Schematic Representation and Database Population Strategies for Sigmoid, a Biochemical Network Modeling System

Progress in systems biology critically depends on developing scalable informatics tools to model and visualize complex biological systems. Flexibly storing information about these systems and their models for subsequent retrieval and analysis is also a key concern. The focus of the research reported here has been the development of the Sigmoid project and associated pathway models. The Sigmoid project (www.sigmoid.org) provides biologists with a database, modeling and simulation platform for signal transduction, metabolic and biosynthetic pathways. Sigmoid has been implemented as a three-tier architecture, consisting of client, web service, and back end simulator/database. Sigmoid provides a front end to the xCellerator / kMech / Mathematica simulation platform and enables mathematical simulations of biochemical networks [Shapiro 2007] [Yang et al. 2005b]. A visualization and simulation platform such as this allows wet bench biologists to make targeted decisions about their experimental designs and save on unnecessary expenditures of wet bench resources. Many published models are currently available and functional within the Sigmoid framework. The models focus on virtual representation of intracellular pathways that include examples in signaling, metabolism, the cell cycle, and gene regulation.;To facilitate the modeling of organelle, multi-cellular and developmental models within the Sigmoid framework, a back-end representation for multi-compartmental modeling was added to the Sigmoid schema. Although the Schema representation for this is more comprehensive, a first step compatibility with the xCellerator "Cellzilla" utility was implemented. A model of Wuschel expression [Jonsson 2005] in the Arabidopsis thaliana shoot apical meristem has been completed with the Sigmoid representation.;kMech [Yang 2005] is an enzyme mechanism modeling tool designed for the mathematical modeling of enzymes. It comprises a collection of single and multiple substrate enzyme reactions. Over the years the library of requested enzymatic reactions implemented in the kMech utility and correspondingly in Sigmoid has grown substantially. A new generalized version of the kMech enzyme mechanism modeling tool has been developed. With this utility, SigMech, the approximately 35 existing enzyme mechanism models expressed explicitly in the kMech/Sigmoid platform can be expressed implicitly by a single parameterized input notation. Subsequent sub-reactions can be generated procedurally, and any potential "new" kMech enzyme mechanisms that fall within the pattern abstracted from previous motifs need not be created explicitly.