Limits on the computational expressivity of non-equilibrium biophysical processes

Abstract 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 severa...

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Main Authors: Carlos Floyd, Aaron R. Dinner, Arvind Murugan, Suriyanarayanan Vaikuntanathan
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61873-0
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author Carlos Floyd
Aaron R. Dinner
Arvind Murugan
Suriyanarayanan Vaikuntanathan
author_facet Carlos Floyd
Aaron R. Dinner
Arvind Murugan
Suriyanarayanan Vaikuntanathan
author_sort Carlos Floyd
collection DOAJ
description Abstract 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.
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issn 2041-1723
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publishDate 2025-08-01
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series Nature Communications
spelling doaj-art-df6c8efca1a4415f81b7e0b230bd63ac2025-08-20T03:43:14ZengNature PortfolioNature Communications2041-17232025-08-0116111210.1038/s41467-025-61873-0Limits on the computational expressivity of non-equilibrium biophysical processesCarlos Floyd0Aaron R. Dinner1Arvind Murugan2Suriyanarayanan Vaikuntanathan3The Chicago Center for Theoretical Chemistry, The University of ChicagoThe Chicago Center for Theoretical Chemistry, The University of ChicagoThe James Franck Institute, The University of ChicagoThe Chicago Center for Theoretical Chemistry, The University of ChicagoAbstract 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.https://doi.org/10.1038/s41467-025-61873-0
spellingShingle Carlos Floyd
Aaron R. Dinner
Arvind Murugan
Suriyanarayanan Vaikuntanathan
Limits on the computational expressivity of non-equilibrium biophysical processes
Nature Communications
title Limits on the computational expressivity of non-equilibrium biophysical processes
title_full Limits on the computational expressivity of non-equilibrium biophysical processes
title_fullStr Limits on the computational expressivity of non-equilibrium biophysical processes
title_full_unstemmed Limits on the computational expressivity of non-equilibrium biophysical processes
title_short Limits on the computational expressivity of non-equilibrium biophysical processes
title_sort limits on the computational expressivity of non equilibrium biophysical processes
url https://doi.org/10.1038/s41467-025-61873-0
work_keys_str_mv AT carlosfloyd limitsonthecomputationalexpressivityofnonequilibriumbiophysicalprocesses
AT aaronrdinner limitsonthecomputationalexpressivityofnonequilibriumbiophysicalprocesses
AT arvindmurugan limitsonthecomputationalexpressivityofnonequilibriumbiophysicalprocesses
AT suriyanarayananvaikuntanathan limitsonthecomputationalexpressivityofnonequilibriumbiophysicalprocesses