## COPASI

** Category** Cross-Omics>Pathway Analysis/Tools

** Abstract** COPASI (COmplex PAthway SImulator) is a software
application for the simulation and analysis of biochemical reaction
networks.

COPASI supports non-expert users by, for example, automatically converting reaction equations to the appropriate mathematical formalism [ordinary differential equations (ODEs) or reaction propensities].

COPASI is a stand-alone program that can be used through two (2) different executable versions -- a graphical user interface (CopasiUI) and a command line version (CopasiSE) that only contains the calculation engine. CopasiSE is intended for situations in which the user is Not expected to interact with the software.

Essentially, CopasiSE allows much flexibility of execution and control, with the penalty that this version can only run numerical procedures, Not edit models.

CopasiUI, on the other hand, is the complete version of the program and is the one that the manufacturer expects users to run most often.

CopasiUI provides a full graphical user interface (GUI), including functions for creating and editing models and plotting results.

In terms of execution of the numerical procedures (simulation, optimization, etc.) the two (2) versions are essentially equal, except that CopasiUI may be slightly slower when producing graphical output. In practice the two (2) executables share the same source code and are expected to produce exactly the same results.

COPASI's GUI is similar to Windows Explorer in operation, where there is a vertical window on the left with a set of functions organized in a hierarchical way; on the right there is a larger window that contains all of the controls to operate the function selected on the left.

The major group of functions in the program is as follows:

1) Model - where the model can be edited and viewed according to a biochemical or mathematical perspective.

2) Tasks - consisting of the major numerical operations on the model: steady state, time course, stoichiometry, metabolic control analysis and Lyapunov exponents. Below each task an entry with results will appear after the task has been run.

3) Multiple Tasks - which are operations repeating elementary tasks: parameter scanning, optimization and parameter estimation.

4) Output - is where plots and reports are defined and listed.

5) Functions - containing the mathematical functions available, such as the rate laws.

Model editing -- is done through tables and specialized widgets and the program provides various ways of editing the model items.

For example, the user can change the value of kinetic constants in the single reaction widget (which provides detailed information about a single reaction), or in the parameter overview widget.

There are two (2) major views of the model: one set of widgets provides a view from the biochemical perspective, where the model is composed of reactions, compartments, metabolites, etc.; while another provides a mathematical view, where the model is composed of variables and differential equations.

Kinetic Functions -- When a kinetic function is entered (or chosen from the integrated kinetics library) COPASI determines the units of the kinetic parameters from an analysis of the rate law, where possible.

This allows the user to easily determine if available kinetic parameters from one source match a kinetic function from another source.

File Formats -- COPASI's native file format is based on XML and documentation of its schema is available so that other tools can read or write it. COPASI can also read Gepasi files, providing backwards compatibility with its predecessor.

COPASI is able to import Systems Biology Markup Language (SBML) either level 1 or level 2, and thus it can obtain models from many sources, such as other simulators, model databases, pathway databases, etc.

Report Files and Plots -- COPASI can output results of its various functions in two (2) ways: report files and plots.

COPASI supports x–y line plots and distribution histograms, scales can be linear or log-transformed, and the plot window allows zooming and panning.

Optimization Algorithms -- COPASI is equipped with a number of diverse ‘optimization algorithms' that can be used to minimize or maximize any variable of the model, following the scheme proposed by Mendes and Kell (1998).

Two algorithms are based on estimating derivatives of the objective function, steepest descent and Levenberg-Marquardt (Levenberg, 1944; Marquardt, 1963; Goldfeld et al., 1966); a direct search algorithm, which is based on geometric concepts, the Hooke-Jeeves method (Hooke and Jeeves, 1961); four evolutionary algorithms, evolutionary programming (Fogel et al., 1992), 'genetic algorithm' [a version with floating point encoding; Michalewicz (1994)], evolution strategy with stochastic ranking (SRES; Runarsson and Yao, 2000) and a ‘genetic algorithm’ with stochastic ranking; finally, there is also a simple random search algorithm.

The optimization algorithms are also used for estimating parameter values that best fit a set of data provided by the user.

To this end, COPASI reproduces the functionality of Gepasi (Mendes and Kell, 1998) and exceeds it by allowing mixtures of time course and steady-state data to be used simultaneously (Gepasi could only deal with one (1) of these types of data at a time).

Finally, COPASI is able to compute the Lyapunov exponents and the divergence of a given system.

A complete list of all current features/capabilities (including features already stated above) is shown below:

Model --

1) Chemical reaction network;

2) Arbitrary kinetic functions;

3) ODEs for compartments, species, and global quantities;

4) Assignments for compartments, species, and global quantities; and

5) Initial assignments for compartments, species, and global quantities.

Analysis --

1) Stochastic and deterministic time course simulation;

2) Steady state analysis (including stability);

3) Metabolic control analysis/sensitivity analysis;

4) Elementary mode analysis;

5) Mass conservation analysis;

6) Calculation of Lyapunov exponents;

7) Parameter scans;

8) Optimization of arbitrary objective functions; and

9) Parameter estimation using data from time course and/or steady state experiments simultaneously.

Graphical User Interface (CopasiUI) --

1) Sliders for interactive parameter changes; and

2) Plots and Histograms.

Command Line (CopasiSE) for batch processing.

SBML import (L1V1+2, L2V1-3) and export (L1V2, L2V1-3).

Product allows the loading of Gepasi files.

Can export to Berkeley Madonna, XPPAUT, and the C source code of the ODE system can be generated from the model.

*System Requirements*

COPASI runs on MS Windows, Linux, Mac OS X, and Solaris SPARC.

*Manufacturer*

- The COPASI project is an international collaboration between three (3) groups:
- the Virginia Bioinformatics Institute,
- the University of Heidelberg, and
- the University of Manchester.
- The project has also been developed at EML Research gGmbH in the past.

** Manufacturer Web Site** COPASI Project

** Price** A non-commercial license is free. A single COPASI commercial
license is priced at $900.

** G6G Abstract Number** 20296

** G6G Manufacturer Number** 102881