Core of FindSim

The core FindSim program performs the workflow above: It takes a model, and runs an experiment on it. It reports how well the model output matches the experimental readouts. When run in console mode, it can plot out the experimental and simulated results. It can also run in batch mode, and as a subsidiary program for other tools.-

- Model definition:  FindSim uses MOOSE to run these models and you can use MOOSE scripts for the model definition.More conveniently, the format SBML supports signaling pathway models. Most of the ongoing FindSim projects operate at this level. Many tools support SBML model definition, including MooseGui.

- Experiment definition: This is a structured way to define an experiment and how to run it in FindSim. It has 5 parts:

  •  Metadata
  • Experimental context
  • Experimental input
  • Experimental Readouts and
  • how to map the model to experimental quantities

This can be stored in a Tab Separated Value (tsv) format compatible with spreadsheets and databases. There is now a substantial of such FindSim experiment definitions. The recommended way to codify an experiment is to use.

The current FindSim (version 1.1) supports the following kinds of experiments:

  • Time-series: Stimuli are given at defined times, and the time-course simulation variables is monitored. Stimuli can be in the form of chemical signals or electrical current, voltage, or synaptic inputs.
  • Dose-response: A stimulus (typically molecule) is held fixed at a series of values and the response is monitored for each input value.
  • Bar charts: A number of input changes, typically molecular activators or blockers, are given in any combination, and the steady-state value of the output is plotted for each case as a bar chart.
  • Current clamp: A specified current is delivered at the neuronal soma, and the resulting somatic voltage is recorded, The input voltage can be changed over the course of the simulation.
  • Voltage clamp: A specified voltage is delivered at the neuronal soma, and the current required to hold this potential is recorded, The input voltage can be changed over the course of the simulation.
  • Synaptic input: A specified set of receptors can receive synaptic input at defined times and frequencies.

- Readouts: FindSim 1.1 supports the following readouts

  • Molecule concentrations (absolute and ratio to a reference)
  • direct parameter values in model
  • membrane potential in different parts of the cell
  • holding current for voltage clamp
  • field potentials.

- Model mapping and modification: FindSim allows us to uniquely identify any component of the simulation, so as to control or read out its values.

  • Identified entities, such as membrane potential, can be selected for readout and comparison with experiment.
  • Identified entities, such as molecules, can have be assigned a series of concentration values to represent experimental inputs.
  • One can modify identified entities in a simulation (such as a molecule or reaction) by changing their default value
  • One can even delete individual entities, or groups of entities, or even entire pathways from the model.