Uncertainty quantification in mechanistic epidemic models via cross-entropy approximate Bayesian computation.

This paper proposes a data-driven approximate Bayesian computation framework for parameter estimation and uncertainty quantification of epidemic models, which incorporates two novelties: (i) the identification of the initial conditions by using plausible dynamic states that are compatible with observational data; (ii) learning of an informative prior distribution for the model parameters via the cross-entropy method. The new methodology's effectiveness is illustrated with the aid of actual data from the COVID-19 epidemic in Rio de Janeiro city in Brazil, employing an ordinary differential equation-based model with a generalized SEIR mechanistic structure that includes time-dependent transmission rate, asymptomatics, and hospitalizations. A minimization problem with two cost terms (number of hospitalizations and deaths) is formulated, and twelve parameters are identified. The calibrated model provides a consistent description of the available data, able to extrapolate forecasts over a few weeks, making the proposed methodology very appealing for real-time epidemic modeling.

Data-driven modelling of social forces and collective behaviour in zebrafish.

Zebrafish are rapidly emerging as a powerful model organism in hypothesis-driven studies targeting a number of functional and dysfunctional processes. Mathematical models of zebrafish behaviour can inform the design of experiments, through the unprecedented ability to perform pilot trials on a computer. At the same time, in-silico experiments could help refining the analysis of real data, by enabling the systematic investigation of key neurobehavioural factors. Here, we establish a data-driven model of zebrafish social interaction. Specifically, we derive a set of interaction rules to capture the primary response mechanisms which have been observed experimentally. Contrary to previous studies, we include dynamic speed regulation in addition to turning responses, which together provide attractive, repulsive and alignment interactions between individuals. The resulting multi-agent model provides a novel, bottom-up framework to describe both the spontaneous motion and individual-level interaction dynamics of zebrafish, inferred directly from experimental observations.

Data-driven stochastic modelling of zebrafish locomotion.

In this work, we develop a data-driven modelling framework to reproduce the locomotion of fish in a confined environment. Specifically, we highlight the primary characteristics of the motion of individual zebrafish (Danio rerio), and study how these can be suitably encapsulated within a mathematical framework utilising a limited number of calibrated model parameters. Using data captured from individual zebrafish via automated visual tracking, we develop a model using stochastic differential equations and describe fish as a self propelled particle moving in a plane. Based on recent experimental evidence of the importance of speed regulation in social behaviour, we extend stochastic models of fish locomotion by introducing experimentally-derived processes describing dynamic speed regulation. Salient metrics are defined which are then used to calibrate key parameters of coupled stochastic differential equations, describing both speed and angular speed of swimming fish. The effects of external constraints are also included, based on experimentally observed responses. Understanding the spontaneous dynamics of zebrafish using a bottom-up, purely data-driven approach is expected to yield a modelling framework for quantitative investigation of individual behaviour in the presence of various external constraints or biological assays.

Analytical modelling of the spread of disease in confined and crowded spaces.

Since 1927 and until recently, most models describing the spread of disease have been of compartmental type, based on the assumption that populations are homogeneous and well-mixed. Recent models have utilised agent-based models and complex networks to explicitly study heterogeneous interaction patterns, but this leads to an increasing computational complexity. Compartmental models are appealing because of their simplicity, but their parameters, especially the transmission rate, are complex and depend on a number of factors, which makes it hard to predict how a change of a single environmental, demographic, or epidemiological factor will affect the population. Therefore, in this contribution we propose a middle ground, utilising crowd-behaviour research to improve compartmental models in crowded situations. We show how both the rate of infection as well as the walking speed depend on the local crowd density around an infected individual. The combined effect is that the rate of infection at a population scale has an analytically tractable non-linear dependency on crowd density. We model the spread of a hypothetical disease in a corridor and compare our new model with a typical compartmental model, which highlights the regime in which current models may not produce credible results.

How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch.

Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-engineering and Modelling Assessment (IRMA). Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics.