Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

4 Sep 2017  ·  Daniele Ramazzotti, Alex Graudenzi, Luca De Sano, Marco Antoniotti, Giulio Caravagna ·

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data... Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses. read more

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