Model reuse with Cell ML The Sachse myocytefibroblast

Model reuse with Cell. ML: The Sachse myocyte-fibroblast model (3 continents & time zones!) Frank B. Sachse Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, US Catherine Lloyd, James Lawson The Auckland Bioengineering Institute, University of Auckland, NZ Alan Garny Department of Physiology, Anatomy & Genetics, University of Oxford, UK

Cardiac modeling and simulation Intracellular signaling Excitation-contraction coupling Effects of ion channel mutations Intercellular electrical signaling Spread of excitation in cardiac tissue Myocyte-fibroblast interactions Basic building blocks for modeling Models of cells (Systems of ordinary differential equations) Models of ion channels Research is based on previously developed models. Significant effort spent in re-implementation of models. G. Gaudesius et al. Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circ. Res. , 93: 421 -428, 2003.

Step 1: Catherine Lloyd (Auckland) translated the fibroblast model into Cell. ML… ~ 3 hours (Sachse et al. , Ann Biomed Eng, 36(1): 41 -56, 2008)

Step 2: Frank Sachse (Utah) took the existing Pandit myocyte model from the Cell. ML Model Repository and further curated it… with a little help from Alan Garny (Oxford)… ~ 2 -3 days (Pandit et al. , Biophys J, 81(6): 3029 -51, 2001)

Step 3: Frank Sachse (Utah) merged the Pandit myocyte model with the fibroblast model to produce a coupled myocyte-fibroblast model… ~ 2 days

Step 4: Model Curation Catherine Lloyd (Auckland) used the simulation tools PCEnv and COR to curate the coupled model – removing duplicated connections, fixing unit definitions, etc… ~ 1 hour With the help of Frank Sachse (Utah), James Lawson (Auckland) fixed the units so the model ran in all three simulation tools – JSIM, PCEnv and COR… ~2 -3 days

Step 5: James Lawson (Auckland) created a PCEnv session file for the coupled model… ~ 4 hours

Step 6: (Future) Decomposition of the coupled myocytefibroblast model and its translation into Cell. ML 1. 1 +

… which will facilitate the duplication of the fibroblast model and the connection of multiple cells + + +

Step 7: (Future) And even further decomposition of the model into its constituents - channels, pumps, and intracellular calcium fluxes - as we build a library of reusable components.

Acknowledgments Frank Sachse (Utah) Catherine Lloyd (Auckland) James Lawson (Auckland) Alan Garny (Oxford)