title: Modelling evolutionary cell behaviour using neural networks: application to tumour growth.
abstract: In this paper, we present a modelling framework for cellular evolution that is based on the notion that a cell's behaviour is driven by interactions with other cells and its immediate environment. We equip each cell with a phenotype that determines its behaviour and implement a decision mechanism to allow evolution of this phenotype. This decision mechanism is modelled using feed-forward neural networks, which have been suggested as suitable models of cell signalling pathways. The environmental variables are presented as inputs to the network and result in a response that corresponds to the phenotype of the cell. The response of the network is determined by the network parameters, which are subject to mutations when the cells divide. This approach is versatile as there are no restrictions on what the input or output nodes represent, they can be chosen to represent any environmental variables and behaviours that are of importance to the cell population under consideration. This framework was implemented in an individual-based model of solid tumour growth in order to investigate the impact of the tissue oxygen concentration on the growth and evolutionary dynamics of the tumour. Our results show that the oxygen concentration affects the tumour at the morphological level, but more importantly has a direct impact on the evolutionary dynamics. When the supply of oxygen is limited we observe a faster divergence away from the initial genotype, a higher population diversity and faster evolution towards aggressive phenotypes. The implementation of this framework suggests that this approach is well suited for modelling systems where evolution plays an important role and where a changing environment exerts selection pressure on the evolving population.
authors.affiliation: Niels Bohr Institute, Center for Models of Life, Blegdamsvej 17, 2100 Copenhagen, Denmark. gerlee@nbi.dk
authors.forename: P
authors.initials: P
authors.lastname: Gerlee
authors.forename: A R A
authors.initials: AR
authors.lastname: Anderson
mesh_terms: D005075:Biological Evolution; D049109:Cell Proliferation; D003198:Computer Simulation; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D016571:Neural Networks, Computer; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology
chemical_list: D010100:Oxygen