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first three of those we have described as the roots of systems biology, the latter
two as its branches. So we have to look how each particular root feeds into the
branches.
It seems obvious that pathway modeling hands down its bottom-up way of
modeling and reliance on detailed kinetic data to the bottom-up branch of sys-
tems biology. Both approaches build models in a way that may be characterized
as functional composition from detailed kinetic and some structural data. We
see richer structural data, i.e., incorporation of more components into the model,
on the side of systems biology. To the extent that it is achieved by the applica-
tion of high-throughput methods, this gain in richness of structural data can be
seen as an influence of 'omics'. We therefore regard 'omics' as another, though
less important, root of bottom-up systems biology (see Fig. 1). The other main
difference between both approaches is the way the functionality of the systems
components is dealt with. Pathway modeling sometimes assigns regulatory func-
tions to particular components of a pathway, referring to a rate-limiting step at
which the flux through the pathway is controlled. This notion was already given
up in metabolic control analysis (Kacser & Burns, 1973; Heinrich & Rapoport,
Pathway modeling
Bottom-up approach
(functional composition)
Kinetic data (components)
Some structural data
Localized functionality
Bottom-up systems biology
Bottom-up approach
(functional composition)
Kinetic data (components)
Richer structural data (bottom level)
Distributed functionality
Omics
Bottom level only
Poor kinetic data
Rich structural data
Some dynamics,
no function
Top-down systems biology
Top-down approach
(decomposition into modules)
Kinetic data (systems level)
Rich structural data (top level!)
Distributed functions/dynamic roles
Biological cybernetics
Top-down approach
(functional decomposition)
Kinetic data (input-output)
Poor in structural data
Localized functionality assumed
Figure 1
The structure of the field of systems biology.
Thickness of arrows indicates roughly the strength of the links between the root disciplines (left)
and the branches of systems biology (right). The vertical arrows indicate interchange between
pathway modeling and biological cybernetics, and between both branches of systems biology,
respectively. The dotted demarcation line between the two branches of systems biology shall
indicate that both kinds of modeling are often combined within one model.
