Bridge Capture Permits Cost-Efficient, Rapid and Sensitive Molecular Precision Diagnostics

Abstract

AbstractLiquid biopsies are gaining popularity as a less invasive alternative to tissue biopsies that have been the mainstay of cancer diagnostics to date. Recently, the quantification of mutations in circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) has been gaining popularity. Targeted NGS approaches are preferable in ctDNA analysis as they provide greater sequencing depth and affordability compared to whole genome NGS. Targeted NGS can be achieved through various library preparation methods, each with distinct advantages and limitations. Here we introduce Bridge Capture, a novel technology that combines the advantages of market-leading liquid biopsy technologies while eliminating the need to compromise between scalability, cost-efficiency, sensitivity, or panel size. We compared Bridge Capture to leading commercial technologies currently available in cancer diagnostics; Archer™ LIQUIDPlex™ and AmpliSeq™ Cancer HotSpot Panel v2 for Illumina®. We found high mutant allele frequency (MAF) concordance as well as the lowest MAF among the three technologies on matched contrived colorectal biospecimens mimicking ctDNA. We showed the reproducibility of Bridge Capture by observing a high correlation between results from two independent laboratories. Additionally, we demonstrate the capability of Bridge Capture to affordably utilize bench-top sequencers for low MAF patient samples. Therefore, we believe that Bridge Capture will considerably enhance cancer diagnostics as a cost efficient, simple, rapid and sensitive precision diagnostic tool.