gQSPSim: A SimBiology-Based GUI for Standardized QSP Model Development and Application

CPT Pharmacometrics Syst Pharmacol. 2020 Mar;9(3):165-176. doi: 10.1002/psp4.12494. Epub 2020 Mar 10.

Abstract

Quantitative systems pharmacology (QSP) models are often implemented using a wide variety of technical workflows and methodologies. To facilitate reproducibility, transparency, portability, and reuse for QSP models, we have developed gQSPSim, a graphical user interface-based MATLAB application that performs key steps in QSP model development and analyses. The capabilities of gQSPSim include (i) model calibration using global and local optimization methods, (ii) development of virtual subjects to explore variability and uncertainty in the represented biology, and (iii) simulations of virtual populations for different interventions. gQSPSim works with SimBiology-built models using components such as species, doses, variants, and rules. All functionalities are equipped with an interactive visualization interface and the ability to generate presentation-ready figures. In addition, standardized gQSPSim sessions can be shared and saved for future extension and reuse. In this work, we demonstrate gQSPSim's capabilities with a standard target-mediated drug disposition model and a published model of anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) treatment of hypercholesterolemia.

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Computer Simulation
  • Drug Development / instrumentation
  • Drug Discovery / instrumentation
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Models, Biological
  • PCSK9 Inhibitors
  • Proprotein Convertase 9 / drug effects*
  • Reference Standards
  • Reproducibility of Results
  • Software
  • Uncertainty
  • User-Computer Interface
  • Workflow

Substances

  • Antibodies, Monoclonal, Humanized
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9