Developing modified Lotka-Volterra models to simulate in vitro clonal dynamics

Abstract

During the last decades, novel technological approaches have allowed uniquely labelling cells by integrating random barcodes in their DNAs. Such barcodes are permanent and are inherited by the cellular offspring. Thus, DNA sequencing permits their reading in order to identify those cells with common ancestors. This process, known as lineage tracing, enables the study of complex biological processes such as embryonic development, tissue homeostasis or even cancer metastasis with clonal, and even single cell, resolution. Here we aim to reveal the foundations behind the experimental results of clonal dynamics of colon cancer organoids through in silico simulations. We formulated three modified Lotka-Volterra models that allow us to investigate the role of clonal carrying capacity, proliferation rates and inter-clonal interaction network to achieve our purpose. The results show the vital role of partial interactions among clones and the importance of implementing nonequilibrium networks, i.e. architectures of interactions that vary in time. Furthermore, our results reveal a direct relationship between the harvesting time and the average number of surviving species at the end of the experiment, suggesting that external perturbations to the system can have big effects to clonal dynamics