## Systems Biology Research Tool (SBRT)

** Category** Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools

** Abstract** The Systems Biology Research Tool (SBRT) is a free, easy-to-use, open-source, integrated software platform that can be used to facilitate the computational aspects of Systems Biology.

The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics.

New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology.

This software can be used to make sophisticated computational techniques accessible to everyone (including those with No programming ability), to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

The SBRT can, for example, be used to translate data files into various machine- and human-readable formats; to simulate the activity of reconstructed signal transduction and genome-scale metabolic networks using flux balance analysis and related methods;

And to analyze the topology of experimentally determined biochemical reaction networks, such as transcriptional regulation and protein-protein interaction networks.

SBRT Implementation -- The SBRT is both an application and an application programming interface (API). The SBRT’s API contains over 300 well tested and fully documented classes and interfaces.

The API is composed of two (2) functionally distinct levels: the kernel, which is responsible for performing all significant computation, and the shell, which is responsible for relaying information between the user and the kernel.

The kernel is completely independent of the shell, which results in a great degree of flexibility and robustness: new functionality can be added to the kernel without concern for user-level I/O details; new functionality can be added to the shell without modifying the kernel, thereby preventing the introduction of kernel-level errors.

The kernel contains implementations of algorithms, methodological procedures, and fundamental objects, such as networks, chemical reactions, mathematical expressions, matrices, convex polytopes, hyper-planes, linear program solvers, etc.

The shell is primarily composed of classes and interfaces for reading (writing) files from (to) the hard drive, for parsing and formatting various types of data, and for managing and monitoring kernel-level activities.

SBRT Use as an application -- The SBRT can be used as an application to execute processes. A process is a series of actions that takes user-supplied input and produces a result.

The SBRT includes 35 processes for analyzing stoichiometric networks, such as optimizing objective functions, computing the variability of fluxes, identifying reaction pathways, generating uniformly distributed points within flux spaces, analyzing the properties of flux vectors and intervals, and more.

The SBRT also includes 16 processes utilizing graph theory, geometry, algebra, statistics, and combinatorics. Descriptions of these 51 processes are as follows:

Flux Optimization --

1) Flux balance analysis (FBA) Optimization - Used to compute the optimal value of a flux or linear combination of fluxes in a stoichiometric network.

2) Reaction Deletion - Used to compute the effect of deleting sets of reactions in a stoichiometric network.

3) Catalyst Deletion - Used to compute the effect of deleting sets of catalysts in a stoichiometric network.

4) Objective Function Analysis - Used to compute the optimal values of multiple objective functions for a stoichiometric network.

5) Constraint Variation - Used to compute the optimal values of a single objective function for multiple sets of flux constraints.

6) Constraint Variation-Reaction Deletion - Used to compute the combined effects of deleting reactions and varying the flux constraints in a stoichiometric network.

7) Constraint Variation-Catalyst Deletion - Used to compute the combined effects of deleting catalysts and varying the flux constraints in a stoichiometric network.

8) Constraint Variation-Objective Function Analysis - Used to compute the optimal values of multiple objective functions for multiple sets of flux constraints.

Flux Variability --

9) Simple Flux Intervals - Used to compute the intervals of fluxes in a stoichiometric network in the simplest possible way.

10) Constrained Reverse Reaction Flux Intervals - Used to compute the intervals of fluxes in a stoichiometric network after constraining the fluxes of reversible reactions.

11) Flux Cap Identification - Used to create caps for each unbounded flux in a stoichiometric network.

12) Mahadevan-Schilling Flux Intervals - Used to compute the Mahadevan-Schilling flux intervals in a stoichiometric network.

13) Constraint Variation-Simple Flux Intervals - Used to compute the simple flux intervals for multiple sets of flux constraints.

14) Constraint Variation-Constrained Reverse Reaction Flux Intervals - Used to compute constrained reverse reaction flux intervals for multiple sets of flux constraints.

15) Constraint Variation-Mahadevan-Schilling Flux Intervals - Used to compute Mahadevan-Schilling flux intervals for multiple sets of flux constraints.

Chemical Reaction Pathway Identification --

16) Extreme Current Identification - Used to identify the extreme currents in stoichiometric networks.

17) WW Network Reduction - Used to reduce the size of stoichiometric networks for the purpose of identifying the cycles they contain.

18) MS Network Reduction - Used to reduce the size of stoichiometric networks for the purpose of identifying the cycles they contain.

19) SLP Cycle Identification - Used to identify the cycles in stoichiometric networks.

Flux Space Sampling --

20) Random Constraint Generator - Used to generate random flux constraints.

21) Random Objective Function Generator - Used to generate random objective functions.

