In silico Biochemical Reaction Network Analysis (IBRENA)

Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools and Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract IBRENA (In silico Biochemical Reaction Network Analysis) is a software package which facilitates multiple functions including cellular reaction network simulation and sensitivity analysis (both forward and adjoint methods), coupled with Principal Component Analysis (PCA), singular-value decomposition and model reduction.

Cellular reaction networks, for example models of signal transduction, can be simulated when biochemical information about the nature of protein interactions, and kinetic information about individual rate constants/enzyme kinetics is available.

While the above information may be inferred using independent, isolated biochemical assays, In silico simulations combined with cell-based assays help test the degree to which ex vivo measurements translate to the real cellular environment.

IBRENA features a graphical user interface (GUI) that aids simulation and plotting of In silico results. While the primary focus is to aid formulation, testing and reduction of theoretical biochemical reaction networks, the software can also be used for analysis of high-throughput genomic and proteomic data.

Overall, IBRENA enables --

1) Conversion of Comma-Separated Values (.csv) format input files to Systems Biology Markup Language (SBML) format output.

2) In silico dynamic simulation of reaction networks.

3) Identification of critical rate-limiting or regulatory reactions (or species) using sensitivity analysis. Both forward and backward (adjoint) sensitivity analysis can be performed using this software.

Output M-files are also generated for both types of sensitivity analysis.

These M-files may be used by the user for additional user-specific analysis, if necessary, using the array of functions available in MATLAB.

4) Analysis of dynamic simulation or sensitivity coefficient data to decipher the connectivity between the reactions or species. Such analysis is performed using PCA and Singular Value Decomposition (SVD).

5) Model reduction by combining sensitivity analysis with flux analysis.

IBRENA Unique Feature(s) -

The coupling of forward sensitivity analysis with multivariate analysis techniques, especially PCA and SVD, is a unique feature of this software.

In addition, this software features adjoint sensitivity analysis and model reduction methods.

Overall, the compilation of individual routines into a suite with focus on post-simulation analysis is a useful tool for the identification of rate-limiting reactions/species, automated determination of connectivity between the reactions/species, and model reduction.

IBRENA Implementation --

IBRENA is a mixed-language program using MATLAB and FORTRAN.

While simple matrix computations and the GUI interface are coded in MATLAB, FORTRAN in some instances is used to solve Ordinary Differential Equations (ODEs) for enhanced computational efficiency.

The compiling of FORTRAN codes into MATLAB Executable (MEX) file seamlessly links the programming code.

This software is available in two (2) versions:

Detailed differences between the two (2) versions including installation instructions are outlined in Chapter 1 of the manufacturer's software manual.

The software features a GUI with built-in plot panels for rapid visualization and interpretation of results.

Simulation results can also be stored in local files for plotting using other software.

IBRENA has been tested using two In silico biochemical reaction networks that examine Epidermal Growth Factor (EGF) and Tumor Necrosis Factor (TNF) reaction pathways.

Microarray data has been used to test components of the program that relate to multivariate analysis.

Detailed instructions including mathematical derivations and examples are provided with the software. IBRENA has been tested using the Windows operating system.

IBRENA Installation --

IBRENA can be installed either as a stand-alone application or it can be used in the MATLAB environment. Simulation results in both cases can be graphed using IBRENA’s built-in plot functions, or these results can be exported in comma delimited files for analysis in MATLAB or elsewhere.

Stand-alone application -

The stand alone application is easy to install and use. This version does Not require installation of either the SBML or SUNDIALS toolbox (see below...).

All inputs for the stand-alone application are provided using .csv input files.

This partially installed version of the software can handle elemental reactions but Not more complex reactions.

Full Version of the application -

The complete version of IBRENA that is run in the MATLAB environment, can handle any general reaction network that is described by SBML type input file(s) and can be processed using the SUNDIALS package.

This version requires installation of the SBML and SUNDIALS toolboxes to solve arbitrary reactions.

SUNDIALS toolbox --

SUNDIALS (SUite of Nonlinear and DIfferential/ALgebraic equation Solvers) consists of the following five (5) solvers:

1) CVODE - solves initial value problems for ODE systems.

2) CVODES - solves ODE systems and includes sensitivity analysis capabilities (forward and adjoint).

3) IDA - solves initial value problems for Differential-Algebraic Equation (DAE) systems.

4) IDAS - solves DAE systems and includes sensitivity analysis capabilities (forward and adjoint).

5) KINSOL - solves nonlinear algebraic systems.

IBRENA Documentation --

The manufacturers provide an extensive User Manual for IBRENA.

System Requirements

Contact manufacturer.


Manufacturer Web Site IBRENA

Price Contact manufacturer.

G6G Abstract Number 20633

G6G Manufacturer Number 104232