Improving the Development Process for Eukaryotic Cell Cycle Models with a Modeling Support Environment

Abstract

Theoretical molecular biologists attempt to describe cellular processes and regulatory networks with continuous and discrete mathematical models. Previous practice has been to develop models largely by hand and then to validate them primarily by comparing time-series plots versus the observed experimental results. The authors report their experiences in designing and building a modeling support environment for cell cycle models. They describe improvements to the development process for molecular network models by (a) identifying the key elements of the existing modeling process, (b) incorporating simulation methodology into a revised modeling process, and (c) building and testing software that supports the revised modeling process.

Mathematical modeling as a tool for investigating cell cycle control networks

“…JigCell is a modeling environment for Windows being developed as part of the larger DARPA BioSPICE effort (33,34). Although still a work-in-progress, JigCell includes a convenient spreadsheet-style Model Builder, a Run Manager for organizing related parameter sets and running multiple simulations (35), a Comparator for comparing simulations to experimental data (36), and a Parameter Estimator (21,37).…”

“…Although still a work-in-progress, JigCell includes a convenient spreadsheet-style Model Builder, a Run Manager for organizing related parameter sets and running multiple simulations (35), a Comparator for comparing simulations to experimental data (36), and a Parameter Estimator (21,37). Although JigCell is suited for modeling any biochemical network, it was developed with a particular emphasis on modeling the cell cycle.…”

Computational steering in the problem solving environment WBCSim

“…It provides a Web based interface for potential watershed managers and other users to explore meaningful alternative land development and management scenarios and view their hydrological, ecological, and economic impacts. The JigCell model builder [2], [39], [1], [40], allows users to define chemical kinetic models as a set of reaction equations using a spreadsheet (an example of direct entry of equations) and outputs model definitions in the Systems Biology Markup Language. This spreadsheet paradigm demonstrates its effectiveness in reducing the number of errors made by systems biology modelers when compared to hand conversion of a metabolic pathway wiring diagram to differential equations.…”

Challenges for Modeling and Simulation Methods in Systems Biology

“…Our tools include the JigCell Model Builder (Vass et al 2006) for creating and editing models, the JigCell Run Manager (Allen et al 2003) for organizing the various mutants, and the JigCell Comparator (Allen et al 2003) for analyzing the goodness of fit between the experimental data and the simulation outputs. Such tools allow for the automation of model validation procedures.…”