22) Initial Point Generator - Used to compute an initial flux vector for use in CD Hit-and-Run Analysis.

23) Coordinate Direction Hit-and-Run Analysis - Used to compute random, uniformly-distributed flux vectors from the interior flux space.

24) Space Variation-Initial Point Generator - Used to compute initial flux vectors for use in Space Variation-CD Hit-and-Run Analysis.

25) Space Variation-Coordinate Direction (CD) Hit-and-Run Analysis - Used to compute random, uniformly-distributed flux vectors from the interiors of multiple flux spaces.

Flux Data Analysis --

26) Flux Activity Analysis - Used to analyze the activity of fluxes in a collection of flux vectors.

27) Flux Plasticity Analysis - Used to analyze the plasticity of fluxes in a collection of flux interval vectors.

28) Stoichiometric Network Utilities -- Simple Reaction File Reader - Used to translate files containing a list of chemical reactions into human-readable FBA Reaction Files:.

29) Palsson-SBML File Reader - Used to read SBML files from Dr. Palsson’s website.

30) BiGG-SBML File Reader - Used to read SBML files from the BiGG Database - (see G6G Abstract Number 20628).

31) Palsson-SBML File Translation - Used to translate SBML files from Dr. Palsson’s website into human-readable FBA Reaction Files and Reaction-Catalyst Association Files.

32) BiGG-SBML File Translation - Used to translate SBML files from the BiGG Database into human-readable FBA Reaction Files and Reaction-Catalyst Association Files.

33) Metatool File Writer - Used to convert FBA Reaction Files into input files for Metatool.

34) Network Information Gatherer - Used to gather basic information about a stoichiometric network.

35) FBA System Solver - Used to solve the equation Sv = 0.

Graph Theory --

1) Path Identification in a Directed Graph - Used to identify the simple paths in a directed graph.

2) Cycle Identification in a Directed Graph - Used to identify the simple cycles in a directed graph.

Geometry --

3) Coordinate Directions Hit-and-Run -Used to generate random interior points within convex polytopes.

Algebra --

4) Linear System Solver - Used to solve systems of linear equations using Mathematica.

5) Multiple-Vectors File Conversion - Used to convert a single multiple-vectors file into multiple single-vector files.

6) Single-Vector Files Conversion - Used to convert multiple single-vector files into a single multiple-vectors file.

7) Matrix File Conversion - Used to convert a matrix into a list of linear combinations.

8) Linear Combination File Combination - Used to convert a list of linear combinations into a matrix.

Combinatorics --

9) Single-Element Unions - Used to compute single-element unions of collections of sets.

10) Strict Single-Element Unions - Used to compute strict single-element unions of collections of sets.

Statistics --

11) Correlation Estimation - Used to compute a variety of correlation coefficients using R (a programming language).

12) Kendall’s Tau Correlation - Used to compute Kendall’s tau correlation statistics.

13) Mann-Whitney U Test - Used to compute Mann-Whitney U statistics.

General Utilities --

14) Interval Comparison - Used to compare intervals for equality within a given tolerance.

15) Numerical Vector Comparison - Used to compare numerical vectors for equality within a given tolerance.

16) Variable Participation - Used to group mathematical expressions based on the variables they contain.

SBRT Processes --

Processes can be controlled with simple text-based input files (that can be created using common word processing or spreadsheet applications) or directly from the command line. When possible, files generated by one process can also be used as input files in other SBRT processes, allowing the user to design complex analyses by linking processes via their input and output files, without writing a single line of code.

For example, the process BiGG-SBML File Reader can be used to translate a machine-readable file into a human-readable and -editable ‘text file’ R (Not to be confused with the programming language R...) that contains a list of chemical reactions.

The file R can then be supplied to the Network Information Gatherer process to create a text file N that contains the names (or IDs) of all chemical reactions contained in R; and R can also be supplied to the Random Constraint Generator process to create a text file C of randomly generated flux constraints.

The files R, N, and C can then be supplied to the FBA Constraint Variation-Objective Function Analysis process to determine the maximum fluxes of the reactions in R that are denoted in N for each set of flux constraints in C. Each of these files can be edited by the user at any step, and many other combinations of processes are possible.

The use of the SBRT as an application requires No programming ability, and is fully documented in a freely available HTML-based User's Guide, which provides a detailed description of each process and contains hyperlinks to at least one complete example.

*System Requirements*

Contact manufacturer.

*Manufacturer*

- Department of Biochemistry
- University of Zurich
- Zurich, Switzerland
- And
- Swiss Institute of Bioinformatics
- Lausanne, Switzerland

** Manufacturer Web Site**
SBRT

** Price** Free.

** G6G Abstract Number** 20695

** G6G Manufacturer Number** 104269