Network bypasses sustain complexity.

Real-world networks are neither regular nor random, a fact elegantly explained by mechanisms such as the Watts-Strogatz or the Barabási-Albert models, among others. Both mechanisms naturally create shortcuts and hubs, which while enhancing the network's connectivity, also might yield several undesired navigational effects: They tend to be overused during geodesic navigational processes-making the networks fragile-and provide suboptimal routes for diffusive-like navigation. Why, then, networks with complex topologies are ubiquitous? Here, we unveil that these models also entropically generate network bypasses: alternative routes to shortest paths which are topologically longer but easier to navigate. We develop a mathematical theory that elucidates the emergence and consolidation of network bypasses and measure their navigability gain. We apply our theory to a wide range of real-world networks and find that they sustain complexity by different amounts of network bypasses. At the top of this complexity ranking we found the human brain, which points out the importance of these results to understand the plasticity of complex systems.

Topologically induced suppression of explosive synchronization.

Nowadays, explosive synchronization is a well-documented phenomenon consisting in a first-order transition that may coexist with classical synchronization. Typically, explosive synchronization occurs when the network structure is represented by the classical graph Laplacian, and the node frequency and its degree are correlated. Here, we answer the question on whether this phenomenon can be observed in networks when the oscillators are coupled via degree-biased Laplacian operators. We not only observe that this is the case but also that this new representation naturally controls the transition from explosive to standard synchronization in a network. We prove analytically that explosive synchronization emerges when using this theoretical setting in star-like networks. As soon as this star-like network is topologically converted into a network containing cycles, the explosive synchronization gives rise to classical synchronization. Finally, we hypothesize that this mechanism may play a role in switching from normal to explosive states in the brain, where explosive synchronization has been proposed to be related to some pathologies like epilepsy and fibromyalgia.

What Is in a Simplicial Complex? A Metaplex-Based Approach to Its Structure and Dynamics.

Geometric realization of simplicial complexes makes them a unique representation of complex systems. The existence of local continuous spaces at the simplices level with global discrete connectivity between simplices makes the analysis of dynamical systems on simplicial complexes a challenging problem. In this work, we provide some examples of complex systems in which this representation would be a more appropriate model of real-world phenomena. Here, we generalize the concept of metaplexes to embrace that of geometric simplicial complexes, which also includes the definition of dynamical systems on them. A metaplex is formed by regions of a continuous space of any dimension interconnected by sinks and sources that works controlled by discrete (graph) operators. The definition of simplicial metaplexes given here allows the description of the diffusion dynamics of this system in a way that solves the existing problems with previous models. We make a detailed analysis of the generalities and possible extensions of this model beyond simplicial complexes, e.g., from polytopal and cell complexes to manifold complexes, and apply it to a real-world simplicial complex representing the visual cortex of a macaque.

COVID-19 and SARS-CoV-2. Modeling the present, looking at the future.

Since December 2019 the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an outbreak of pulmonary disease which has soon become a global pandemic, known as COronaVIrus Disease-19 (COVID-19). The new coronavirus shares about 82% of its genome with the one which produced the 2003 outbreak (SARS CoV-1). Both coronaviruses also share the same cellular receptor, which is the angiotensin-converting enzyme 2 (ACE2) one. In spite of these similarities, the new coronavirus has expanded more widely, more faster and more lethally than the previous one. Many researchers across the disciplines have used diverse modeling tools to analyze the impact of this pandemic at global and local scales. This includes a wide range of approaches - deterministic, data-driven, stochastic, agent-based, and their combinations - to forecast the progression of the epidemic as well as the effects of non-pharmaceutical interventions to stop or mitigate its impact on the world population. The physical complexities of modern society need to be captured by these models. This includes the many ways of social contacts - (multiplex) social contact networks, (multilayers) transport systems, metapopulations, etc. - that may act as a framework for the virus propagation. But modeling not only plays a fundamental role in analyzing and forecasting epidemiological variables, but it also plays an important role in helping to find cures for the disease and in preventing contagion by means of new vaccines. The necessity for answering swiftly and effectively the questions: could existing drugs work against SARS CoV-2? and can new vaccines be developed in time? demands the use of physical modeling of proteins, protein-inhibitors interactions, virtual screening of drugs against virus targets, predicting immunogenicity of small peptides, modeling vaccinomics and vaccine design, to mention just a few. Here, we review these three main areas of modeling research against SARS CoV-2 and COVID-19: (1) epidemiology; (2) drug repurposing; and (3) vaccine design. Therefore, we compile the most relevant existing literature about modeling strategies against the virus to help modelers to navigate this fast-growing literature. We also keep an eye on future outbreaks, where the modelers can find the most relevant strategies used in an emergency situation as the current one to help in fighting future pandemics.

