—but potentially important—variants in the face of those additional signal-to-noise challenges therefore requires extremely stringent and highly sensitive methods. The unique molecular identifier (UMI) sequences present in IDT xGen Dual Index UMI Adapters–Tech Access enable detection of such low-frequency variants and aid with de-duplicating reads during post-sequence analysis.

In this webinar, Dr Iwanka Kozarewa and Daniel Stetson, from the Translational Science Genomics group within the AstraZeneca Innovative Medicines and Early Development (IMED) Biotech Unit, share examples of how they use xGen Dual Index UMI Adapters–Tech Access to improve the sensitivity of their ctDNA sequencing. By using dual index UMI adapters in conjunction with multiple longitudinal samples, they have been able to confidently identify mutations present at allele frequencies as low as 0.17 to 2%. Kozarewa and Stetson also discuss how UMIs have enabled them to aggressively pursue the development of a machine learning approach for variant calling. Finally, the scientists discuss their dual UMI duplex sequencing strategy for greater noise suppression that pushes sensitivity even further.

For additional information on xGen Dual Index UMI Adapters–Tech Access, or to place custom orders, please contact our scientific applications support group .

Published Sep 3, 2020