A semantics, energy-based approach to automate biomodel composition

Abstract

Hierarchical modelling is essential to achieving complex, large-scale models. However, not all modelling schemes support hierarchical composition, and correctly mapping points of connection between models requires comprehensive knowledge of each model’s components and assumptions. To address these challenges in integrating biosimulation models, we propose an approach to automatically and confidently compose biosimulation models. The approach uses bond graphs to combine aspects of physical and thermodynamics-based modelling with biological semantics. We improved on existing approaches by using semantic annotations to automate the recognition of common components. The approach is illustrated by coupling a model of the Ras-MAPK cascade to a model of the upstream activation of EGFR. Through this methodology, we aim to assist researchers and modellers in readily having access to more comprehensive biological systems models.Author summaryDetailed, multi-scale computational models bridging from biomolecular processes to entire organs and bodies have the potential to revolutionise medicine by enabling personalised treatments. One of the key challenges to achieving these models is connecting together the vast number of isolated biosimulation models into a coherent whole. Using recent advances in both modelling techniques and biological standards in the scientific community, we developed an approach to integrate and compose models in a physics-based environment. This provides significant advantages, including the automation of model composition and post-model-composition adjustments. We anticipate that our approach will enable the faster development of realistic and accurate models to understand complex biological systems.

SBML to bond graphs: from conversion to composition

“…Although we merge bond graph modules, the result of the model composition is a single (flattened) bond graph model. We have performed the composition using the approach introduced in [24] with some improvements and added features: SBML support: Since the framework was initially developed for CellML models, we slightly modified it to load and extract information from SBML models; Processed data: To help couple models together, we added the units unification and scaling modules to the framework to help with model composition as discussed in Section 2.3, step 2 of the workflow. After unit unification, the user can select a scaling index for any of the models.…”

“…Although we merge bond graph modules, the result of the model composition is a single (flattened) bond graph model. We have performed the composition using the approach introduced in [24] with some improvements and added features:…”

“…To address this issue, we employed our previously developed framework using bond graphs to compose CellML models and modified it for use with SBML models [24].…”

“…Henceforth, we refer to the former as the pyruvate distribution model and the latter as the PPP model. We have integrated these models into one composite model using our previously developed method in [24].…”

“…In the SHMC package, such changes in equations are not applied automatically and difficult to write manually. To address this issue, we employed our previously developed framework using bond graphs to compose CellML models and modified it for use with SBML models [24].…”