Expected KL risk quantifies when first-order power-law approximations are sufficient

Biochemical Systems Theory (BST) often replaces nonlinear rate laws by first-order log-Taylor power-law approximations, but deciding when this truncation is adequate remains difficult. We derive a closed-form leading-order expression for the expected conditional Kullback-Leibler (KL) risk incurred by using the first-order model instead of the local second-order log expansion. Under Gaussian log-input fluctuations with covariance Σ and homoscedastic Gaussian log-output noise with variance [Formula: see text], the risk reduces to a trace contraction of the local log-curvature Hessian H with Σ. The criterion is therefore directly estimable from perturbation data or mechanistic models near an operating point. We also identify the leading correction from non-Gaussian inputs through fourth-order cumulants. Toy-model calculations and two biochemical case studies show that the criterion not only matches Monte Carlo estimates, but also identifies operating conditions and perturbation directions for which first-order BST is expected to fail.

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Publication Details

Journal
Scientific Reports
Published
2026-05-27
DOI
https://doi.org/10.1038/s41598-026-55101-y
Primary Topic
Gene Regulatory Network Analysis
Type
article
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article

Expected KL risk quantifies when first-order power-law approximations are sufficient

Chikoo Oosawa
Scientific Reports
Gene Regulatory Network Analysis
article

Expected KL risk quantifies when first-order power-law approximations are sufficient

Chikoo Oosawa
article en

Abstract

Biochemical Systems Theory (BST) often replaces nonlinear rate laws by first-order log-Taylor power-law approximations, but deciding when this truncation is adequate remains difficult. We derive a closed-form leading-order expression for the expected conditional Kullback-Leibler (KL) risk incurred by using the first-order model instead of the local second-order log expansion. Under Gaussian log-input fluctuations with covariance Σ and homoscedastic Gaussian log-output noise with variance [Formula: see text], the risk reduces to a trace contraction of the local log-curvature Hessian H with Σ. The criterion is therefore directly estimable from perturbation data or mechanistic models near an operating point. We also identify the leading correction from non-Gaussian inputs through fourth-order cumulants. Toy-model calculations and two biochemical case studies show that the criterion not only matches Monte Carlo estimates, but also identifies operating conditions and perturbation directions for which first-order BST is expected to fail.

Scientific Reports
Kyushu Institute of Technology (JP)
Peace, Justice and strong institutions
Openalex Percentile: Top 10%
Gene Regulatory Network Analysis
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