Genome-Scale Models of Metabolic and Regulatory Networks - Systems Biology: Networks, Models, and Applications - page 230

Genome-Scale Models of Metabolic
and Regulatory Networks
Markus J. Herrgård & Bernhard Ø. Palsson
Mathematical models of biochemical networks have been built
from the very early days of biochemistry and molecular biology [1].
However, these models have been focused on small subsystems
that are thought to represent an independent module in the whole
biochemical network of the cell. This subsystem-based approach was
necessitated by the limited information available on the entire set of
proteins that are present in a particular cell. The availability of genome
sequences has allowed the development of systematic approaches
to establish functions for unannotated genes and regulatory regions
[2-5]. The resulting list of well-characterized coding and regulatory
regions in a genome has further enabled the reconstruction of the
structure of metabolic and regulatory networks at the genome scale.
In this chapter we describe the process of reconstructing genome-
scale metabolic and regulatory networks, provide an overview of
methods that have been developed to study these reconstructions in
silico, and describe applications of existing network reconstructions.
Network-level steady-state assumption has been used to derive a number
of powerful mathematical analysis tools that can be used to elucidate
network function in silico. These tools are based on imposing a succes-
sion of constraints on the cellular function giving rise to the term
“constraint-based analysis” to describe the overall framework [6-8].
While the basic chemistry underlying metabolic and regulatory
networks is the same, the different nature of the molecular compo-
nents makes the reconstruction and analysis of these two network
types quite different in practice. We will first discuss the fairly mature
field of genome-scale metabolic network reconstruction and analysis.
Since metabolic network reconstruction can be done routinely based
on database and literature information, the focus of this section is
on describing existing genome-scale models and their uses in biological
discovery. The other major aim of the metabolic network section is to
give relevant background on the in silico constraint-based analysis
methods that can be used to study the properties of metabolic network
reconstructions and make experimentally testable predictions using
network models. In the second part of this chapter the reconstruction
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