BACKGROUND: Stoichiometric models provide a structural framework for analyzing
steady-state cellular behavior. Models are developed either through augmentations
of existing models or more recently through automatic reconstruction tools. There
is currently no standardized practice or method for validating the properties of
a model before placing it in the public domain. Considerable effort is often
required to understand a model's inconsistencies before its reuse within new
research efforts. RESULTS: We present a review of common issues in stoichiometric
models typically uncovered during pathway analysis and constraint-based
optimization, and we detail succinct and efficient ways to find them. We present
MC3, Model and Constraint Consistency Checker, a computational tool that can be
used for two purposes: (a) identifying potential connectivity and topological
issues for a given stoichiometric matrix, S, and (b) flagging issues that arise
during constraint-based optimization. The MC3 tool includes three distinct
checking components. The first examines the results of computing the basis for
the null space for Sv = 0; the second uses connectivity analysis; and the third
utilizes Flux Variability Analysis. MC3 takes as input a stoichiometric matrix
and flux constraints, and generates a report summarizing issues. CONCLUSIONS: We
report the results of applying MC3 to published models for several systems
including Escherichia coli, an adipocyte cell, a Chinese Hamster Ovary cell, and
Leishmania major. Several issues with no prior documentation are identified. MC3
provides a standalone MATLAB-based comprehensive tool for model validation, a
task currently performed either ad hoc or implemented in part within other
computational tools.

MC3: a steady-state model and constraint consistency checker for biochemical networks.

MC3 is a tool for identifying connectivity, topological problems in stoichiometric matrices, and issues that occur in constraint-based optimization.

MC3

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