607 research outputs found
Statistical inference of the mechanisms driving collective cell movement
Numerous biological processes, many impacting on human health, rely on collective cell
movement. We develop nine candidate models, based on advection-diffusion partial differential equations, to describe various alternative mechanisms that may drive cell movement. The parameters of these models were inferred from one-dimensional projections of laboratory observations of Dictyostelium discoideum cells by sampling from the posterior distribution using the delayed rejection adaptive Metropolis algorithm (DRAM). The best model was selected using the Widely Applicable Information Criterion (WAIC). We conclude that cell movement in our study system was driven both by a self-generated gradient in an attractant that the cells could deplete locally, and by chemical interactions between the cells
Learning action-oriented models through active inference
Converging theories suggest that organisms learn and exploit probabilistic models of their environment. However, it remains unclear how such models can be learned in practice. The open-ended complexity of natural environments means that it is generally infeasible for organisms to model their environment comprehensively. Alternatively, action-oriented models attempt to encode a parsimonious representation of adaptive agent-environment interactions. One approach to learning action-oriented models is to learn online in the presence of goal-directed behaviours. This constrains an agent to behaviourally relevant trajectories, reducing the diversity of the data a model need account for. Unfortunately, this approach can cause models to prematurely converge to sub-optimal solutions, through a process we refer to as a bad-bootstrap. Here, we exploit the normative framework of active inference to show that efficient action-oriented models can be learned by balancing goal-oriented and epistemic (information-seeking) behaviours in a principled manner. We illustrate our approach using a simple agent-based model of bacterial chemotaxis. We first demonstrate that learning via goal-directed behaviour indeed constrains models to behaviorally relevant aspects of the environment, but that this approach is prone to sub-optimal convergence. We then demonstrate that epistemic behaviours facilitate the construction of accurate and comprehensive models, but that these models are not tailored to any specific behavioural niche and are therefore less efficient in their use of data. Finally, we show that active inference agents learn models that are parsimonious, tailored to action, and which avoid bad bootstraps and sub-optimal convergence. Critically, our results indicate that models learned through active inference can support adaptive behaviour in spite of, and indeed because of, their departure from veridical representations of the environment. Our approach provides a principled method for learning adaptive models from limited interactions with an environment, highlighting a route to sample efficient learning algorithms
Identification of meat spoilage gene biomarkers in Pseudomonas putida using gene profiling
While current food science research mainly focuses on microbial changes in food products that lead to foodborne illnesses, meat spoilage remains as an unsolved problem for the meat industry. This can result in important economic losses, food waste and loss of consumer confidence in the meat market. Gram-negative bacteria involved in meat spoilage are aerobes or facultative anaerobes. These represent the group with the greatest meat spoilage potential, where Pseudomonas tend to dominate the microbial consortium under refrigeration and aerobic conditions. Identifying stress response genes under different environmental conditions can help researchers gain an understanding of how Pseudomonas adapts to current packaging and storage conditions. We examined the gene expression profile of Pseudomonas putida KT2440, which plays an important role in the spoilage of meat products. Gene expression profiles were evaluated to select the most differentially expressed genes at different temperatures (30 °C and 10 °C) and decreasing glucose concentrations, in order to identify key genes actively involved with the spoilage process. A total of 739 and 1269 were found to be differentially expressed at 30 °C and 10 °C respectively; of which 430 and 568 genes were overexpressed, and 309 and 701 genes were repressed at 30 °C and 10 °C respectively
Environmental statistics and optimal regulation
Any organism is embedded in an environment that changes over time. The
timescale for and statistics of environmental change, the precision with which
the organism can detect its environment, and the costs and benefits of
particular protein expression levels all will affect the suitability of
different strategies-such as constitutive expression or graded response-for
regulating protein levels in response to environmental inputs. We propose a
general framework-here specifically applied to the enzymatic regulation of
metabolism in response to changing concentrations of a basic nutrient-to
predict the optimal regulatory strategy given the statistics of fluctuations in
the environment and measurement apparatus, respectively, and the costs
associated with enzyme production. We use this framework to address three
fundamental questions: (i) when a cell should prefer thresholding to a graded
response; (ii) when there is a fitness advantage to implementing a Bayesian
decision rule; and (iii) when retaining memory of the past provides a selective
advantage. We specifically find that: (i) relative convexity of enzyme
expression cost and benefit influences the fitness of thresholding or graded
responses; (ii) intermediate levels of measurement uncertainty call for a
sophisticated Bayesian decision rule; and (iii) in dynamic contexts,
intermediate levels of uncertainty call for retaining memory of the past.
Statistical properties of the environment, such as variability and correlation
times, set optimal biochemical parameters, such as thresholds and decay rates
in signaling pathways. Our framework provides a theoretical basis for
interpreting molecular signal processing algorithms and a classification scheme
that organizes known regulatory strategies and may help conceptualize
heretofore unknown ones.Comment: 21 pages, 7 figure
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