Quantifying the seed sensitivity of cancer subclonal reconstruction algorithms

Intra-tumoural heterogeneity complicates cancer prognosis and impairs treatment success. One of the ways subclonal reconstruction (SRC) quantifies intra-tumoural heterogeneity is by estimating the number of subclones present in bulk DNA sequencing data. SRC algorithms are probabilistic and need to be initialized by a random seed. However, the seeds used in bioinformatics algorithms are rarely reported in the literature. Thus, the impact of the initializing seed on SRC solutions has not been studied. To address this gap, we generated a set of ten random seeds to systematically benchmark the seed sensitivity of three probabilistic SRC algorithms: PyClone-VI, DPClust, and PhyloWGS.