New models of atherosclerosis and multi-drug therapeutic interventions

• Published in: Bioinformatics Vol. 35; no. 14; pp. 2449 - 2457
• Main Authors: Parton, Andrew, McGilligan, Victoria, Chemaly, Melody, O’Kane, Maurice, Watterson, Steven
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.07.2019
• ISSN: 1367-4803; 1367-4811; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/bty980

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 and Systems Biology Markup Language, 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 Material 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 Supplementary data are available at Bioinformatics online.