TIde

TIde is a tool for the automatic identification of drug targets in kinetic network models given in the popular SBML format. It is developed by Marvin Schulz at the Theoretical Biophysics group (Humboldt University Berlin).

Install

In case you want to use ParallelPython, you can set the use_parallel option to 1 and add available servers to the servers file. The lines in the file are statements of the form ip,computer_name,number_of_cpus_to_be_used. Then in a seperate TIde session you

How to use

First you have to start TIde with the launcher from Applications/System Tools. (Alternatively you can hit Alt-F2 and then type xterm -e "cd /usr/lib/python2.5/site-packages/TIde && sudo bash".) For the analysis of a single file you have to call python model.py -f path_to_model in the TIde main directory including the options
optionmeaningexampleoptional/mandatorydefault
-aObservable, e.g. species_1 which is accumulating in the pathological statespecies_1mandatory
-sModel is a signalling pathway optional
-iDifferent effective inhibitor concentrations0.1,1,10optional0.1
-gUse only certain reactions as possible modification targetsreaction_0,reaction_1optionalall
-lUse up to this many modifications simultaneously2optional1
-tDo the computation by a simulated titrationoptional
-eEstimate effective inhibitor concentrations to achieve a reduction of the aim value to this factor.0.1optional

After all computations have been performed you can call different output methods, e.g. html.py, htmllist.py, or pdfplot.py. The first argument to the tools is the name of the output file which has to be placed in the folder named after the model which was created in the previous step. E.g. python html.py models/simple_signalling_model/sdh will create the file models/simple_signalling_model/sdh.html. The options for html.py are
optionmeaningexampleoptional/mandatorydefault
-iIgnore lines containing the strings or lacking the strings, e.g. show only combinations including reaction_3 but ignore entries with the effective inhibitor concentration of 0.375.^reaction_3,0.375optional
-sIgnore control/response coefficients in the output. optional

while the options for pdfplot.py are
optionmeaningexampleoptional/mandatorydefault
-rRange of the x axis1,100optional
-xTake only curves whichs name matches this regular expression".*(1|5).*n$"optional.*

Another interesting script for analysing data of a 2-dimensional scan for good inhibition targets is sdhanalysis.py. With its help synergisms and antagonisms in the inhibition results can be revealed. The command line options for this script are
optionmeaningexampleoptional/mandatorydefault
-tThreshold how much stronger a synergism has to be compared to the sum of single effects5optional1
-vVerbosity1optional0

Questions?

You can contact the author of this software under marvin.schulz@biologie.hu-berlin.de.

Commands for reproduction of the figures and results in the article

python model.py -f models/prebranch_vf_10.xml -a species_7 -l 2 -i 0.1
python html.py models/prebranch_vf_10/sdh -i "uncom, com,7"
python model.py -f models/postbranch_vf_10.xml -a species_7 -l 2 -i 0.1
python html.py models/postbranch_vf_10/sdh -i "uncom, com,7"
python model.py -f models/BIOMD0000000211.xml -a vHK -t -i 1000
python pdfplot.py -f models/BIOMD0000000211/sdh -x vHK
python pdfplot.py -f models/BIOMD0000000211/sdh -x non
python model.py -f models/BIOMD0000000211.xml -a vHK -i 100 -l 2
python sdhanalysis.py models/BIOMD0000000211.sdh
where the html.py and pdfplot.py calls will produce HTML and PDF files in the models/MODELNAME/ directory.