New models of atherosclerosis and multi-drug therapeutic interventions.

Andrew Parton, V. E. McGilligan, Melody El Chemaly, Maurice O'Kane, Steven Watterson

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Abstract

Motivation. Atherosclerosis is amongst the leading causes of death globally. However, it is challenging to study in vivo or in vitro and no detailed, openly-available computational models exist. Clinical studies hint that pharmaceutical therapy may be possible. Here we develop the first detailed, computational model of atherosclerosis and use it to develop multi-drug therapeutic hypotheses.

Results. We assembled a network describing atheroma development from the literature. Maps and mathematical models were produced using the Systems Biology Graphical Notation (SBGN) and Systems Biology Markup Language (SBML), respectively. The model was constrained against clinical and laboratory data. We identified five drugs that together potentially reverse advanced atheroma formation.

Availability and Implementation. The map is available in the supplementary information in SBGN-ML format. The model is available in the supplementary material and from BioModels, a repository of SBML models, containing CellDesigner markup.

Supplementary Information. Available from Bioinformatics online.
Original languageEnglish
Pages (from-to)2449-2457
Number of pages9
JournalBioinformatics
Volume35
Issue number14
Early online date6 Dec 2018
DOIs
Publication statusPublished - 31 Jul 2019

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Keywords

  • Systems biology
  • Atherosclerosis
  • Cardiovascular
  • pathways

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