Written by Charlotte Harrison, Science Writer
Liquid biopsy assays that detect circulating tumour (ct) DNA are safer and faster than traditional solid tumour approaches, and also offer the potential to assess the heterogeneity of the malignant process. To better understand the potential clinical validity and utility of ctDNA assays, a consortium of researchers has released a comprehensive dataset from a liquid biopsy proficiency study.
Assessing ctDNA assays
The consortium — known as the Sequencing Quality Control Phase II Oncopanel Sequencing Working Group — developed a novel study design to assess the analytical performance of ctDNA assays. The study design used tailor-made DNA samples that had multiple DNA input levels and sequencing depths, 12 testing laboratories and ctDNA assays from five companies including Burning Rock Biotech, Integrated DNA Technologies, Illumina, Roche Sequencing Solutions, and Thermo Fisher Scientific.
Data published last year in a research paper showed that there is currently insufficient evidence of clinical validity and utility for the majority of cancer-based liquid biopsy assays. This finding is especially true concerning early-stage diagnosis, treatment monitoring and residual disease monitoring.
A data set for further analyses
The newly available dataset encompasses multiple key variables, including a broad range of mutation frequencies, sequencing coverage depth, DNA input quantity, and so on. The authors note that it is the most comprehensive public-facing dataset of its kind and provides valuable insights into ultra-deep ctDNA sequencing technology.
The authors advocate that the dataset can be used for further analyses to elicit additional insights. Specifically, it can be mined for a better understanding of the ctDNA technology, including:
1) Making the best use of unique molecular identifiers for error correction
2) Better understanding the impact of sequence context / genomic regions on low-frequency variant calling
3) Improving the accuracy of small-indel calling
4) Improving the accuracy of variant calling with spike-in controls
5) Developing bioinformatics pipelines or tuning the parameters of pipelines to improve the sensitivity and reproducibility for low-frequency variants
Overall, the research paper and the accompanying dataset provide important steps towards the clinical use of liquid biopsy assays.
Image Credit: Canva