Periodic Report Summary 2 - PHYLOCANCER (Phylogeography and somatic evolution of cancer tumor cells)
The main goal of the PHYLOCANCER project is to understand tumor evolution in single patients using tools and concepts from evolutionary biology, exploiting single-cell whole genome data. During this time, most of our effort has been devoted to put together the set of laboratory and computational tools necessary for the production and analysis of single-cell genomes. Thus, we have focused on the assembly of the research group, obtention of tumor samples, establishment of a single-cell genomics laboratory, deployment of an appropriate computational structure for storing and processing massive amounts of genomic data, organization of NGS pipelines, and development of novel evolutionary models for single-cell data. During this period, our team has moved forward in multiple fronts, making advances in all the proposed tasks. We have built a brand-new single-cell genomics lab, where we have assessed multiple scWGA protocols and set up optimal sequencing and bioinformatic pipelines for processing single-cell genomes. We have started to apply these strategies to tumor samples from several colorectal cancer and chronic lymphocytic leukemia patients. During this time, we have also developed several statistical models for the simulation of tumor cell samples/populations that we are currently applying to understand the interactions of different evolutionary forces during tumor evolution, and to benchmark our bioinformatic pipelines. Finally, we have also implemented a novel and phylogenetic model for the analysis of single-cell genomes, able to estimate allelic dropout and the amplification/sequencing error rates. According to a preliminary benchmarking, this model outperforms the competing tools in terms of phylogenetic reconstruction.