Seminar Summary

The EDIT Summer Seminars continued with a talk by Nathaniel V. Mon Père, PhD. Dr. Mon Père is a postdoctoral researcher at the Barts Cancer Institute, Queen Mary University of London. His research focuses on the mathematical study of somatic evolution and genetic heterogeneity in healthy and cancerous tissues. He uses methods from population genetics, dynamical systems, stochastic processes, and numerical analysis, with a particular focus on stochastic differential equations and spatial stochastic models.

During this edition of the EDIT SumS, Dr. Mon Père presented his recently published paper in Cancer Discovery (see below). The study investigates clonal hematopoiesis, a process in which hematopoietic stem cells acquire selectively advantageous mutations and expand within the blood-producing cell population as individuals age. The authors developed a model of polyclonal competition in which advantageous clones continually emerge and compete within the hematopoietic stem-cell population. By combining stochastic differential equations with agent-based modeling, they estimated both the distribution of clone fitness and the rate at which advantageous clonal expansions occur. These quantities were inferred independently from longitudinal variant trajectories and sample site frequency spectra, with both approaches producing consistent results. Their results show how competition among expanding clones can restrict the number of clones that become detectable, even when advantageous mutations occur repeatedly. The study also identified evidence of multistep evolution across several well-known clonal hematopoiesis driver genes. DNMT3A variants were enriched among single-hit clones, whereas TET2, ASXL1, JAK2, SF3B1, and SRSF2 showed stronger evidence of multistep evolutionary processes. The fittest clones also tended to emerge later in life, consistent with the progressive accumulation of advantageous alterations. Dr. Mon Père’s talk demonstrated how stochastic and agent-based models can connect individual clone trajectories with population-level patterns of clonal hematopoiesis. These findings help explain previously unresolved features of blood evolution and suggest that evolutionary precursors of hematologic malignancies may be identifiable before malignant transformation, potentially creating opportunities for earlier monitoring and intervention.

Resources

Dr. Mon Père’s profile: Barts Cancer Institute

The paper presented: The Evolution of Polyclonal Competition in Aging Hematopoiesis