Multi-Objective Calibration Paper Published in Royal Society Interface

For a while now we have been working with Mark Read (now at the University of Sydney) on the potential to calibrate complex models of biological systems using multi-objective optimisation approaches, such as genetic algorithms. I am pleased to say that a paper describing this work has now been published in the Journal of the Royal Society Interface.

This publication describes the application of the genetic algorithm NSGA-II in calibrating Mark’s model of Experimental Autoimmune Encephalomyelitis that he developed in his PhD, and shows promise in the use of multi-objective optimisation in calibrating model parameters to match expected behaviours, and recalibrating these models should the parameters change.

More information on the model and Mark’s other research can be found on Mark’s website.

Paper Abstract:

Computational agent-based simulation (ABS) is increasingly used to complement laboratory techniques in advancing our understanding of biological systems. Calibration, the identification of parameter values that align simulation with biological behaviours, becomes challenging as increasingly complex biological domains are simulated. Complex domains cannot be characterized by single metrics alone, rendering simulation calibration a fundamentally multi-metric optimization problem that typical calibration techniques cannot handle. Yet calibration is an essential activity in simulation-based science; the baseline calibration forms a control for subsequent experimentation and hence is fundamental in the interpretation of results. Here, we develop and showcase a method, built around multi-objective optimization, for calibrating ABSs against complex target behaviours requiring several metrics (termed objectives) to characterize. Multi-objective calibration (MOC) delivers those sets of parameter values representing optimal trade-offs in simulation performance against each metric, in the form of a Pareto front. We use MOC to calibrate a well-understood immunological simulation against both established a priori and previously unestablished target behaviours. Furthermore, we show that simulation-borne conclusions are broadly, but not entirely, robust to adopting baseline parameter values from different extremes of the Pareto front, highlighting the importance of MOC’s identification of numerous calibration solutions. We devise a method for detecting overfitting in a multi-objective context, not previously possible, used to save computational effort by terminating MOC when no improved solutions will be found. MOC can significantly impact biological simulation, adding rigour to and speeding up an otherwise time-consuming calibration process and highlighting inappropriate biological capture by simulations that cannot be well calibrated. As such, it produces more accurate simulations that generate more informative biological predictions.