Mathematical modelling of interacting sub-populations in glioblastoma

MathOnc
MathOnco
Bioinformatics
Pseudotime
GBM
Cancer
Authors
Affiliations

Nicholas Harbour

Center for Mathematical Medicine and Biology, University of Nottingham, UK

Lee Curtin

Mathematical Neuro-Oncology Lab, Mayo Clinci, AZ, USA

Michael Chappell

Precision Imaging Center, Universtiy of Nottingham, UK

Matthew Hubbard

School of Mathematical Sciences, University of Nottingham, UK

Kristin Swanson

Mathematical Neuro-Oncology Lab, Mayo Clinci, AZ, USA

Markus Owen

Center for Mathematical Medicine and Biology, University of Nottingham, UK

Published

May 1, 2023

Abstract

One of the major challenges in successfully treating glioblastoma (GBM) is the significant heterogeneity in cellular composition observed within and between patients. Recent single cell transcriptomics suggests there can be as many as eighteen distinct cell types in a single tumour (Al-Dalahmah et al. 2021). Furthermore, advances in cellular deconvolution techniques, such as CIBERSORTx, allow us to accurately determine the cellular composition of imaged localised biopsies from bulk RNA-Seq (Steen et al. 2020) . Understanding this heterogeneity and how the complex interactions between cellular populations impacts the progression of GBM may lead to novel treatments which exploit the unique cellular composition within individual tumours. We group these eighteen cell types into sub-populations, e.g., glioma, immune, astrocyte, then attempt to learn the dynamics of these sub-populations by considering various interacting ODE/PDE models. Typically, a GBM patient will have biopsies taken at most twice, as well as only a handful of MRI scans. Therefore, the number of temporal data points to fit any model to are very limited. Thus, we apply trajectory inference methods, such as Monocle, to biopsy data, which allows us to order samples via pseudotime, an arbitrary unit of progress akin to real time (Trapnell et al. 2014). We illustrate our modelling approach with a simplified two species Lotka-Volterra style competition model.

Poster

References

Al-Dalahmah, Osama, Michael G. Argenziano, Adithya Kannan, Aayushi Mahajan, Julia Furnari, Fahad Paryani, Deborah Boyett, et al. 2021. “Re-Convolving the Compositional Landscape of Primary and Recurrent Glioblastoma Reveals Prognostic and Targetable Tissue States.” http://dx.doi.org/10.1101/2021.07.06.451295.
Steen, Chloé B., Chih Long Liu, Ash A. Alizadeh, and Aaron M. Newman. 2020. “Profiling Cell Type Abundance and Expression in Bulk Tissues with CIBERSORTx.” In, 135–57. Springer US. https://doi.org/10.1007/978-1-0716-0301-7_7.
Trapnell, Cole, Davide Cacchiarelli, Jonna Grimsby, Prapti Pokharel, Shuqiang Li, Michael Morse, Niall J Lennon, Kenneth J Livak, Tarjei S Mikkelsen, and John L Rinn. 2014. “The Dynamics and Regulators of Cell Fate Decisions Are Revealed by Pseudotemporal Ordering of Single Cells.” Nature Biotechnology 32 (4): 381–86. https://doi.org/10.1038/nbt.2859.

Citation

BibTeX citation:
@misc{harbour2023,
  author = {Harbour, Nicholas and Curtin, Lee and Chappell, Michael and
    Hubbard, Matthew and Swanson, Kristin and Owen, Markus},
  title = {Mathematical Modelling of Interacting Sub-Populations in
    Glioblastoma},
  date = {2023-05-01},
  langid = {en}
}
For attribution, please cite this work as:
Harbour, Nicholas, Lee Curtin, Michael Chappell, Matthew Hubbard, Kristin Swanson, and Markus Owen. 2023. “Mathematical Modelling of Interacting Sub-Populations in Glioblastoma.”