Otherwise, Theoretical Systems Biology, according to which
both theoretical and methodological approaches in biological
research must be radically changed. That statement has recently
been underscored [3]. Theoretical Systems Biology recognizes that
complex physiological and adaptive phenomena take place at
biological levels of organization higher than the subcellular
one [3].
We define systems biology as the study of complex interactions
in biological systems and the emergent properties that arise from
such interactions. In the field of cancer, systems biology aims at
developing an increasingly holistic view of cancer development and
progression [4].
A system-level understanding of a biological system can be
derived from insight into four key properties [5]:- System structures. These include the network of gene interac-
tions and biochemical pathways, as well as the mechanisms by
which such interactions modulate the physical properties of
intracellular and multicellular structures. - System dynamics. How a system behaves over time under
various conditions can be understood through metabolic anal-
ysis, sensitivity analysis, dynamic analysis methods such as phase
portrait and bifurcation analysis, and by identifying essential
mechanisms underlying specific behaviors. Bifurcation analysis
traces time-varying change(s) in the state of the system in a
multidimensional space where each dimension represents a
particular concentration of the biochemical factor involved. - The control method. Mechanisms that systematically control
the state of the cell can be modulated to minimize malfunctions
and provide potential therapeutic targets for treatment of
disease. - The design method. Strategies to modify and construct
biological systems having desired properties can be devised
based on definite design principles and simulations, instead of
blind trial-and-error. Progress in any of the above areas is
reviewed at [5].
We are therefore facing a significant intellectual challenge: how
to include chaotic and nonlinear, unpredictable processes into our
comprehension of Biology. This task will likely improve our under-
standing of complexity of the real world, no longer confined to
simplified and idealized phenomena. Systems Biology entails inves-
tigating phenomena in terms of how the objects are related, rather
than what their compositions are [3].
It has been emphasized by von Bertalanffy that, “according to
definition, the second law of thermodynamics applies only to closed
systems, it does not define the steady state.” The extension and
generalization of thermodynamical theory has been carried throughParameters Estimation in Phase-Space Landscape Reconstruction of Cell Fate... 127