## Technical requirements: The script was built using Python 2.7 version. It is possible that the most recent version (from 3.x on) requires modifications. Libraries required: deafault for Python package: csv codecs xml (xml.dom.minidom and xml.etree.ElementTree) os string sys integrated in the sub-folder PythonModules boolean2 ('Boolean network simulations for life scientists', Albert I et al, Source Code for Biology and Medicine, 2008) xlrd ## Available files: Simulation_START.py : file to start the simulation. It contains the path to files required for the simulation (CellDesigner XML, Boolean text, Species CSV) TO RUN A SIMULATION: enter the file, comment all scenarios except the one of interest; knockout variation of scenario 1: the user can modify the lists of active and inactive genes; SimulationMacroph.py : modulation of simulation parameters. There are two consecutive simulations active: the first one is 11 iterations long and represents the stimulation phase, while the second one is 14 iterations long and describes the behavior of the model when the stimulus is absorbed. The user can modulate the simulation by increasing the number of iterations ('steps = 11'), by modifying the update of the elements of the model ('sync' to 'async'), focus on the continuous stimulus by commenting line 67, 68, and 69. This file can also generate new CellDesigner XML files, where genes, proteins and miRNAs are colored according to their activation state (lines 72-85). Currently, two files are generated: one describes the initial conditions ('initialState.xml'), and the other the final state of the model after the declared number of iterations ('finalState.xml'). changinColor.py : setting the color of the elements contained in CellDesigner XML file according to the activation state of each element. itemSelection.py : in agreement with the map-designer expert, some elements of CellDesigner XML map are drawn exclusively for the simulation. If present, these elements and their reactions are colored differently. The different color code allows the script to easily identify these elements, perform the simulation, and present 'finalState.xml' and 'initialState.xml' maps without the simulation's elements. InitConsSetMactoRed.py : initialization of the elements of the model according to the category they belong to. StrongInhibition.py : revision of the Boolean model file: merging rules defining the state of the same element and setting the strength of the inhibition. Even if from the biological point of view it may not be correct, we assume that the activity of one inhibitor is strong enough to stop the reaction. In addition, multiple Boolean rules determining the state of one element are correlated with 'OR' function. ReactionTextCreator.py : extraction of the relevant elements and their reactions from the CellDesigner XML file and the CSV file to generate the equivalent Boolean model of the CellDesigner map. Every reaction is analyzed independently, and the file generated may include multiple rules for one element. SpeciesTable.py : extracting the main information about the elements presented in CellDesigner XML file. Each element is annotated with the correspondent molecular species, two identifiers, MIRIAM annotations, and the color. These information are stored in a separate CSV file, automatically generated by the code. 2015-08-03_infection_macrophage_part-for-review.xml : CellDesigner XML file for the map. To visualize it as a real biological representation and not as XML file, it is necessary to download the free available software CellDesigner, v4.3 or v4.4. (http://www.celldesigner.org/) ## GIFs for Scenario 1, 2 and 3 simulations Tested on Chrome and Mozilla Firefox: open a new window press 'Ctrl' and 'O' select the GIF file The same procedure should be valid for latest versions of Internet Explorer (v10 or later).