Quantum Interference, Graphs, Walks, and Polynomials.

In this paper, we explore quantum interference (QI) in molecular conductance from the point of view of graph theory and walks on lattices. By virtue of the Cayley-Hamilton theorem for characteristic polynomials and the Coulson-Rushbrooke pairing theorem for alternant hydrocarbons, it is possible to derive a finite series expansion of the Green's function for electron transmission in terms of the odd powers of the vertex adjacency matrix or Hückel matrix. This means that only odd-length walks on a molecular graph contribute to the conductivity through a molecule. Thus, if there are only even-length walks between two atoms, quantum interference is expected to occur in the electron transport between them. However, even if there are only odd-length walks between two atoms, a situation may come about where the contributions to the QI of some odd-length walks are canceled by others, leading to another class of quantum interference. For nonalternant hydrocarbons, the finite Green's function expansion may include both even and odd powers. Nevertheless, QI can in some circumstances come about for nonalternants from cancellation of odd- and even-length walk terms. We report some progress, but not a complete resolution, of the problem of understanding the coefficients in the expansion of the Green's function in a power series of the adjacency matrix, these coefficients being behind the cancellations that we have mentioned. Furthermore, we introduce a perturbation theory for transmission as well as some potentially useful infinite power series expansions of the Green's function.

Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2.

The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.

Topological analysis of SARS CoV-2 main protease.

There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro.

Influence of long-range interactions on quantum interference in molecular conduction. A tight-binding (Hückel) approach.

When certain pairs of atoms in a π-conjugated molecule are connected with nanometer-scale source and drain electrodes, the remarkable quantum interference (QI) effect may arise. In this case, the electron transmission probability is significantly suppressed due to the QI effect. Tight-binding approaches, such as the Hückel molecular orbital (HMO) model, have revealed important features of this quantum phenomenon. However, important deviations from experiments and from more sophisticated calculations are known for a variety of cases. Here, we propose an extension of the HMO method to include non-nearest-neighbor interactions. Such long-range interactions (LRIs) are implemented in the HMO model in the form of a damping function that decays as the topological distance-the number of bonds separating two atoms-gets larger. The proposed model is further developed so that a geometric modification, i.e., the rotation around a single bond, can be taken into account. Our results show that LRI affects both the location of the antiresonance peak due to QI and the intensity of QI, even suppressing it in some cases. These results agree well with what was observed in a Density Functional based Tight-Binding (DFTB) study reported in the literature. These properties can be interpreted on the basis of a graph-theoretic path-counting model as well as the molecular orbital theory. In addition, the geometric LRI model is shown to reproduce the change of transmission as a function of rotation around the single bond separating two benzene rings in biphenyl, in agreement with what was observed in both experiment and DFTB calculation.

Economic impact of refugees.

In 2015, the United Nations High Commission for Refugees accommodated over 15 million refugees, mostly in refugee camps in developing countries. The World Food Program provided these refugees with food aid, in cash or in kind. Refugees' impacts on host countries are controversial and little understood. This unique study analyzes the economic impacts of refugees on host-country economies within a 10-km radius of three Congolese refugee camps in Rwanda. Simulations using Monte Carlo methods reveal that cash aid to refugees creates significant positive income spillovers to host-country businesses and households. An additional adult refugee receiving cash aid increases annual real income in the local economy by $205 to $253, significantly more than the $120-$126 in aid each refugee receives. Trade between the local economy and the rest of Rwanda increases by $49 to $55. The impacts are lower for in-kind food aid, a finding relevant to development aid generally.

Centralities in simplicial complexes. Applications to protein interaction networks.

Complex networks can be used to represent complex systems which originate in the real world. Here we study a transformation of these complex networks into simplicial complexes, where cliques represent the simplices of the complex. We extend the concept of node centrality to that of simplicial centrality and study several mathematical properties of degree, closeness, betweenness, eigenvector, Katz, and subgraph centrality for simplicial complexes. We study the degree distributions of these centralities at the different levels. We also compare and describe the differences between the centralities at the different levels. Using these centralities we study a method for detecting essential proteins in PPI networks of cells and explain the varying abilities of the centrality measures at the different levels in identifying these essential proteins.

Epidemics on plants: Modeling long-range dispersal on spatially embedded networks.

