Inferring fungal growth rates from optical density data

PLoS Comput Biol. 2024 May 16;20(5):e1012105. doi: 10.1371/journal.pcbi.1012105. eCollection 2024 May.

Abstract

Quantifying fungal growth underpins our ability to effectively treat severe fungal infections. Current methods quantify fungal growth rates from time-course morphology-specific data, such as hyphal length data. However, automated large-scale collection of such data lies beyond the scope of most clinical microbiology laboratories. In this paper, we propose a mathematical model of fungal growth to estimate morphology-specific growth rates from easy-to-collect, but indirect, optical density (OD600) data of Aspergillus fumigatus growth (filamentous fungus). Our method accounts for OD600 being an indirect measure by explicitly including the relationship between the indirect OD600 measurements and the calibrating true fungal growth in the model. Therefore, the method does not require de novo generation of calibration data. Our model outperformed reference models at fitting to and predicting OD600 growth curves and overcame observed discrepancies between morphology-specific rates inferred from OD600 versus directly measured data in reference models that did not include calibration.

MeSH terms

  • Aspergillus fumigatus* / growth & development
  • Computational Biology / methods
  • Models, Biological*

Grants and funding

This research was funded in whole, or in part, by the Wellcome Trust [Grant number 215358/Z/19/Z to T.H.], https://wellcome.org/. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This project was partly funded by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Studentship (NC/P00217X/1), https://nc3rs.org.uk/. E.B acknowledges support from the MRC Centre for Medical Mycology at the University of Exeter (MR/N006364/2 and MR/V033417/1). Work in the laboratory of E.B. was funded by MRC project grants MR/M02010X/1, MR/S001824/1, and MR/L000822/1 and by a Biotechnology and Biological Sciences Research Council (BBSRC) project grant BB/V017004/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.