Networks of Networks: An Essay on Multi-Level Biological Organization

Abstract

The multi-level organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism, while in the same time each protein (a single node of such interaction network) is itself a network of interacting amino-acid residues allowing coordinated motion of the macromolecule and systemic effect as allosteric behavior. Similar pictures can be drawn for structure and function of cells, organs, tissues, and ecological systems. The majority of biologists are used to think that causally relevant events originate from the lower level (the molecular one) in the form of perturbations, that “climb up” the hierarchy reaching the ultimate layer of macroscopic behavior (e.g., causing a specific disease). Such causative model, stemming from the usual genotype-phenotype distinction, is not the only one. As a matter of fact, one can observe top-down, bottom-up, as well as middle-out perturbation/control trajectories. The recent complex network studies allow to go further the pure qualitative observation of the existence of both non-linear and non-bottom-up processes and to uncover the deep nature of multi-level organization. Here, taking as paradigm protein structural and interaction networks, we review some of the most relevant results dealing with between networks communication shedding light on the basic principles of complex system control and dynamics and offering a more realistic frame of causation in biology.

Intrinsically Disordered Proteins: Critical Components of the Wetware

“…As self-organizing systems, scale-free networks are composed of self-repeating patterns (fractals) across diverse length scales . Curiously, the same principles are also applicable to individual proteins because the spatiotemporal structural organization can be envisaged as an intraprotein network, wherein the individual amino acids participate in interactions that are transient or stable . In fact, it was recently shown that a protein molecule may be visualized as a complex system existing as a dynamic, multilevel network of networks analogous to a nesting doll (Matryoshka).…”

Characterization of exogenous αSN response genes and their relation to Parkinson’s disease using network analyses

“…Subsequently, we examined the topological features of the PD-EASR network. This revealed that the PD-EASR network is a scale-free network, which is a common characteristic of biological networks (Uversky and Giuliani, 2021). Also, to fully understand the functional links between PD-related genes and EASR genes, we performed enrichment analysis for the core PD-EASR network, representing its function in neuron death (GO:0070997).…”

Replacement, reduction, refinement: 3 days for 3Rs

“…Grimace scales have been developed for a range of different species including rats, rabbits, and horses and can provide a useful and rapid method both for pain detection and in determining whether an-Alessandro Giuliani (Istituto Superiore di Sanità -ISS, Italy) introduced the concept of Reduction from a wide theoretical perspective. He argued that the behavior of biological systems emerges from the correlation of different players at all biological and organization levels from molecules to ecosystems (Uversky and Giuliani, 2021). This implies that there is no single privileged level of explanation (prediction) for biologically relevant endpoints.…”