Speaker: Sahand Hormoz, Harvard Medical School, Dana-Farber Cancer Institute

Title: Insights from single cell lineage trees

Abstract: In this talk, I will discuss two recent projects from my lab that involve lineage trees of cells (the branching diagram that represents the ancestry and division history of individual cells). In the first project, we reconstructed the lineage trees of individual cancer cells from the patterns of randomly occurring mutations in these cells. We then inferred the age at which the cancer mutation first occurred and the rate of expansion of the population of cancer cells within each patient. To our surprise, we discovered that the cancer mutation occurs decades before diagnosis. For the second project, we developed microfluidic ‘mother machines’ that allow us to observe mammalian cells dividing across tens of generations. Using our observations, we calculated the correlation between the duration of cell cycle phases in pairs of cells, as a function of their lineage distance. These correlations revealed many surprises that we are trying to understand using hidden Markov models on trees. For both projects, I will discuss the mathematical challenges that we have faced and open problems related to inference from lineage trees.