Inferring Cancer Progression from Single-cell Sequencing while Allowing Mutation Losses

Abstract

AbstractMotivationIn recent years, the well-known Infinite Sites Assumption (ISA) has been a fundamental feature of computational methods devised for reconstructing tumor phylogenies and inferring cancer progressions seen as an accumulation of mutations. However, recent studies (Kuiperset al., 2017) leveraging Single-cell Sequencing (SCS) techniques have shown evidence of the widespread recurrence and, especially, loss of mutations in several tumor samples. Still, established methods that can infer phylogenies with mutation losses are however lacking.ResultsWe present theSASC(Simulated Annealing Single-Cell inference) tool which is a new and robust approach based on simulated annealing for the inference of cancer progression from SCS data. More precisely, we introduce a simple extension of the model of evolution where mutations are only accumulated, by allowing also a limited amount of back mutations in the evolutionary history of the tumor: the Dollo-kmodel. We demonstrate thatSASCachieves high levels of accuracy when tested on both simulated and real data sets and in comparison with some other available methods.AvailabilityThe Simulated Annealing Single-cell inference (SASC) tool is open source and available athttps://github.com/sciccolella/sasc.Contacts.ciccolella@campus.unimib.it