Single-cell sequencing enables the inference of tumor phylogenies that provide insights on intra-tumor heterogeneity and evolutionary trajectories. Recently introduced methods perform this task under the infinite-sites assumption, violations of which, due to chromosomal deletions and loss of heterozygosity, necessitate the development of inference methods that utilize finite-sites models. We propose a statistical inference method for tumor phylogenies from noisy single-cell sequencing data under a finite-sites model. The performance of our method on synthetic and experimental data sets from two colorectal cancer patients to trace evolutionary lineages in primary and metastatic tumors suggests that employing a finite-sites model leads to improved inference of tumor phylogenies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1311-2) contains supplementary material, which is available to authorized users.

Single-cell sequencing (SCS) enables the inference of tumor phylogenies that provide insights on intra-tumor heterogeneity and evolutionary trajectories. Recently introduced methods perform this task under the infinite-sites assumption, violations of which, due to chromosomal deletions and loss of heterozygosity, necessitate the development of inference methods that utilize finite-site models. We propose a statistical inference method for tumor phylogenies from noisy SCS data under a finite-sites model. The performance of our method on synthetic and experimental datasets from two colorectal cancer patients to trace evolutionary lineages in primary and metastatic tumors suggest that employing a finite-sites model leads to improved inference of tumor phylogenies.

Q(i, j) denotes transition from state i to state j. The transitions for which the entry is 'NA', are not allowed. In particular, we do not allow the transitions 0/-→ 1/-or 1/-→0/as a reflection of a simplifying assumption that a recurrent point mutation and deletion/LOH occurring at the same site is a very rare event. Furthermore, we do not model copy number gain.