Networks as a Privileged Way to Develop Mesoscopic Level Approaches in Systems Biology
Abstract
:1. Introduction
2. Microscopic Complexity Generates Macroscopic Simplicity
- (1)
- Human DNA molecule is a giant polymer approximately two meters long confined into a space of the scale of microns [5]. This implies the logical information stored in the DNA sequence is not freely accessible like in the RAM of a computer or in an abstract Turing machine. The most crucial step allowing a specific transcription pattern of the stored information (i.e., the correct genes at the correct expression level) is the unfolding of finely selected patches of the polymer correspondent to the genes of interest. Excluding the presence of any Maxwell’s demon, we must imagine the presence of relatively few “allowed configurations” of the DNA molecule exposing the “gene patterns” correspondent to different phenotypic states [6].This state of affairs has two immediate consequences: (a) regulation does not happen only on a gene-by-gene basis but in terms of “global modes” spanning the entire genome and (b) only a discrete (and relatively small) number of gene expression patterns do exist.The eventual local fine-tuning exerted on a gene-by-gene scale can be superimposed to the global “genome scale” regulation but explains a comparatively minor effect [7].
- (2)
- Tissues are populations made up of billions of cells that must work in a highly coordinated way (e.g., think of the necessity for cardiac muscle cells to oscillate in synchrony in order to obtain a normal heartbeat). This coordination implies the specific folding/refolding of chromosomes described in the previous point, must span the entire tissue, thus implying the necessity of a “communication system” unifying the entire tissue. This coordination was demonstrated to happen even in the very artificial situation of cells cultured on a Petri dish that in turn display very clear “gene expression waves” indicating a highly coordinated expression pattern spanning billions of cells. The existence of a cytoskeleton network creating a continuous communication system traversing different cells and entering the nuclei, received many experimental proofs [8,9], even if we are still very far to clarify the biophysical mechanisms of the information transmission along this network.
- (3)
- Basic physical chemistry tells us that an interaction involving the ordered encounters of three particles is practically impossible to achieve in a purely diffusive regime in solution. Ordinary metabolic processes like the biosynthesis of lipids [10] involve a dozen of ordered hits: this means we are forced to consider metabolism as a phenomenon occurring inside a structured solid phase. The presence of such ordered phase spanning supra-molecular scales is evident considering the dramatic effects exerted by lack of gravity in cells grown in the space shuttle [11]: thousands of genes appear to be dis-regulated. If we consider gravity has a null effect on the molecular scale, the huge biological consequences of the lack of gravity imply a top-down causation in which the maintaining of a supra-molecular order encompassing huge populations of cells comes before the molecular scale events and not the other way around as normally assumed by molecular biologists [12].
3. Networks are the Most Effective Paradigm to Look for Mesoscopic Organization Laws
4. Conclusions
Acknowledgments
Conflicts of Interest
References
- Roden, J.C.; King, B.W.; Trout, D.; Mortazavi, A.; Wold, B.J.; Hart, C.E. Mining gene expression data by interpreting principal components. BMC Bioinform. 2006, 7. [Google Scholar] [CrossRef]
- Sharov, A.A.; Dudekula, D.B.; Ko, M.S.H. A web-based tool for principal component and significance analysis of microarray data. Bioinformatics 2005, 21, 2548–2549. [Google Scholar] [CrossRef]
- Kitano, H. Systems biology: A brief overview. Science 2002, 295, 1662–1664. [Google Scholar] [CrossRef]
- Huang, S. Back to the biology in systems biology: What can we learn from biomolecular networks? Briefings Funct. Genom. Proteom. 2004, 2, 279–297. [Google Scholar] [CrossRef]
- Yoshikawa, K.; Takahashi, M.; Vasilevskaya, V.V.; Khokhlov, A.R. Large discrete transition in a single DNA molecule appears continuous in the ensemble. Phys. Rev. Lett. 1996, 76, 3029–3034. [Google Scholar] [CrossRef]
- Giuliani, A. Collective motions and specific effectors: A statistical mechanics perspective on biological regulation. BMC Genomics 2010, 11. [Google Scholar] [CrossRef]
