报告主题：Elucidating Intratumor Heterogeneity from Single-cell DNA Sequencing Data
报告摘要：Intra-tumor heterogeneity, as caused by a combination of mutation and selection, poses significant challenges to the diagnosis and clinical therapy of cancer. Resolving this heterogeneity to identify the tumor cell populations (clones) and delineate their evolutionary history is of critical importance in improving cancer diagnosis and therapy. This heterogeneity can be readily elucidated and understood through the reconstruction of the clonal genotypes and evolutionary history of the tumor cells. These tasks are challenging since genomic data is most often collected from one snapshot during the evolution of the tumor's constituent cells. Consequently, using computational methods that infer the tumor phylogeny and tumor subpopulations from sequence data is the approach of choice. Recently emerged single-cell DNA sequencing (SCS) technologies promise to resolve intra-tumor heterogeneity to a single-cell level. However, inherent technical errors in SCS datasets, including false-positive (FP) errors, false-negatives (FN) due to allelic dropout, cell doublets and coverage non-uniformity significantly complicate these tasks.
In this talk, I will first describe a maximum likelihood method for inferring tumor trees from imperfect SCS genotype data with potentially missing entries, under a finite-sites model of evolution. I will then describe a non-parametric Bayesian method that simultaneously reconstructs the clonal populations as clusters of single cells, mutations associated with each clone, and the genealogical relationships between the clonal populations. I will demonstrate the performance of the methods on both synthetic and real data sets.