MOTIVATION: We introduce Pycellerator, a Python library for reading Cellerator arrow notation from standard text files, conversion to differential equations, generating stand-alone Python solvers, and optionally running and plotting the solutions. All of the original Cellerator arrows, which represent reactions ranging from mass action, Michales-Menten-Henri (MMH) and Gene-Regulation (GRN) to Monod-Wyman-Changeaux (MWC), user defined reactions and enzymatic expansions (KMech), were previously represented with the Mathematica extended character set. These are now typed as reaction-like commands in ASCII text files that are read by Pycellerator, which includes a Python command line interface (CLI), a Python application programming interface (API) and an iPython notebook interface. RESULTS: Cellerator reaction arrows are now input in text files. The arrows are parsed by Pycellerator and translated into differential equations in Python, and Python code is automatically generated to solve the system. Time courses are produced by executing the auto-generated Python code. Users have full freedom to modify the solver and utilize the complete set of standard Python tools. The new libraries are completely independent of the old Cellerator software and do not require Mathematica. AVAILABILITY AND IMPLEMENTATION: All software is available (GPL) from the github repository at https://github.com/biomathman/pycellerator/releases. Details, including installation instructions and a glossary of acronyms and terms, are given in the Supplementary information.

Abstract Motivation: As a first step toward the elucidation of the systems biology of complex biological systems, it was our goal to mathematically model common enzyme catalytic and regulatory mechanisms that repeatedly appear in biological processes such as signal transduction and metabolic pathways. Results: We describe kMech, a Cellerator language extension that describes a suite of enzyme mechanisms. Each enzyme mechanism is parsed by kMech into a set of fundamental association–dissociation reactions that are translated by Cellerator into ordinary differential equations that are numerically solved by Mathematica™. In addition, we present methods that use commonly available kinetic measurements to estimate rate constants required to solve these differential equations. Availability: A Mathematica™ executable kMech.m file is available at the University of California, Irvine, Institute for Genomics and Bioinformatics website, http://www.igb.uci.edu/servers/sb.html. Cellerator, free of charge to academic, US government, and other non-profit organizations, can be obtained at the Cellerator website, (http://www-aig.jpl.nasa.gov/public/mls/cellerator/feedback.html). Contact: Biology correspondence should be addressed to [email protected]. Computation correspondence should be addressed to [email protected]. Supplementary information: http://www.igb.uci.edu/servers/sb.html.

Abstract Summary: MathSBML is a Mathematica package designed for manipulating Systems Biology Markup Language (SBML) models. It converts SBML models into Mathematica data structures and provides a platform for manipulating and evaluating these models. Once a model is read by MathSBML, it is fully compatible with standard Mathematica functions such as NDSolve (a differential-algebraic equations solver). MathSBML also provides an application programming interface for viewing, manipulating, running numerical simulations; exporting SBML models; and converting SBML models in to other formats, such as XPP, HTML and FORTRAN. By accessing the full breadth of Mathematica functionality, MathSBML is fully extensible to SBML models of any size or complexity. Availability: Open Source (LGPL) at http://www.sbml.org and http://www.sf.net/projects/sbml. Supplementary information: Extensive online documentation is available at http://www.sbml.org/mathsbml.html. Additional examples are provided at http://www.sbml.org/software/mathsbml/bioinformatics-application-note

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Abstract Summary: Cellerator describes single and multi-cellular signal transduction networks (STN) with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation. Multi-compartment systems are represented as graphs with STNs embedded in each node. Interactions include mass-action, enzymatic, allosteric and connectionist models. Reactions are translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs. Cellerator simulations are fully extensible and portable to any operating system that supports Mathematica, and can be indefinitely nested within larger data structures to produce highly scaleable models. Availability: Cellerator can be licensed free of charge to noncommercial academic, U.S. government, and nonprofit users. Details and sample notebooks are available at http://www-aig.jpl.nasa.gov/public/mls/cellerator. Contact: [email protected] * To whom correspondence should be addressed.