- Tsuchiya, M.; Selvarajoo, K.; Piras, B.; Tomita, M.; Giuliani, A. Local and Global responses in complex gene regulation networks. Phys. A 2009, 388, 1738–1746. [Google Scholar] [CrossRef]
- Huber, F.; Schnauss, J.; Ronicke, S.; Rauch, P.; Müller, K.; Fütterer, C.; Käs, J. Emergent complexity of the cytoskeleton: from single filaments to tissue. Adv. Phys. 2013, 62, 1–112. [Google Scholar] [CrossRef]
- Butcher, D.T.; Alliston, T.; Weaver, V.M. A tense situation: Forcing tumor progression. Nat. Rev. Canc. 2009, 9, 108–121. [Google Scholar] [CrossRef]
- Ohlrogge, J.; Browse, J. Lipid biosynthesis. Plant Cell 1995, 7, 957–970. [Google Scholar] [CrossRef]
- Hammond, T.G.; Benes, E.; O’Reilly, K.C.; Wolf, D.A.; Linnehan, R.M.; Taher, A.; Kaysen, J.H.; Allen, P.L.; Goodwin, T.J. Mechanical culture conditions effect gene expression: Gravity-induced changes on the space shuttle. Physiol. Genom. 2000, 3, 163–173. [Google Scholar]
- D’Anselmi, F.; Valerio, M.C.; Cucina, A.; Galli, L.; Proietti, S.; Dinicola, S.; Pasqualato, A.; Manetti, C.; Ricci, G.; Giuliani, A.; Bizzarri, M. Metabolism and cell shape in cancer: A fractal analysis. Int. J. Biochem. Cell. Biol. 2011, 43, 1052–1058. [Google Scholar] [CrossRef]
- Tompa, P.; Rose, G.D. The Levinthal paradox of the interactome. Protein Sci. 2011, 20, 2074–2079. [Google Scholar] [CrossRef]
- Martindale, M.Q.; Lee, P.N. The development of form: Causes and consequences of developmental reprogramming associated with rapid body plan evolution in the bilaterian radiation. Biol. Theory 2013, 8, 253–264. [Google Scholar] [CrossRef]
- Denton, M.; Marshall, C. Laws of form revisited. Nature 2001, 410. [Google Scholar] [CrossRef]
- Von Dassow, G.; Meir, G.; Munro, E.M.; Garret, M.O. The segment polarity network is a robust developmental module. Nature 2000, 406, 188–192. [Google Scholar]
- Welch, G.R.; Keleti, T. On the “cytosociology” of enzyme action in vivo: A novel thermodynamic correlate of biological evolution. J. Theor. Biol. 1981, 93, 701–735. [Google Scholar] [CrossRef]
- Giuliani, A.; Filippi, S.; Bertolaso, M. Why network approach can promote a new way of thinking in biology. Front. Genet. 2014, 5, 1–4. [Google Scholar]
- Emmert-Sreib, F.; Dehmer, M. Networks for systems biology: Conceptual connection of data and function. IET Syst. Biol. 2011, 5, 185–207. [Google Scholar] [CrossRef]
- Di Paola, L.; De Ruvo, M.; Paci, P.; Santoni, D.; Giuliani, A. Protein contact networks: An emerging paradigm in chemistry. Chem. Rev. 2013, 113, 1598–1613. [Google Scholar] [CrossRef]
- Tasdighian, S.; Di Paola, L.; De Ruvo, M.; Paci, P.; Santoni, D.; Palumbo, P.; Mei, G.; Di Venere, A.; Giuliani, A. Modules identification in protein structures: The topological and geometrical solution. J. Chem. Inf. Model. 2014, 54, 159–168. [Google Scholar] [CrossRef]
- Censi, F.; Giuliani, A.; Bartolini, P.; Calcagnini, G. Multiscale graph theoretical approach to gene regulation networks: A case study in atrial fibrillation. IEEE Trans. Biomed. Eng. 2011, 99, 1–5. [Google Scholar]
- Palumbo, M.C.; Colosimo, A.; Giuliani, A.; Farina, L. Essentiality is an emergent property of metabolic network wiring. FEBS Lett. 2007, 581, 2485–2489. [Google Scholar] [CrossRef]
- Dehmer, M.; Mueller, L.A.J.; Emmert-Streib, F. Quantitative network measures as biomarkers for classifying prostate cancer disease states: A systems approach to diagnostic biomarkers. PLoS ONE 2013, 8. [Google Scholar] [CrossRef]
- Csermely, P.; Korcsmáros, T.; Kiss, H.J.; London, G.; Nussinov, R. Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review. Pharmacol. Therapeut. 2013, 138, 333–408. [Google Scholar] [CrossRef]
- Laughlin, R.B.; Pines, D.; Schmalian, J.; Stojković, B.P.; Wolynes, P. The middle way. Proc Natl. Acad. Sci. USA 2000, 97, 32–37. [Google Scholar] [CrossRef]
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Giuliani, A. Networks as a Privileged Way to Develop Mesoscopic Level Approaches in Systems Biology. Systems 2014, 2, 237-242. https://doi.org/10.3390/systems2020237
Giuliani A. Networks as a Privileged Way to Develop Mesoscopic Level Approaches in Systems Biology. Systems. 2014; 2(2):237-242. https://doi.org/10.3390/systems2020237
Chicago/Turabian StyleGiuliani, Alessandro. 2014. "Networks as a Privileged Way to Develop Mesoscopic Level Approaches in Systems Biology" Systems 2, no. 2: 237-242. https://doi.org/10.3390/systems2020237