Multiplexed Somatic Cancer Assays

AGBT 2023, Hollywood, FL

Assessment of the Utility of a Novel Massively Parallel Sequencing Platform for Multiplexed Somatic Cancer Assays.

Sophie Low1, Michelle Cipicchio1, Daniel Stover2, Nicole Francis1, Ning Li1, Mark Fleharty1, Micah Rickles-Young1, Carrie Cibulskis1, Stacey Gabriel1, Niall Lennon1
Broad Institute of MIT and Harvard, 320 Charles St, Cambridge, MA 02141
2Ohio State University Cancer Center, Columbus, OH 43210

Tumor profiling using next generation sequencing can provide powerful information to guide patient diagnosis and care, however enabling flexibility in scale can be a challenge for core labs. Cancer specific panels are an important tool for both research and clinical testing. Projects vary significantly in scope, with variable sample numbers, target territory and sequencing depth required. Expanding into high sensitivity platforms using unique molecular index error correction requires low sequencing cost per base due to the very deep coverage required. Cancer research requires flexible scale, with throughput that may be too low to leverage the most cost-effective sequencing options available. Despite substantial multiplexing capabilities, high-throughput sequencers do not often fit well with smaller scale clinical testing platforms that require fast turn-around times and the ability to process a few samples at a time. We are exploring a novel sequencing platform that can provide a solution to enable flexibility in scale while matching the most advantageous cost. With high quality, low error NGS reads of up to 150 bp, the Element AVITI benchtop sequencer provides a solution with flexible scale that would enable small batch sizes.

We present an analysis of a Pan Cancer gene profiling panel using deep sequencing on samples with somatic variants at known allele fractions. Additionally, we assess the performance of ultra-low coverage whole genome sequencing for tumor fraction estimation from liquid biopsy. We will evaluate this platform for workflow, cost effectiveness, and variant calling sensitivity and specificity. The low error rate on this platform, combined with the attractive per base cost and flexible scale, represents a solution for the complex challenges limiting the use of NGS in cancer today.

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