Convergence, sampling and total order estimator effects on parameter orthogonality in global sensitivity analysis

SAXTON, Harry, XU, Xu, SCHENKEL, Torsten, CLAYTON, Richard H. and HALLIDAY, Ian (2024). Convergence, sampling and total order estimator effects on parameter orthogonality in global sensitivity analysis. [Pre-print] (Unpublished)

Preprints have not been peer-reviewed. They should not be relied on to guide clinical practice or health related behaviour and should not be regarded as conclusive or be reported in news media as established information.
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Official URL: http://dx.doi.org/10.1101/2024.02.25.582013
Open Access URL: https://www.biorxiv.org/content/10.1101/2024.02.25... (Submitted version)

Abstract

Dynamical system models typically involve numerous input parameters whose “effects” and orthogonality need to be quantified through sensitivity analysis, to identify inputs contributing the greatest uncertainty. Whilst prior art has compared total-order estimators’ role in recovering “true” effects, assessing their ability to recover robust parameter orthogonality for use in identifiability metrics has not been investigated. In this paper, we perform: (i) an assessment using a different class of numerical models representing the cardiovascular system, (ii) a wider evaluation of sampling methodologies and their interactions with estimators, (iii) an investigation of the consequences of permuting estimators and sampling methodologies on input parameter orthogonality, (iv) a study of sample convergence through resampling, and (v) an assessment of whether positive outcomes are sustained when model input dimensionality increases. Our results indicate that Jansen or Janon estimators display efficient convergence with minimum uncertainty when coupled with Sobol and the lattice rule sampling methods, making them prime choices for calculating parameter orthogonality and influence. This study reveals that global sensitivity analysis is convergence driven. Unconverged indices are subject to error and therefore the true influence or orthogonality of the input parameters are not recovered. This investigation importantly clarifies the interactions of the estimator and the sampling methodology by reducing the associated ambiguities, defining novel practices for modelling in the life sciences.

Item Type: Pre-print
Identification Number: https://doi.org/10.1101/2024.02.25.582013
SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 19 Mar 2024 11:06
Last Modified: 19 Mar 2024 11:06
URI: https://shura.shu.ac.uk/id/eprint/33442

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