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Matt Thomson

Publications and source records attributed to Matt Thomson.

38 records · Page 3Linked to original sources

Physically optimizing inference

Data is scaling exponentially in fields ranging from genomics to neuroscience to economics. A central question is: can modern machine learning methods be applied to construct predictive models of natural systems like cells and brains based on large data sets? In this paper, we examine how inference is impacted when training data is generated by the statistical behavior of a physical system, and hence outside direct control by the experimentalist. We develop an information-theoretic analysis for the canonical problem of spin-network inference. Our analysis reveals the essential role that the physical properties of the spin network and its environment play in determining the difficulty of the underlying machine learning problem. Specifically, stochastic fluctuations drive a system to explore a range of configurations providing `raw' information for a learning algorithm to construct an accurate model; yet they also blur energetic differences between network states and thereby degrade information. This competition leads spin networks to generically have an intrinsic optimal temperature at which stochastic spin fluctuations provide maximal information for discriminating among competing models, maximizing inference efficiency. We demonstrate a simple active learning protocol that optimizes network temperature to boost inference efficiency and dramatically increases the efficiency of inference on a neural circuit reconstruction task. Our results reveal a fundamental link between physics and information and show how the physical environment can be tuned to optimize the efficiency of machine learning.

cond-mat.stat-mech↗

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.

q-bio.QM↗