Parameter-wise predictions and sensitivity analysis for random walk models in the life sciences

Sensitivity analysis characterises input-output relationships for mathematical models, and has been widely applied to deterministic models across many applications in the life sciences. In contrast, sensitivity analysis for stochastic models has received less attention, with most previous work focusing on well-mixed, non-spatial problems. For explicit spatio-temporal stochastic models, such as random walk models (RWMs), sensitivity analysis has received far less attention. Here we present a new type of sensitivity analysis, called parameter-wise prediction, for two types of biologically-motivated and computationally expensive RWMs. To overcome the limitations of directly analysing stochastic simulations, we employ continuum-limit partial differential equation (PDE) descriptions as surrogate models, and we link these efficient surrogate descriptions to the RWMs using a range of biophysically-motivated measurement error models. Our approach is likelihood-based, which means that we also consider likelihood-based parameter estimation and identifiability analysis along with parameter sensitivity. The new approach is presented for two important classes of lattice-based RWM including a classical model where crowding effects are neglected, and an exclusion process model that explicitly incorporates crowding. Our workflow illustrates how different process models can be combined with different measurement error models to reveal how each parameter impacts the outcome of the expensive stochastic simulation. Open-access software to replicate all results is available on GitHub (Liu, 2025).

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Publication Details

Journal
Journal of Theoretical Biology
Published
2025-12-27
DOI
https://doi.org/10.1016/j.jtbi.2025.112347
Primary Topic
Gene Regulatory Network Analysis
Type
article
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article

Parameter-wise predictions and sensitivity analysis for random walk models in the life sciences

Matthew J. Simpson, Yihan Liu, David J. Warne
Journal of Theoretical Biology
Gene Regulatory Network Analysis
article

Parameter-wise predictions and sensitivity analysis for random walk models in the life sciences

Matthew J. Simpson, Yihan Liu, David J. Warne
article en

Abstract

Sensitivity analysis characterises input-output relationships for mathematical models, and has been widely applied to deterministic models across many applications in the life sciences. In contrast, sensitivity analysis for stochastic models has received less attention, with most previous work focusing on well-mixed, non-spatial problems. For explicit spatio-temporal stochastic models, such as random walk models (RWMs), sensitivity analysis has received far less attention. Here we present a new type of sensitivity analysis, called parameter-wise prediction, for two types of biologically-motivated and computationally expensive RWMs. To overcome the limitations of directly analysing stochastic simulations, we employ continuum-limit partial differential equation (PDE) descriptions as surrogate models, and we link these efficient surrogate descriptions to the RWMs using a range of biophysically-motivated measurement error models. Our approach is likelihood-based, which means that we also consider likelihood-based parameter estimation and identifiability analysis along with parameter sensitivity. The new approach is presented for two important classes of lattice-based RWM including a classical model where crowding effects are neglected, and an exclusion process model that explicitly incorporates crowding. Our workflow illustrates how different process models can be combined with different measurement error models to reveal how each parameter impacts the outcome of the expensive stochastic simulation. Open-access software to replicate all results is available on GitHub (Liu, 2025).

Journal of Theoretical BiologyVol. 621
Queensland University of Technology (AU)
Openalex Percentile: Top 36%
Gene Regulatory Network Analysis
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Parameter-wise predictions and sensitivity analysis for random walk models in the life sciences — Matthew J. Simpson, Yihan Liu, et al. · Journal of Theoretical Biology (2025) | TGRS Research Map | TGRS