Quantitative systems pharmacology and machine learning: a match made in heaven or hell?

Tindall, M. J. ORCID: https://orcid.org/0000-0001-6069-5260, Cucurull-Sanchez, L., Mistry, H. and Yates, J. W.T. (2023) Quantitative systems pharmacology and machine learning: a match made in heaven or hell? The Journal of Pharmacology and Experimental Therapeutics, 387 (1). pp. 92-99. ISSN 1521-0103 doi: 10.1124/jpet.122.001551

Abstract/Summary

As pharmaceutical development moves from early stage in vitro experimentation to later in vivo and subsequent clinical trials, data and knowledge are acquired across multiple time and length scales, from the subcellular to whole patient cohort scale. Realising the potential of this data for informing decision making in pharmaceutical development requires the individual and combined application of machine learning (ML) and mechanistic multiscale mathematical modelling approaches. Here we outline how these two approaches, both individually and in tandem, can be applied at different stages of the drug discovery and development pipeline to inform decision making compound development. The importance of discerning between knowledge and data is highlighted in informing the initial use of ML or mechanistic Quantitative Systems Pharmacology (QSP) models. We discuss the application of sensitivity and structural identifiability analyses of QSP models in informing future experimental studies, to which ML may be applied, as well as how ML approaches can be used to inform mechanistic model development. Relevant literature studies are highlighted and we close by discussing caveats regarding the application of each approach in an age of constant data acquisition. We consider when best to apply Machine Learning (ML) and mechanistic Quantitative Systems Pharmacology (QSP) approaches in the context of the drug discovery and development pipeline. We discuss the importance of prior knowledge and data available for the system of interest and how this informs the individual and combined application of ML and QSP approaches at each stage of the pipeline.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/113319
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Science > School of Mathematical, Physical and Computational Sciences > Department of Mathematics and Statistics
Uncontrolled Keywords	Mathematical modeling, drug development/discovery
Publisher	American Society for Pharmacology and Experimental Therapeutics
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