Bayes-Optimal Chemotaxis

Mortimer, Duncan; Dayan, Peter; Burrage, Kevin; Goodhill, Geoffrey J.

doi:10.1162/neco_a_00075

Cited by 21 publications

(20 citation statements)

References 56 publications

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“…[This is similar to the observation that a small difference of two large numbers always has a larger relative error than either of the two numbers, and so one is frequently cautioned against making such subtractions in scientific computing (43).] This decrease has been observed in many systems (12,13,22,(44)(45)(46)(47) and typically attributed to receptor saturation, whereas our analysis suggests that it is present even for linear systems. Indeed, high-affinity EGF receptors (K D ≈ 300 pM) generally constitute ∼ 10% of the total receptor pool, and low-affinity receptors (K D ≈ 2 nM) constitute the remaining ∼ 90% (48).…”

Section: Resultscontrasting

confidence: 42%

Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Ellison

Mugler

Brennan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

135

108

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Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and little is known about how multicellular signal processing modulates single-cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored whether cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow epidermal growth factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells. gradient sensing | development | collective cellular phenomena | linear response theory | chemotaxis

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Section: Resultscontrasting

confidence: 42%

Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Ellison

Mugler

Brennan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

135

108

View full text Add to dashboard Cite

show abstract

“…The previous works we built on (Mortimer et al, 2009(Mortimer et al, , 2011Hu et al, 2011aHu et al, , 2011bBaba et al, 2012) derived the posterior distribution of the gradient by assuming a uniform distribution of receptors on the sensing device, and a large enough number of receptors such that the Gaussian approximation holds for the magnitude and the direction of the gradient. In contrast, we use the mutual information instead of Fisher information, which makes our approach more suitable to analyse the case of a finite or small number of receptors (thousands or fewer).…”

Section: Discussionmentioning

confidence: 99%

“…A powerful approach for analysing such problems is to consider the optimal statistical inference that an ideal observer would perform (Andrews and Iglesias, 2007;Mortimer et al, 2009;Fuller et al, 2010;Hu et al, 2010Hu et al, , 2011aMortimer et al, 2011). This involves combining available information with prior assumptions.…”

Section: Introductionmentioning

confidence: 99%

The influence of receptor positioning on chemotactic information

Nguyen

Dayan

Goodhill

2014

Journal of Theoretical Biology

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“…The previous works we built on [95,[97][98][99]230] derived the posterior distribution of the gradient by assuming a uniform distribution of receptors on the sensing device, and a large enough number of receptors such that the Gaussian approximation holds for the magnitude and the direction of the gradient. In contrast, we use the mutual information instead of Fisher information, which makes our approach more suitable to analyse the case of a finite or small number of receptors (thousands or fewer).…”

Section: Discussionmentioning

confidence: 99%

Mathematical modelling of axon guidance in chemical gradients

Nguyen¹

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Correct wiring is crucial to the proper functioning of the nervous system. Key signals guiding growth cones, the motile tips of developing axons, to their targets are molecular gradients. The receptors on the membrane of the growth cone bind stochastically with guidance molecules in the environment, giving an estimate of the direction of the gradient. The growth cone then executes biased random movements to navigate toward the chemoattractant source or away from the chemorepellent source. This thesis addresses two questions: 1) how the positioning and diffusion of receptors on the growth cone membrane affect the accuracy of gradient estimation, 2) how trajectories are influenced by chemical gradients.Membrane receptors can diffuse freely on the membrane, smearing out the directional information about the gradient. It was unknown how the positioning and diffusion of receptors affect the estimate of the gradient. To address question (1) above, we utilise an ideal-observer approach, assuming that the growth cone can perform maximum likelihood estimation of the gradient based on the stochastic binding patterns with ligand molecules. The performance of gradient sensing is measured by the Fisher Information between the binding pattern and the gradient direction. The quality of gradient sensing decreases with higher diffusion constant of the receptors and improves with higher concentration. We then extend to a two-dimensional model of an elliptical growth cone with a general prior distribution. With a random uniform distribution of receptors, the shape of the growth cone can introduce bias in the gradient estimate. This bias can be corrected by a non-uniform distribution of receptors with higher density near the minor axis of the growth cone.Besides stochastic gradient sensing, growth cones also trace highly stochastic trajectories, and it is unclear how molecular gradients bias their movement. We then introduce a mathematical model of a correlated random walk based on persistence, bias and noise to describe growth cone trajectories, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model explains the long-standing mystery that average axon turning angles in gradients in vitro plateau very rapidly with time at relatively small values of 10-20• . This work introduces the most accurate predictive model of growth cone trajectories to date, and calls into question the ability of molecular gradients alone to provide reliable guidance cues for growing axons.ii Declaration by AuthorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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Bayes-Optimal Chemotaxis

Cited by 21 publications

References 56 publications

Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

The influence of receptor positioning on chemotactic information

Mathematical modelling of axon guidance in chemical gradients

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