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McDonald, T. O.

Publications and source records attributed to McDonald, T. O..

2 recordsLinked to original sources

evosim: fast and scalable stochastic simulations of evolutionary dynamics

The simulation of clonal dynamics with branching processes can provide valuable insights into disease progression and treatment optimization, but exact simulation of branching processes via the Stochastic Simulation Algorithm (SSA) is computationally prohibitive at the large population sizes associated with therapeutically-relevant scenarios. evosim is a versatile and flexible Python implementation of a fast and unbiased tau-leaping algorithm for the simulation of birth-death-mutation branching processes that is scalable to any population size. Package functionalities support the incorporation and tracking of a sequence of evolutionary changes such as therapeutic interventions as well as the analysis of population diversity. We show that runtimes scale logarithmically with population size, by contrast to the linear scaling of the SSA, and simulations exhibit strong agreement with SSA simulation results. These findings are also supported by mathematical results (Supplementary information). AvailabilityPackage, documentation, and tutorials / usage examples are available on GitHub (https://github.com/daliten/evosim). Mathematical details of the algorithm and the pseudocode are provided in the included Supplementary information.

evolutionary biology↗

Single-cell genetic heterogeneity linked to immune infiltration in glioblastoma.

Glioblastoma (GBM) is the most aggressive brain tumor with a median survival of ~15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. To uncover the relationships between genetically diverse subpopulations of GBM cells and their native tumor microenvironment, we employed highly multiplexed spatial protein profiling, coupled with single-cell spatial mapping of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA. Single-cell FISH analysis of a total of 35,843 single nuclei (~2,100 per tumor) revealed that tumors in which amplifications of EGFR and CDK4 more frequently co-occur in the same cell exhibit higher infiltration of CD163+ immunosuppressive macrophages. Our results suggest that high throughput assessment of genomic alterations at the single cell level could provide a measure for predicting the immune state of GBM.

cancer biology↗