{"title":"Evolving Improved Sampling Protocols for Dose-Response Modelling Using Genetic Algorithms with a Profile-Likelihood Metric.","authors":"Nicholas N Lam, Rua Murray, Paul D Docherty","doi":"10.1007/s11538-024-01304-1","DOIUrl":null,"url":null,"abstract":"<p><p>Practical limitations of quality and quantity of data can limit the precision of parameter identification in mathematical models. Model-based experimental design approaches have been developed to minimise parameter uncertainty, but the majority of these approaches have relied on first-order approximations of model sensitivity at a local point in parameter space. Practical identifiability approaches such as profile-likelihood have shown potential for quantifying parameter uncertainty beyond linear approximations. This research presents a genetic algorithm approach to optimise sample timing across various parameterisations of a demonstrative PK-PD model with the goal of aiding experimental design. The optimisation relies on a chosen metric of parameter uncertainty that is based on the profile-likelihood method. Additionally, the approach considers cases where multiple parameter scenarios may require simultaneous optimisation. The genetic algorithm approach was able to locate near-optimal sampling protocols for a wide range of sample number (n = 3-20), and it reduced the parameter variance metric by 33-37% on average. The profile-likelihood metric also correlated well with an existing Monte Carlo-based metric (with a worst-case r > 0.89), while reducing computational cost by an order of magnitude. The combination of the new profile-likelihood metric and the genetic algorithm demonstrate the feasibility of considering the nonlinear nature of models in optimal experimental design at a reasonable computational cost. The outputs of such a process could allow for experimenters to either improve parameter certainty given a fixed number of samples, or reduce sample quantity while retaining the same level of parameter certainty.</p>","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"86 6","pages":"70"},"PeriodicalIF":2.0000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078857/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bulletin of Mathematical Biology","FirstCategoryId":"100","ListUrlMain":"https://doi.org/10.1007/s11538-024-01304-1","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Practical limitations of quality and quantity of data can limit the precision of parameter identification in mathematical models. Model-based experimental design approaches have been developed to minimise parameter uncertainty, but the majority of these approaches have relied on first-order approximations of model sensitivity at a local point in parameter space. Practical identifiability approaches such as profile-likelihood have shown potential for quantifying parameter uncertainty beyond linear approximations. This research presents a genetic algorithm approach to optimise sample timing across various parameterisations of a demonstrative PK-PD model with the goal of aiding experimental design. The optimisation relies on a chosen metric of parameter uncertainty that is based on the profile-likelihood method. Additionally, the approach considers cases where multiple parameter scenarios may require simultaneous optimisation. The genetic algorithm approach was able to locate near-optimal sampling protocols for a wide range of sample number (n = 3-20), and it reduced the parameter variance metric by 33-37% on average. The profile-likelihood metric also correlated well with an existing Monte Carlo-based metric (with a worst-case r > 0.89), while reducing computational cost by an order of magnitude. The combination of the new profile-likelihood metric and the genetic algorithm demonstrate the feasibility of considering the nonlinear nature of models in optimal experimental design at a reasonable computational cost. The outputs of such a process could allow for experimenters to either improve parameter certainty given a fixed number of samples, or reduce sample quantity while retaining the same level of parameter certainty.
期刊介绍:
The Bulletin of Mathematical Biology, the official journal of the Society for Mathematical Biology, disseminates original research findings and other information relevant to the interface of biology and the mathematical sciences. Contributions should have relevance to both fields. In order to accommodate the broad scope of new developments, the journal accepts a variety of contributions, including:
Original research articles focused on new biological insights gained with the help of tools from the mathematical sciences or new mathematical tools and methods with demonstrated applicability to biological investigations
Research in mathematical biology education
Reviews
Commentaries
Perspectives, and contributions that discuss issues important to the profession
All contributions are peer-reviewed.