JigCell

1. JigCell Nicholas A. Allen*, Kathy C. Chen**, Emery D. Conrad**, Ranjit Randhawa*, Clifford A. Shaffer*, John J. Tyson**, Layne T. Watson* and Jason W. Zwolak* Synopsis Our goal is to produce an integrated suite of tools for pathway modeling. JigCell includes: a Model Builder for describing a set of pathways, a Run Manager for recording mutant and parameter sets, a Comparator for making quantitative evaluation of the model against the known experimental evidence, a Parameter Estimator Toolkit (PET) and a numerical bifurcation analysis package (Oscill8). XPP is included as a simulator. Standards JigCell supports the System Biology Markup Language (SBML) standard for models and the developing basal, run file standards and the BioSPICE timeseries format. These standards ensure interoperability between JigCell and other tools for computational biology. Figure: Oscill8 The Modeling Process Our efforts are also directed to improving and automating the modeling process itself. We have observed the iterative process used by modelers and created a formal basis for its description. Better understanding of the modeling process improved our software development planning and helps us identify where computer assistance is needed. Automated model evaluation has greatly reduced the time required to develop new models. Tools The JigCellModel Builder (JCMB) uses a spreadsheet interface and aides the modeler in defining a system to be modeled using SBML. In addition to allowing the modeler to define chemical species, equations, and relationships, JCMB also provides the ability to define events that occur when a user-defined condition is met. These models can be used in conjunction with the other JigCell tools to simulate the behavior of the model, and to evaluate the ability of the model to match the phenomena the model is meant to represent The Run Manager allows a user to define and manage a collection of specifications for simulation runs using a spreadsheet interface. Each row of the spreadsheet describes the information necessary for a single simulation run, and typically represents the information that distinguishes a particular mutation from the reference “wild type.” The Comparator allows the user to perform a quantitative analysis on a collection of data sets. Users specify experimental data; a transformation to rectify the differences in format between experimental data and simulation output; and an objective function to score the distance between transformed simulation output and the reference experimental data. Various visualization techniques allow the user to quickly judge the quality of the match between experimental data and simulation output for complex models. PET (Parameter Estimation Tool) enables automated discovery of model parameter values by numerically minimizing the difference between model and experimental results. Using parameter estimation instead of hand-fitting the parameters eliminates one of the largest labor-intensive tasks. Oscill8 is a suite of tools for analyzing large systems of ODEs, particularly with respect to understanding how the high dimensional parameter space controls the dynamics of the system. Future software development will focus on adding new tools to the suite and tuning the existing tools based on feedback from modelers. We hope to support domain experts in biology and related fields without requiring a background in formal modeling. Figures: (from top to bottom) Budding yeast model in the Model Builder, Run Manager and Comparator For More Information: http://jigcell.biol.vt.edu/ * Department of Computer Science, 660 McBryde Hall (0106) and ** Department of Biological Sciences, 2119 Derring Hall (0406) Virginia Tech, Blacksburg, VA 24061 Figure: Budding yeast model in PET