DICE: fast and accurate distance-based reconstruction of single-cell copy number phylogenies.

Abstract

Somatic copy number alterations (sCNAs) are valuable phylogenetic markers for inferring evolutionary relationships among tumor cell subpopulations. Advances in single-cell DNA sequencing technologies are making it possible to obtain such sCNAs datasets at ever-larger scales. However, existing methods for reconstructing phylogenies from sCNAs are often too slow for large datasets. We propose two new distance-based methods, DICE-bar and DICE-star, for reconstructing single-cell tumor phylogenies from sCNA data. Using carefully simulated datasets, we find that DICE-bar matches or exceeds the accuracies of all other methods on noise-free datasets and that DICE-star shows exceptional robustness to noise and outperforms all other methods on noisy datasets. Both methods are also orders of magnitude faster than many existing methods. Our experimental analysis also reveals how noise/error in copy number inference, as expected for real datasets, can drastically impact the accuracies of most methods. We apply DICE-star, the most accurate method on error-prone datasets, to several real single-cell breast and ovarian cancer datasets and find that it rapidly produces phylogenies of equivalent or greater reliability compared with existing methods.