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In this review we summarize our recent efforts in trying to understand the role of heterogeneity in cancer progression by using neural networks to characterise different aspects of the mapping from a cancer cells genotype and environment to its phenotype. Our central premise is that cancer is an evolving system subject to mutation and selection, and the primary conduit for these processes to occur is the cancer cell whose behaviour is regulated on multiple biological scales. The selection pressure is mainly driven by the microenvironment that the tumour is growing in and this acts directly upon the cell phenotype. In turn, the phenotype is driven by the intracellular pathways that are regulated by the genotype. Integrating all of these processes is a massive undertaking and requires bridging many biological scales (i.e. genotype, pathway, phenotype and environment) that we will only scratch the surface of in this review. We will focus on models that use neural networks as a means of connecting these different biological scales, since they allow us to easily create heterogeneity for selection to act upon and importantly this heterogeneity can be implemented at different biological scales. More specifically, we consider three different neural networks that bridge different aspects of these scales and the dialogue with the micro-environment, (i) the impact of the micro-environment on evolutionary dynamics, (ii) the mapping from genotype to phenotype under drug-induced perturbations and (iii) pathway activity in both normal and cancer cells under different micro-environmental conditions.
A small but growing number of people are finding interesting parallels between ecosystems as studied by ecologists (think of a Savanna or the Amazon rain forest or a Coral reef) and tumours1-3. The idea of viewing cancer from an ecological perspectiv
A principal component analysis of the TCGA data for 15 cancer localizations unveils the following qualitative facts about tumors: 1) The state of a tissue in gene expression space may be described by a few variables. In particular, there is a single
Understanding cell-fate decisions during tumorigenesis and metastasis is a major challenge in modern cancer biology. One canonical cell-fate decision that cancer cells undergo is Epithelial-to-Mesenchymal Transition (EMT) and its reverse Mesenchymal-
Cancer cells maintain a high level of aerobic glycolysis (the Warburg effect), which is associated with their rapid proliferation. Many studies have reported that the suppression of glycolysis and activation of oxidative phosphorylation can repress t
Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species