In DENIS@home you can run different research projects. Each one uses a different application that you can choose to run or not. In the following sections you will be able to learn a bit of each one.

• Beta of DENIS-myocyte (DENIS_Myocyte_Beta): Beta version of the simulator used in all the projectsDENIS@home. Every modification of the simulator is tested under this application.
• New human ventricular cell model (NHuVe): Development of a new version of the model proposed by Carro et. al (2011).
• Human ventricular cell models optimization (HuVeMOp): Optimization of the public and most used human ventricular cell models for the representation of electrophysiological markers.

Every project in DENIS@home uses the DENIS-Myocyte simulator. This program permits to simulate any model described following the CellML standard

To thank the altruism of testing the app, all volunteers who run the beta app get a special badge:

Models of Action Potential (AP) have been largely used to study the behavior of the heart in normal or pathological conditions. One of the problems to develop these models is the difficulty to validate the model against all the known experimental situations.

On the other hand, manytimes we need to asume that the model variables are independents. As our previous research shows, this assumtion could be a problem (Carro et. al 2014, Carro et. al 2017). Both problems together makes very difficult to modify a model, because in the moment you change something, many other things will change.

Actually, we are working on an optimization algorithm based on response surface aproximations to calculate the value of parameters of the model that can't be measured directly (Carro et. al 2018). We simulate the cell under different protocols of stimulation and with different combination of the parameters to look for the combination that better represent the experiments. By doing it, we are able to modify several parameters at the same time, not one at a time.

We are developing a new version of the Carro et. al (2011) model and we want to increase the number of parameters we can modify and the number of protocols we can test, but we need to make a lot of simulations.

Phases

• Identification of the shape problem cause (completed)
• Modification of the model to solve the shape problem (completed)
The results of this phases was publised on the conference EMBEC 2017: Multiscale Methods for Definition of Ionic Variables in Electrophysiological Models
• Identification of the restitution problem cause (completed)
• Modification of the model to solve the restitution problem (completed)
• Optimization of ionic conductances to fit physiological markers (completed)
• New version of the optimization to try to fit better the physiological markers (ongoing)

Human ventricular cell models optimization (HuVeMOp)

In the recent years, several human ventricular cell models have been proposed. Although some parts of the models have a similar structure, others are completely different. Also, since the models are made at times when the experimental evidence is different, and sometimes each one uses different data sets, each model could be optimized for different circunstances.

What happens if different models are optimized with the same data? What happens if we redefine the rol of the different currents each model has? The currents will be the same as in the original model, but, are the differences caused by the current or by its role? We want to analyze this.

To be able to compare the models in this ways, we need to apply the our optimization algorithm to all of them (Carro et. al 2018). This study is a first step to a new paradigme of evaluation of the definition of the currents: multimodel validation. But, to be able to do this, first we need to have comparable models

The models that are been optimized in this project are:

• TP06: Alternans and spiral breakup in a human ventricular tissue model. K. H. W. J. ten Tusscher and A. V. Panfilov, 2006. American Journal of Physiology-Heart and Circulatory Physiology 291:3, H1088-H1100
• GPB: A novel computational model of the human ventricular action potential and Ca transient, E. Grandi, F.S. Pasqualini, D.M. Bers, 2010. Journal of Molecular and Cellular Cardiology, volume 48, 112-121. PubMed ID: 19835882
• CRLP: A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions. J. Carro, J.F. Rodríguez, P. Laguna and E. Pueyo, 2011. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. Volume 369, Issue 1954. doi: 10.1098/rsta.2011.0127
• ORd: Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. T. O'Hara, L. Virág, A. Varró, Y. Rudy, 2011. PLOS Computational Biology 7(5): e1002061. doi:10.1371/journal.pcbi.1002061