Generalized network density matrices for analysis of multiscale functional diversity

The network density matrix formalism allows for describing the dynamics of information on top of complex structures and it has been successfully used to analyze from system's robustness to perturbations to coarse graining multilayer networks from characterizing emergent network states to performing multiscale analysis. However, this framework is usually limited to diffusion dynamics on undirected networks. Here, to overcome some limitations, we propose an approach to derive density matrices based on dynamical systems and information theory, that allows for encapsulating a much wider range of linear and non-linear dynamics and richer classes of structure, such as directed and signed ones. We use our framework to study the response to local stochastic perturbations of synthetic and empirical networks, including neural systems consisting of excitatory and inhibitory links and gene-regulatory interactions. Our findings demonstrate that topological complexity does not lead, necessarily, to functional diversity -- i.e., complex and heterogeneous response to stimuli or perturbations. Instead, functional diversity is a genuine emergent property which cannot be deduced from the knowledge of topological features such as heterogeneity, modularity, presence of asymmetries or dynamical properties of a system

Multiscale statistical physics of the pan-viral interactome unravels the systemic nature of SARS-CoV-2 infections

AbstractProtein–protein interaction networks have been used to investigate the influence of SARS-CoV-2 viral proteins on the function of human cells, laying out a deeper understanding of COVID–19 and providing ground for applications, such as drug repurposing. Characterizing molecular (dis)similarities between SARS-CoV-2 and other viral agents allows one to exploit existing information about the alteration of key biological processes due to known viruses for predicting the potential effects of this new virus. Here, we compare the novel coronavirus network against 92 known viruses, from the perspective of statistical physics and computational biology. We show that regulatory spreading patterns, physical features and enriched biological pathways in targeted proteins lead, overall, to meaningful clusters of viruses which, across scales, provide complementary perspectives to better characterize SARS-CoV-2 and its effects on humans. Our results indicate that the virus responsible for COVID–19 exhibits expected similarities, such as to Influenza A and Human Respiratory Syncytial viruses, and unexpected ones with different infection types and from distant viral families, like HIV1 and Human Herpes virus. Taken together, our findings indicate that COVID–19 is a systemic disease with potential effects on the function of multiple organs and human body sub-systems

Statistical physics of complex information dynamics

The constituents of a complex system exchange information to function properly. Their signalling dynamics often leads to the appearance of emergent phenomena, such as phase transitions and collective behaviors. While information exchange has been widely modeled by means of distinct spreading processes -- such as continuous-time diffusion, random walks, synchronization and consensus -- on top of complex networks, a unified and physically-grounded framework to study information dynamics and gain insights about the macroscopic effects of microscopic interactions, is still eluding us. In this article, we present this framework in terms of a statistical field theory of information dynamics, unifying a range of dynamical processes governing the evolution of information on top of static or time varying structures. We show that information operators form a meaningful statistical ensemble and their superposition defines a density matrix that can be used for the analysis of complex dynamics. As a direct application, we show that the von Neumann entropy of the ensemble can be a measure of the functional diversity of complex systems, defined in terms of the functional differentiation of higher-order interactions among their components. Our results suggest that modularity and hierarchy, two key features of empirical complex systems -- from the human brain to social and urban networks -- play a key role to guarantee functional diversity and, consequently, are favored.Comment: 7 pages, 3 figure

Multiscale Information Propagation in Emergent Functional Networks

Complex biological systems consist of large numbers of interconnected units, characterized by emergent properties such as collective computation. In spite of all the progress in the last decade, we still lack a deep understanding of how these properties arise from the coupling between the structure and dynamics. Here, we introduce the multiscale emergent functional state, which can be represented as a network where links encode the flow exchange between the nodes, calculated using diffusion processes on top of the network. We analyze the emergent functional state to study the distribution of the flow among components of 92 fungal networks, identifying their functional modules at different scales and, more importantly, demonstrating the importance of functional modules for the information content of networks, quantified in terms of network spectral entropy. Our results suggest that the topological complexity of fungal networks guarantees the existence of functional modules at different scales keeping the information entropy, and functional diversity, high

Diversity of information pathways drives scaling and sparsity in real-world networks

