Published August 5, 2025 | Version v1
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Limits on the computational expressivity of non-equilibrium biophysical processes

Description

Many biological decision-making tasks require classifying high-dimensional chemical states. The biophysical and computational mechanisms that enable classification remain enigmatic. In this work, using Markov jump processes as an abstraction of general biochemical networks, we reveal several unanticipated and universal limitations on the classification ability of generic biophysical processes. These limits arise from a fundamental non-equilibrium thermodynamic constraint that we have derived. Importantly, we show that these limitations can be overcome using common biochemical mechanisms that we term input multiplicity, examples of which include enzymes acting on multiple targets. Analogous to how increasing depth enhances the expressivity and classification ability of neural networks, our work demonstrates how tuning input multiplicity can potentially enable an exponential increase in a biological system's ability to classify and process information.

Data availability

No datasets were generated in this study. Mathematica code used to generate the results in the manuscript is available at https://github.com/csfloyd/NonEqExpressivity.

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Additional details

Identifiers

DOI
10.1038/s41467-025-61873-0
Other
oai:uchicago.tind.io:16003

Funding

National Institute of General Medical Sciences
R35GM147400
National Institute of General Medical Sciences
R35GM151211
National Science Foundation
PHY-2317138
University of Chicago
Chicago Center for Theoretical Chemistry Fellowship

UChicago Information

Division(s)
Physical Sciences Division
Department(s)
Chemistry, Physics
Center(s) or Institute(s)
Chicago Center for Theoretical Chemistry, James Franck Institute