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Introduction

What is EARM?

The Extrinsic Apoptosis Reaction Model (EARM), is a family of novel and previously published models of extrinsic apoptosis, focusing on variant hypotheses for how the Bcl-2 protein family regulates mitochondrial outer membrane permeabilization (MOMP). All models are written using the Python software framework PySB.

The models in this Python package implement 15 different mechanistic hypotheses for MOMP regulation by the Bcl-2 protein family, including

  • 3 novel MOMP models of expanded scope that are unique to EARM and are described in Lopez et al. (2013), ([Lopez2013]_)
  • 5 MOMP models with hypothetical reaction topologies previously described in Albeck et al. (2008) PLoS Biology, Figure 11 ([Albeck2008]_)
  • 6 MOMP models drawn from three papers from the research group of Pingping Shen ([Chen2007biophysj]_, [Chen2007febs]_, [Cui2008]_)
  • 1 MOMP model focusing on Bad phosphorylation drawn from Howells et al. (2011), J. Theor. Biol. ([Howells2011]_)

Moreover, for each of these there is a MOMP-only ("mito") version of the model and a full-apoptosis version of the model, in which the MOMP model is linked to the upstream and downstream pathways of extrinsic apoptosis from the previously published EARM 1.0 from [Albeck2008]_. This gives a total of 30 different models.

Goals

Our goals in creating EARM were to:

  • Create a newly updated model of the extrinsic apoptosis pathway incorporating current knowledge of Bcl-2 interactions and MOMP mechanism
  • Demonstrate the use of PySB for transparent and reusable model development
  • Make previous apoptosis modeling work from the community available for reuse in a common format
  • Explore approaches for working with, and discriminating among, multiple hypotheses for biological mechanisms
  • Engage the modeling community in a pilot effort to use software engineering tools and approaches for incremental, collaborative model development.

Installation

EARM requires PySB, but itself is pure Python (i.e., does not require installation or compilation of dependencies written in languages other than Python). PySB is available at http://pysb.org and http://github.com/pysb/pysb. EARM has its own website at http://sorgerlab.github.com/earm.

Note

The PySB VM includes EARM!

If you are using PySB via the downloadable virtual machine, EARM is already installed.

You can get the latest version of EARM from GitHub at http://github.com/sorgerlab/earm. If you are a Git user you can get the source code with:

git clone https://github.com/sorgerlab/earm.git

which will create a directory called earm containing all EARM files.

If you are not a Git user you can download a ZIP file at https://github.com/sorgerlab/earm/zipball/master.

Once you have downloaded the EARM source code, install EARM by switching to the top-level EARM source directory and running:

python setup.py install

How to use the documentation

In addition to this introduction, a general description of how the model implementations are organized into Python modules can be found in the :doc:`models`.

More detailed descriptions of each model, with links to the Python source code that serves as the actual model specification, can be found at :doc:`modules/index`.

In addition to the model specifications, EARM also contains a set of tests that can be run to ensure that the models can be successfully loaded and that the PySB re-implementations of previously published models exactly match their prior implementations (specified as systems of ordinary differential equations). Documentation and code for these tests can be found at :doc:`tests/index`.

Staying current

This package is subject to change. In particular it may be refactored to stay current with ongoing updates to PySB, or to add new models and fix errors in existing ones. To be notified of updates, follow EARM on GitHub at http://github.com/sorgerlab/earm. If you use Git, you can get updates by going to the EARM source directory and running git pull. After getting the update source code, you will need to re-install by running python setup.py install.

Contributing

If you find bugs or errors, please notify us by submitting issues to the EARM issues page on GitHub.

Also, we welcome contributions from other researchers studying extrinsic apoptosis! To contribute, fork EARM on GitHub and make your revisions and additions. To request that your contributions be incorporated in the EARM repository, submit a pull request.