ECLIPSE (subclone tracking from ctDNA)

ECLIPSE is the bioinformatic tool the TRACERx team built to call the presence or absence of individual tumour subclones in plasma and estimate their cancer cell fractions from low-tumour-content cell-free DNA (Abbosh et al., Nature 2023). It uses a background error estimate for each sample and copy number from multi-region tumour sequencing, and was applied to anchored multiplex PCR panels tracking a median of 200 mutations per patient, with up to 4 mL of plasma per case.

Its stated operating point is the most useful single number on how far subclone attribution reaches: plasma with a clonal ctDNA level of 0.1 per cent (1,000 parts per million) had an estimated minimally detectable cancer cell fraction of 20 per cent for a representative subclone, and simulated subclones built from the assay's dilution validation data gave 94 per cent detection sensitivity for a 20 per cent subclone at that level with four tracked mutations and 10 ng of DNA. Detection fell below 10 ng, so only samples with at least 0.1 per cent clonal ctDNA and 10 ng input were analysed for clonal composition. ECLIPSE found patients with polyclonal metastatic dissemination, which carried a worse outcome, and subclones that later seeded metastases were more expanded in preoperative plasma.