Software
CellNetAnalyzer
Structural and Functional Analysis of Cellular
Networks
1402-3895 GBC
CellNetAnalyzer is a package for MATLAB and provides a comprehensive and
user-friendly environment for structural and functional analysis of biochemical
networks. CNA facilitates the analysis of metabolic (stoichiometric) as well as
signaling and regulatory networks solely on their network topology, i.e.
independent of kinetic mechanisms and parameters. CNA provides a powerful
collection of tools and algorithms for structural network analysis which can be
started in a menu-controlled manner within interactive network maps. Recently,
API functionalities have been added to enable interested users to call
algorithms of CNA from external programs. Applications of CNA can be found in
systems biology, biotechnology, metabolic engineering, pharmacology,
microbiology, chemical engineering.
General Information
CellNetAnalyzer has been developed by Steffen Klamt in the Systems Biology
group of Prof. Ernst Dieter Gilles at the Max Planck Institute for Dynamics of
Complex Technical Systems in Magdeburg.
Delivered will be always the latest version.
The requirements for using CellNetAnalyzer are:
MATLAB version 7.1 (R14) or higher
some functions require the optimization toolbox of MATLAB (or/and
GLPKMEX with GLPK library)
An English manual is available (for an online manual see here).
Detailed Description
For a full description and for latest developments please look at
CellNetAnalyzer's homepage.
CellNetAnalyzer runs under MATLAB and is thus independent of your operating
system. It directly benefits from MATLAB’s built-in functions and the rich
functionalities for building graphical user interfaces. Basically, CellNetAnalyzer
consists of (i) user-defined network projects and (ii) a toolbox with numerous
functions for structural network analysis:
(i) Network projects: are created and designed by the user. A network project is
of type “Mass-flow” (modeling material flows as in metabolic or other
stoichiometric reaction networks) or of type “Signal-flow” (modeling information
or signal flows as in signal transduction networks or regulatory networks). Each
network project contains an abstract (symbolic) network representation as well
as one or several network graphics visualizing the network under investigation.
The abstract network model is composed by declaring network elements such
as reactions or compounds (see Fig. 1 and Fig. 2), whereas the network
graphics have to be imported and thus created by other programs (e.g.
CellDesigner, xfig, CorelDraw etc.; for signal-flow networks, ProMoT provides
Contact
Dr. Bernd Ctortecka
Tel.: 089 / 290919-20
ctortecka@max-pla
an elegant solution to construct network map AND network model (in
CellNetAnalyzer format) in one step). Network model and graphical network
representation can then be linked with the help of user interfaces (text boxes)
leading to interactive network maps. Examples are shown in Fig. 3
[stoichiometric network] and Fig.4: [signal-flow network]. Interactive network
maps are the central components of network projects. The text boxes facilitate
input and output (e.g. of reaction rates) directly within the network visualization.
(ii) The toolbox of CellNetAnalyzer provides functions and procedures which,
depending on the network type, facilitate stoichiometric (metabolic) network
analysis or the analysis of signal-flow networks (see list below). These functions
can be started conveniently by a pull-down menu installed in the network maps
and the user has not to be aware of mathematical details. For speeding up
extensive computations, a few algorithms use the MEX interface of MATLAB to
call precompiled C files. Computed results are displayed in the interactive
maps, different coloration of the text boxes illustrate distinct contexts. For
example, the screen shot in Fig. 3 shows a scenario of metabolic flux analysis
and Fig.4 a path in a signaling network.
From version 7.0, CNA provides an API enabling the exchanging of
data/variables between CNA and user-created functions. User functions can
also be embedded in the CNA menu.
