MIDIA Software (v1.1)

OVERVIEW OF HOW TO USE MIDIA

First read the Application Note on the MIDIA software:
Bowsher, C.G. Automated analysis of information processing, kinetic independence and modular architecture in biochemical networks using MIDIA (Bioinformatics, 2011: 27)
The following guidance is supplementary.

MIDIA is designed for the study of biochemical reaction networks. However, general biomolecular networks (e.g. PINs, GRNs) that may be represented as directed or undirected graphs are also supported. Such general networks should be input using the corresponding undirected graph as the input variable uG (see tutorial example).

A biochemical reaction network is input to MIDIA using the matrices mS,mR, and mP which correspond to the quasi-stoichiometric, reactant and product matrices respectively. Each matrix must have row names corresponding to the names of the biomolecular species and column names corresponding to the reaction 'names'.

mS each entry indicates whether a species is overall consumed (-1), produced (+1), or unchanged (0) by the reaction that corresponds that entry's column. Alternatively, a full stoichiometric matrix may be inputted: this is not required for the validity of the results but the extra information provided refines the T_M computed (and associated Input-Output paths).
mR each entry indicates whether a species is a reactant (1) or is not a reactant (0) in the relevant reaction;
mP each entry indicates whether a species is a product (1) or is not a product (0) in the relevant reaction.

For some reaction networks, mR=mS<0 and mP=mS>0, but this is not always the case. User specification of the reactant and product matrices is therefore recommended. Reaction networks available in SBML (such as those of the Biomodels Database) may be imported using the supplied R function mRmSmPfromSBML(.) which returns the required matrices mS, mR, and mP. For example, the calls to create the matrices mRMAPK and mSMAPK from the original, SBML description of the MAPK network (Section 2) would, with prior installation of rsbml, be:
library(rsbml)
mRmSmPMAPK = mRmSmPfromSBML("/MIDIA","BIOMD0000000011.xml")

MIDIA has 2 MODEs of operation. The first is designed to analyse INFO(rmation)PROCESSING by the reaction network. The second has a less specialised focus, providing modularisations based on (local) kinetic independence (T_MI), more general graphical separation (again denoted T_MI), or conditional independence of module trajectories (T_M). NB: For networks not specified in terms of reactions, the graphical separations implied by T_MI should be seen as the absence of direct effects in the graph (themselves appropriately interpreted), as opposed to the absence of direct (mass-action) kinetic effects.

The user may select one of 4 output types (using OutputSelectn) : the Kinetic Independence Graph or KIG; a modularisation based on Instantaneous kinetics (T_MI); a modularisation based on the conditional independence of module trajectories (T_M); or T_M in combination with the Input-Output matrix for analysis of INFOPROCESSING.
The return of the MIDIA(.) function is either the KIG (as a graphNEL object) or a modularisation (as a list). In the latter case the elements of the list are as follows:
T[[1]] gives the network species names
T[[2]] gives the contents of the modules, with modules labelled with their 'clique numbers' (i.e. the original module numbers in the clique tree obtained prior to aggregation);
T[[3]] gives the contents of the edges (with edges identified by the 'child' module of the edge);
T[[4]] gives the 'parent' module of each module in the tree (i.e. the unique, lower numbered module joined to it in the tree);
T[[5]] gives the contents of the module 'residuals' (each module residual consists of the module species, but excluding those species in edges that come out of the module in the tree).

High level control of output plotting is via the PLOT variable. If output is to be plotted (PLOT[1]=TRUE), plotting may be to the screen (PLOT[2]=TRUE) or else to a pdf file (PLOT[2]=FALSE) with user-supplied filename (given by PLOT[3]). Note that the filename used must not be that of an already open pdf file.
Further control over graphics is via the PlotJTree variable and, where required, via inputs to the functions PlotJunctionTree(.) and PlotIOPathMatrix(.) that are called by MIDIA(.).

The input variable InfoProc is a list controlling the options for the analysis of INFOPROCESSING by the reaction network (see Inputs and Outputs). The analysis may be for specified input and output species, or for a group of modules where the aim is, e.g., to analyse information processing between all distinct module pairs of that group.

Coarsegraining is controlled using the input variable Granularity and functions somewhat differently in the 2 different MODEs. Again, see Inputs and Outputs.

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