Complex Systems Biology of Networks: The Riddle and the Challenge - Systems Biology of Metabolic and Signaling Networks - page 29

2.4 Concluding Remarks

The fundamental complexity and uniqueness of living systems resides in their
capacity for self-making and -repairing (Luisi 2006 ; Varela et al. 1974 ). This
distinctive trait is possible to be accomplished through closed loop topologies of
nonlinearly interrelated processes operating in thermodynamically open systems
thereby subjected to continuous energy dissipation and exchange of matter, e.g.,
substrates, and gases.
Another consequence of the self-making ability of living systems is that some
network components (nodes, e.g., metabolites like AMP or TFs such as NF

B)
can be both cause and effect at the same time (or output and input) for the
same network, i.e., mass-energy and information, respectively, in these examples.
A plethora of computational and experimental network-based methods are being
developed and applied to different biological systems including complex diseases
(Cho et al. 2012 ; Kholodenko et al. 2012 ; Neph et al. 2012 ; Przytycka and Cho
2012 ). It is worth remarking that the data and meaningful information that these
approaches can provide are just the starting point for testable hypotheses.
The dynamic diversity arising from the interactions between spatially distributed
mass-energy/information/signaling networks organized in circularly connected
topologies has potentially explosive combinatorial possibilities. The modulation
exerted by signaling networks on the spatio-temporal unfolding of mass-energy/
information networks, together with the countless available dynamic paths
emerging from these interactions, generates both the uniqueness and diversity of
living creatures. Interestingly, recent findings have highlighted the marked cell type
specificity of human transcriptional regulatory networks, with only ~5 % of overlap
across 41 tested cell types, thereby underscoring the high regulatory diversity
within humans (Neph et al. 2012 ).

κ

Acknowledgments This work was performed with the financial support of R01-HL091923
from NIH.

References

Aggarwal NT, Makielski JC (2013) Redox control of cardiac excitability. Antioxid Redox Signal
18:432-68
Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10
(Suppl):S18-25
Aon MA, Cortassa S (1997) Dynamic biological organization. Fundamentals as applied to cellular
systems. Chapman & Hall, London
Aon MA, Cortassa S (2009) Chaotic dynamics, noise and fractal space in biochemistry. In: Meyers
R (ed) Encyclopedia of complexity and systems science. Springer, New York
Aon MA, Cortassa S (2012) Mitochondrial network energetics in the heart. Wiley Interdiscip Rev
Syst Biol Med 4:599-613