Here is a list of functions provided in CellNetAnalyzer
Mass-flow (stoichiometric, metabolic) networks:
Metabolic flux analysis
classification of flux scenarios (determinacy and redundancy) and rates
(balanceability and calculability)
calculation of flux distributions (for all types of flux scenarios)
consistency checks in redundant systems
flux optimization subject to an arbitrary linear objective function (flux
balance analysis, FBA)
sensitivity analysis of calculated rates
feasibility check of a given scenario
Analysis of basic topological / structural properties
graphical display of the stoichiometric matrix
computation of graph-theoretical path lengths in an directed and
undirected graph representation of the reaction network; determination
of network diameter
detection of (elementary) conservation relations, enzyme subsets,
isozymes, blocked and parallel reactions
connectivity histogram
Metabolic pathway analysis
large-scale calculation of elementary (flux) modes, extreme pathways
and convex bases with new algorithms (optionally, METATOOL can
be used (on the fly) for calculations)
display of computed pathways in the flux maps
selection of pathways with respect to certain criteria
statistical analysis of pathways:
yield histogram; detection of optimal and suboptimal pathways
reaction participation; prediction of mutant phenotypes
quantitative estimating the importance of reactions: controleffective fluxes (CEF)
pathway lengths histogram
xport of computed elementary modes for external analysis
Minimal cut sets
new (structural) approach for analyzing the fragility and for finding
targets in biochemical reaction networks
efficient calculation of minimal cut sets (with respect to a user-defined
set of (target) elementary modes)
display of minimal cut sets within the network graphics
statistical evaluation and assessment of minimal cut sets
Clipboard function; enables also arithmetic ('+','-','\','*') combination of
different flux distributions for comparisons of different scenarios
Comparing fluxes in a bar chart
Network composer (Fig. 1): editing the network structure (with the help of
masks (Fig. 2)
Saving and printing of network maps and/or the values of (computed or
pre-defined) scenarios
SBML import and export; export of the stoichiometric matrix in ASCII
format
Zoom tool (for zooming in and out in large maps)
Others
Signal flow (signalaing, regulatory) networks:
Analysis of interaction graphs
basic topological properties
large-scale computation of all positive and negative signaling paths
connecting inputs with outputs or of all signaling paths between a given
pair of nodes; statistical analysis of these paths
large-scale computation of all positive and negative feedback loops;
statistical analysis of these routes
computation of minimal cut sets (removing reactions or species) for a
given set of paths or/and loops
computation of distance (shortest paths) matrices; separately for
positive and negative paths
large-scale dependency analysis (which species has (positive/negative)
influence on which species; identification of activators and inhibitors of
a given species enabling predictions on perturbation experiments)
Analysis of logical (Boolean) interaction networks
arbitrary logical models (constructed with AND,OR and NOT operators)
with multiple discrete levels can be set-up
logical steady state analysis for a given set of inputs / fixed states:
useful for studying input-output behavior and signal processing
computation of (logical) minimal intervention sets (sets of knockouts/knock-ins) repressing or provoking a certain behavior or function
of the network
automated conversion of the logical model into an interaction graph
graphical display of the interaction matrix
Clipboard function; enables also arithmetic combinations ('+','-','\','*') of
different reaction or species (state) values for comparison of different
scenarios
Network composer: editing the network structure and properties of
network elements
Saving and printing of network maps and/or the values of (computed or
pre-defined) scenarios
Export of the network (interaction matrix)
Zoom tool (for zooming in and out in large maps)
Others
Fig. 1: Network composer in CellNetAnalyzer (here for a stoichiometric network).
Fig. 2: Input mask for defining a new network element of type reaction (here for a
stoichiometric network).
Fig. 3: Interactive network map of a stoichiometric (metabolic) network. The menu is
installed behind item "CellNetAnalyzer". The different coloroation of the text boxes
illustrates a flux scenario: green=defined rates, blue=calculated rates, gray=noncalculable rates ('###').
Fig. 4 Network map of a signaling network (simple model of T-cell activation). The blue
text boxes indicate a signaling path.
Publications on CellNetAnalyzer
Klamt S, Saez-Rodriguez J and Gilles ED. 2007. Structural and functional
analysis of cellular networks with CellNetAnalyzer. BMC Systems Biology,
1:2. <freeley available at BMC Systems Biology>
Klamt S, Saez-Rodriguez J, Lindquits J, Simeoni L and Gilles E.D. 2006. A
methodology for the structural and functional analysis of signaling and
regulatory networks. BMC Bioinformatics, 7:56. <freely available at BMC
Bioinformatics>
Klamt S, Gagneur J and von Kamp A. 2005. Algorithmic approaches for
computing elementary modes in large biochemical reaction networks. IEE
Proceedings Systems Biology, 152(4), 249-255.
Klamt S, Stelling J, Ginkel M and Gilles ED. 2003. FluxAnalyzer: exploring
structure, pathways, and flux distributions in metabolic networks on
interactive flux maps. Bioinformatics 19(2): 261-269.
Price list for CellNetAnalyzer
ACADEMIC USE (1) INDUSTRY
EUR (2)
EUR (2)
Demo version
free
free
Single user (*)
free
2.500,--
Site license / campus license (**):
•basic fee
•each user
-
2.500,-400,--
Single user + source code (***)
2.000,--
4.000,--
Site license source code (****):
•basic fee
•each user
-
4.000,-600,--
Prices do not include value added tax (VAT).
(1) Academic use: free academic license.
Here you can download CellNetAnalyzer for academic use.
(2) US-prices: Payments in US $ are welcome and will be based on the actual
exchange rate EUR / US $. Please ask the contact person for further details.
(*) includes executable software and a manual in PDF format, to be used on
one PC only, copies for backup purposes only
(**) includes executable software and a manual in PDF format, to be used on
the limited number of PC only, copies for backup purposes only
(***) includes executable software, the source code and a manual in PDF
format, to be used on one PC only, copies for backup purposes only
(****) includes executable software, the source code and a manual in PDF
format, to be used on the limited number of PC only, copies for backup
purposes only
The purchase comprises the actual version and the next update, e.g. purchaser
of version 6.0 receives 6.1 free of charge.
Academic institutions are universities, non-profit research laboratories, and
schools.