Simulation-based Methods for Optimal Sampling Design in Systems Biology

TL;DR

This paper introduces two novel simulation-based methods for optimal sampling in systems biology that do not require initial parameter estimates, improving accuracy over classical methods.

Contribution

It presents EOR and LSTM-based methods for sampling design, overcoming limitations of traditional Fisher information matrix approaches.

Findings

Proposed methods outperform classical E-optimal design.

Simulation studies validate effectiveness on biological models.

Methods do not depend on initial parameter estimates.

Abstract

In many areas of systems biology, including virology, pharmacokinetics, and population biology, dynamical systems are commonly used to describe biological processes. These systems can be characterized by estimating their parameters from sampled data. The key problem is how to optimally select sampling points to achieve accurate parameter estimation. Classical approaches often rely on Fisher information matrix-based criteria such as A-, D-, and E-optimality, which require an initial parameter estimate and may yield suboptimal results when the estimate is inaccurate. This study proposes two simulation-based methods for optimal sampling design that do not depend on initial parameter estimates. The first method, E-optimal-ranking (EOR), employs the E-optimal criterion, while the second utilizes a Long Short-Term Memory (LSTM) neural network. Simulation studies based on the Lotka-Volterra and three-compartment models demonstrate that the proposed methods outperform both random selection and classical E-optimal design.