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Register a new userEdge effects in game theoretic dynamics of spatially structured tumours
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Background: Analysing tumour architecture for metastatic potential usually focuses on phenotypic differences due to cellular morphology or specific genetic mutations, but often ignore the cells position within the heterogeneous substructure. Similar disregard for local neighborhood structure is common in mathematical models. Methods: We view the dynamics of disease progression as an evolutionary game between cellular phenotypes. A typical assumption in this modeling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard local heterogeneities. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go vs. grow game. Results: We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary -- such as a blood-vessel, organ capsule, or basement membrane -- we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (EMT positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Interpretation: Pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. We expect our approach to extend to other evolutionary game models where interaction neighborhoods change at fixed system boundaries.
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We review research papers which use game theory to model the decision making of individuals during an epidemic, attempting to classify the literature and identify the emerging trends in this field. We show that the literature can be classified based on (i) type of population modelling (compartmental or network-based), (ii) frequency of the game (non-iterative or iterative), and (iii) type of strategy adoption (self-evaluation or imitation). We highlight that the choice of model depends on many factors such as the type of immunity the disease confers, the type of immunity the vaccine confers, and size of population and level of mixing therein. We show that while early studies used compartmental modelling with self-evaluation based strategy adoption, the recent trend is to use network-based modelling with imitation-based strategy adoption. Our review indicates that game theory continues to be an effective tool to model intervention (vaccination or social distancing) decision-making by individuals.
The spreading dynamics of an epidemic and the collective behavioral pattern of the population over which it spreads are deeply intertwined and the latter can critically shape the outcome of the former. Motivated by this, we design a parsimonious game-theoretic behavioral--epidemic model, in which an interplay of realistic factors shapes the co-evolution of individual decision-making and epidemics on a network. Although such a co-evolution is deeply intertwined in the real-world, existing models schematize population behavior as instantaneously reactive, thus being unable to capture human behavior in the long term. Our model offers a unified framework to model and predict complex emergent phenomena, including successful collective responses, periodic oscillations, and resurgent epidemic outbreaks. The framework also allows to assess the effectiveness of different policy interventions on ensuring a collective response that successfully eradicates the outbreak. Two case studies, inspired by real-world diseases, are presented to illustrate the potentialities of the proposed model.
Evolutionary game dynamics is one of the most fruitful frameworks for studying evolution in different disciplines, from Biology to Economics. Within this context, the approach of choice for many researchers is the so-called replicator equation, that describes mathematically the idea that those individuals performing better have more offspring and thus their frequency in the population grows. While very many interesting results have been obtained with this equation in the three decades elapsed since it was first proposed, it is important to realize the limits of its applicability. One particularly relevant issue in this respect is that of non-mean-field effects, that may arise from temporal fluctuations or from spatial correlations, both neglected in the replicator equation. This review discusses these temporal and spatial effects focusing on the non-trivial modifications they induce when compared to the outcome of replicator dynamics. Alongside this question, the hypothesis of linearity and its relation to the choice of the rule for strategy update is also analyzed. The discussion is presented in terms of the emergence of cooperation, as one of the current key problems in Biology and in other disciplines.
In evolutionary processes, population structure has a substantial effect on natural selection. Here, we analyze how motion of individuals affects constant selection in structured populations. Motion is relevant because it leads to changes in the distribution of types as mutations march toward fixation or extinction. We describe motion as the swapping of individuals on graphs, and more generally as the shuffling of individuals between reproductive updates. Beginning with a one-dimensional graph, the cycle, we prove that motion suppresses natural selection for death-birth updating or for any process that combines birth-death and death-birth updating. If the rule is purely birth-death updating, no change in fixation probability appears in the presence of motion. We further investigate how motion affects evolution on the square lattice and weighted graphs. In the case of weighted graphs we find that motion can be either an amplifier or a suppressor of natural selection. In some cases, whether it is one or the other can be a function of the relative reproductive rate, indicating that motion is a subtle and complex attribute of evolving populations. As a first step towards understanding less restricted types of motion in evolutionary graph theory, we consider a similar rule on dynamic graphs induced by a spatial flow and find qualitatively similar results indicating that continuous motion also suppresses natural selection.
Tumour cells have to acquire a number of capabilities if a neoplasm is to become a cancer. One of these key capabilities is increased motility which is needed for invasion of other tissues and metastasis. This paper presents a qualitative mathematical model based on game theory and computer simulations using cellular automata. With this model we study the circumstances under which mutations that confer increased motility to cells can spread through a tumour made of rapidly proliferating cells. The analysis suggests therapies that could help prevent the progression towards malignancy and invasiveness of benign tumours.
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