## CADLIVE

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

** Abstract** The CADLIVE (Computer-Aided Design of LIVing systEms)
System is a comprehensive group of computational tools that analyzes
and rationally designs large-scale 'biochemical networks' at the
molecular interaction level.

It provides a rule-based automatic way to convert 'biochemical network' maps into dynamic models, which enables simulating their dynamics without going through all of the reactions down to the details of exact kinetic parameters.

The simulator supports the biochemical reaction maps that are generated by a GUI editor.

To directly link biochemical network maps to the dynamic simulation, the manufacturer has created the strategy of three layers and two stages with efficient conversion rules in an Extensible Markup Language (XML) representation.

This strategy divides a molecular network into three layers, i.e., gene, protein, and metabolic layers, and partitions the conversion process into two stages.

Once a biochemical map is provided, CADLIVE automatically builds a mathematical model, thereby facilitating one to simulate and analyze it.

CADLIVE consists of multiple software modules/programs which include the CADLIVE GUI Network Constructor, the Pathway Search Program for Virtual Knockout Mutants, the CADLIVE Grid Layout Program, the CADLIVE Dynamic Simulator, and CADLIVE Metabolic Engineering Tools.

1) The CADLIVE Network Constructor enables one to construct large- scale biological networks (metabolic and gene regulatory networks) using a GUI (Graphic User Interface) and saving them as regulator reaction equations in a database in a format compatible to the Dynamic simulator.

2) The Pathway Search Program for Virtual Knockout Mutants explores all possible pathways between two species, and can be applied to knockout mutants.

The manufacturers developed the pathway search module for virtual knockout mutants as a built-in application of CADLIVE.

This module analyzes gene function in the same way as molecular genetics, which simulates a change in mutant phenotypes or confirms the validity of the network map.

3) The CADLIVE Grid Layout Program automatically lays out 'biochemical networks' on a two-dimensional square grid. A grid layout is a special kind of graph layout, where all graph nodes are placed on a 2-dimensional square grid.

The manufacturer has developed an algorithm to compute grid layouts for graphs.

In their approach, a graph is modeled as a system of interacting particles (nodes) on a given grid. The nodes interact according to a 'cost function' which is designed based on the topological structure of the network.

In such a system, closely related nodes attract each other, and remotely related nodes repulse each other.

The manufacturer expresses their network layout method as an 'optimization algorithm' which aims at finding optimized solutions of a certain ‘objective cost’ that is a function of the layouts of the input network.

The network is modeled as a system of interacting particles which are placed on a 2-dimensional square grid. The network is confined within an area L.

The particles (nodes) interact according to a predefined energy function based on the network topological structure. A configuration of the particles represents a layout of the network, in which all edges are simple straight lines.

The energy of a configuration is the 'cost score' of the corresponding layout. A stable configuration has low energy; equivalence, and an acceptable layout has a low cost score.

4) The CADLIVE Dynamic Simulator automatically converts biochemical network maps into dynamic mathematical models and simulates their dynamics.

The Dynamic Simulator consists of:

- a) Editors that describe regulator-reaction models;
- b) The parser (parsedae module) that converts the regulator-reaction equations into a mathematical model -
- (Parsedae module - Based on three layers and two stages, the parsedae module parses and converts the “sanac” (Synthesis and Analysis of Networks Architecture in Computer) file for regulator-reaction equations with various elements and attributes into mathematical models (a checkdae file) according to selected mathematical formulas);
- c) The converter (checkdae module) that changes the mathematical model into a C programming language subroutine-
- (Checkdae module - The checkdae module converts a mathematical model, which was written in the checkdae file, into the user functions that will be complied by the C language to link to simulation libraries and the parameter setting file, where one sets the initial concentrations of the molecules, the kinetic parameters, and the parameters for controlling the simulation process);
- d) The simulator engine (solver) -
- (Solver - Two distinct types of simulation can be carried out as follows: 1) time course simulation, where the values of variables are determined as a time series; 2) steady-state analysis, where the values of variables are determined for a state in which the metabolite concentration does Not change);
- e) The optimizer for estimating the values of biochemical parameters that are used to reproduce experimental behaviors -
- (Optimizer - CADLIVE implements a search by Genetic Algorithms (GAs), where a fitness function is defined to characterize how correctly the estimated values of the kinetic parameters explain experimental data);
- f) The analyzer that carries out sensitivity/stability analysis and S-system analysis;
- g) The visualizer that draws simulated results; and h) the database for storing mathematical models.

5) The Metabolic Engineering Tools are developed as elementary mode based algorithms.

The manufacturer offers two (2) new tools for elementary mode analysis in metabolic engineering --

- a) Maximum Entropy Principle for optimization of elementary mode coefficient.
- b) Genetic Modification Flux (GMF) for prediction of a flux distribution in various types of genetic mutants - GMF: modified Control Effective Flux & Enzyme Control Flux.

*System Requirements*

Contact manufacturer.

*Manufacturer*

- Kurata Laboratory
- Department of Bioscience and Bioinformatics
- Kyushu Institue of Technology (KIT)
- 680-4 Kawazu, Iizuka, Fukuoka, 820-8502
- JAPAN
- Tel: F0948-29-7828
- Fax: F0948-29-7828

** Manufacturer Web Site**
CADLIVE

** Price** Contact manufacturer.

** G6G Abstract Number** 20469

** G6G Manufacturer Number** 104094