Empirical complex systems must differentially respond to external perturbations and, at the same time, internally distribute information to coordinate their components. While networked backbones help with the latter, they limit the components' individual degrees of freedom and reduce their collective dynamical range. Here, we show that real-world networks are formed to optimize the gain in information flow and loss in response diversity. Encoding network states as density matrices, we demonstrate that such a trade-off mathematically resembles the thermodynamic efficiency characterized by heat and work in physical systems. Our findings explain, analytically and numerically, the sparsity and the empirical scaling law observed in hundreds of real-world networks across multiple domains. We show, through numerical experiments in synthetic and biological networks, that ubiquitous topological features such as modularity and small-worldness emerge to optimize the above trade-off for middle- to large-scale information exchange between system's units. Our results highlight that the emergence of some of the most prevalent topological features of real-world networks have a thermodynamic origin

Multiscale statistical physics of the pan-viral interactome unravels the systemic nature of SARS-CoV-2 infections

Protein–protein interaction networks have been used to investigate the influence of SARS-CoV-2 viral proteins on the function of human cells, laying out a deeper understanding of COVID–19 and providing ground for applications, such as drug repurposing. Characterizing molecular (dis)similarities between SARS-CoV-2 and other viral agents allows one to exploit existing information about the alteration of key biological processes due to known viruses for predicting the potential effects of this new virus. Here, we compare the novel coronavirus network against 92 known viruses, from the perspective of statistical physics and computational biology. We show that regulatory spreading patterns, physical features and enriched biological pathways in targeted proteins lead, overall, to meaningful clusters of viruses which, across scales, provide complementary perspectives to better characterize SARS-CoV-2 and its effects on humans. Our results indicate that the virus responsible for COVID–19 exhibits expected similarities, such as to Influenza A and Human Respiratory Syncytial viruses, and unexpected ones with different infection types and from distant viral families, like HIV1 and Human Herpes virus. Taken together, our findings indicate that COVID–19 is a systemic disease with potential effects on the function of multiple organs and human body sub-systems

CovMulNet19, Integrating Proteins, Diseases, Drugs, and Symptoms: A Network Medicine Approach to COVID-19

Introduction: We introduce in this study CovMulNet19, a comprehensive COVID-19 network containing all available known interactions involving SARS-CoV-2 proteins, interacting-human proteins, diseases and symptoms that are related to these human proteins, and compounds that can potentially target them. Materials and Methods: Extensive network analysis methods, based on a bootstrap approach, allow us to prioritize a list of diseases that display a high similarity to COVID-19 and a list of drugs that could potentially be beneficial to treat patients. As a key feature of CovMulNet19, the inclusion of symptoms allows a deeper characterization of the disease pathology, representing a useful proxy for COVID-19-related molecular processes. Results: We recapitulate many of the known symptoms of the disease and we find the most similar diseases to COVID-19 reflect conditions that are risk factors in patients. In particular, the comparison between CovMulNet19 and randomized networks recovers many of the known associated comorbidities that are important risk factors for COVID-19 patients, through identified similarities with intestinal, hepatic, and neurological diseases as well as with respiratory conditions, in line with reported comorbidities. Conclusion: CovMulNet19 can be suitably used for network medicine analysis, as a valuable tool for exploring drug repurposing while accounting for the intervening multidimensional factors, from molecular interactions to symptoms.Peer ReviewedPostprint (published version

Multilayer Network Science

Networks are convenient mathematical models to represent the structure of complex systems, from cells to societies. In the last decade, multilayer network science – the branch of the field dealing with units interacting in multiple distinct ways, simultaneously – was demonstrated to be an effective modeling and analytical framework for a wide spectrum of empirical systems, from biopolymers networks (such as interactome and metabolomes) to neuronal networks (such as connectomes), from social networks to urban and transportation networks. In this Element, a decade after one of the most seminal papers on this topic, the authors review the most salient features of multilayer network science, covering both theoretical aspects and direct applications to real-world coupled/interdependent systems, from the point of view of multilayer structure, dynamics and function. The authors discuss potential frontiers for this topic and the corresponding challenges in the field for the next future