title: Integrating multi-scale data to create a virtual physiological mouse heart.
abstract: While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human- and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle.
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK ; Biomedical Engineering Department, King's College London, London, UK.
authors.forename: Sander
authors.initials: S
authors.lastname: Land
authors.affiliation: Biomedical Engineering Department, King's College London, London, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Niederer
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway ; KG Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: William E
authors.initials: WE
authors.lastname: Louch
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway ; KG Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ole M
authors.initials: OM
authors.lastname: Sejersted
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, UK ; Biomedical Engineering Department, King's College London, London, UK.
authors.forename: Nicolas P
authors.initials: NP
authors.lastname: Smith
keywords: cardiac multi-scale model; genetic knockout studies; heterogeneous length-dependent activation; mouse modelling; parameter sensitivity