Biology Reference
In-Depth Information
has an indirect influence on top-down systems biology, and biological cybernet-
ics accordingly has an indirect influence on bottom-up systems biology. 'Omics',
in contrast, is not strongly linked to the two other roots of systems biology.
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It
stands itself in the traditions of molecular biology and enzyme kinetics. How-
ever, since molecular biology is also an important source for pathway modeling
(which is clear in particular from early models: Krebs, Warburg), we do not
trace back the tradition of 'omics' to molecular biology as one discernable root
of systems biology (as, e.g., Westerhoff and Palsson (2004) do), but refer to
'early omic projects' as the onset of this root of systems biology.
Up to this point, we followed the habit of separating systems biological mod-
els into two classes that are clearly discernable by the 'direction' of modeling.
However, as we already noted, bottom-up and top-down approaches are often
combined. Palsson, for one, points out the need to combine bottom-up and top-
down strategies in the modeling of transcriptional regulatory networks (Palsson,
2006, p. 66) and some convergence is stated with respect to the two branches of
the field (Westerhoff & Palsson, 2004). The top-down approach tries to decom-
pose large networks into modules. These modules may be described separately
by smaller top-down models, but also by bottom-up models. This overcomes the
strict demarcation between both branches of the field, which is indicated by the
dashed line in Fig. 1. Systems biology, although certainly not a homogeneous
field, can be regarded as a unity if the aspect of the direction of modeling is
given less weight. A shared perspective can be found in regarding functionality
as distributed over the components of complex networks. Another commonality
of both branches of systems biology is the search for detailed models, though
the degree of detail aspired at by researchers is higher with respect to top-down
than with respect to bottom-up models. Most important in this respect might be
the attitude to model 'whole' systems in such a way as to describe networks
embracing entities that are in some sense 'wholes': cells, organs, organisms, etc.
8. EPISTEMOLOGICAL AND ONTOLOGICAL ISSUES
REGARDING TOP-DOWN SYSTEMS BIOLOGY
Up to now, we have dealt with systems biology from a reconstructive perspective
to analyze the structure of the merger of different roots into systems biology
and the changes in basic modeling strategies that took place. As we have seen,
systems biology of the bottom-up branch is very much in line with its predecessor
theories. The top-down branch, however, displays some drastic novelties in data
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There are, of course, other links that represent shared methods such as different kinds of radioactive marking
and diverse analytic techniques. We regard these as too general to be relevant to the structure of the field.
