JigCell

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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 JigCell Model 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