Here we develop an epidemic model that accounts for long-range dispersal of pathogens between plants. This model generalizes the classical compartmental models-Susceptible-Infected-Susceptible (SIS) and Susceptible-Infected-Recovered (SIR)-to take into account those factors that are key to understand epidemics in real plant populations. These ingredients are the spatial characteristics of the plots and fields in which plants are embedded and the effect of long-range dispersal of pathogens. The spatial characteristics are included through the use of random rectangular graphs which allow to consider the effects of the elongation of plots and fields, while the long-range dispersal is implemented by considering transformations, such as the Mellin and Laplace transforms, of a generalization of the adjacency matrix of the geometric graph. Our results point out that long-range dispersal favors the propagation of pathogens while the elongation of plant plots increases the epidemic threshold and decreases dramatically the number of affected plants. Interestingly, our model is able of reproducing the existence of patchy regions of infected plants and the absence of a clear propagation front centered in the initial infected plants, as it is observed in real plant epidemics.

Exploring the "Middle Earth" of network spectra via a Gaussian matrix function.

We study a Gaussian matrix function of the adjacency matrix of artificial and real-world networks. We motivate the use of this function on the basis of a dynamical process modeled by the time-dependent Schrödinger equation with a squared Hamiltonian. In particular, we study the Gaussian Estrada index-an index characterizing the importance of eigenvalues close to zero. This index accounts for the information contained in the eigenvalues close to zero in the spectra of networks. Such a method is a generalization of the so-called "Folded Spectrum Method" used in quantum molecular sciences. Here, we obtain bounds for this index in simple graphs, proving that it reaches its maximum for star graphs followed by complete bipartite graphs. We also obtain formulas for the Estrada Gaussian index of Erdos-Rényi random graphs and for the Barabási-Albert graphs. We also show that in real-world networks, this index is related to the existence of important structural patterns, such as complete bipartite subgraphs (bicliques). Such bicliques appear naturally in many real-world networks as a consequence of the evolutionary processes giving rise to them. In general, the Gaussian matrix function of the adjacency matrix of networks characterizes important structural information not described in previously used matrix functions of graphs.

Synchronizability of random rectangular graphs.

Random rectangular graphs (RRGs) represent a generalization of the random geometric graphs in which the nodes are embedded into hyperrectangles instead of on hypercubes. The synchronizability of RRG model is studied. Both upper and lower bounds of the eigenratio of the network Laplacian matrix are determined analytically. It is proven that as the rectangular network is more elongated, the network becomes harder to synchronize. The synchronization processing behavior of a RRG network of chaotic Lorenz system nodes is numerically investigated, showing complete consistence with the theoretical results.

Food intake and nutrition in children 1-4 years of age in Yucatan, Mexico.

BACKGROUND: The National Health and Nutrition Survey 2006 (ENSANUT in Spanish) reported high rates of under-nutrition in children of Yucatan. Is food intake the main cause of under-nutrition in children of the state of Yucatan, Mexico? AIM: Identify the primary causes of under-nutrition in pre-school children in Yucatan. SUBJECTS: A sample of 111 children (59 girls and 52 boys) aged 1-4 years representing Yucatan was taken from a database of ENSANUT 2006 and another national survey, a federal poverty mitigation programme for the state of Yucatan, Mexico entitled "Oportunidades". METHODS: A human ecology approach together with life history theory was used to analyse anthropometric indices and food intake data from the ENSANUT 2006 and "Oportunidades". RESULTS: Height and weight were significantly correlated to age and total food intake. No correlations were found between age and anthropometric indices or food intake rates. The children in the sample had adequate protein intake but deficient energy intake. No correlation was identified between nutritional status and food intake rates. Pre-schoolers with higher weight-for-height values achieved greater height-for-age. These relationships can be explained by life history theory in that energy intake was used either for maintenance (combating and recovering from infections) or growth. CONCLUSION: The poor relationship between food intake rates and nutritional status is probably explained by the interaction between high disease incidence and insufficient energy intake. These conditions are endemic in Yucatan due to widespread poor housing, water and sanitation conditions.

The world-wide waste web.

Countries globally trade with tons of waste materials every year, some of which are highly hazardous. This trade admits a network representation of the world-wide waste web, with countries as vertices and flows as directed weighted edges. Here we investigate the main properties of this network by tracking 108 categories of wastes interchanged in the period 2001-2019. Although, most of the hazardous waste was traded between developed nations, a disproportionate asymmetry existed in the flow from developed to developing countries. Using a dynamical model, we simulate how waste stress propagates through the network and affects the countries. We identify 28 countries with low Environmental Performance Index that are at high risk of waste congestion. Therefore, they are at threat of improper handling and disposal of hazardous waste. We find evidence of pollution by heavy metals, by volatile organic compounds and/or by persistent organic pollutants, which are used as chemical fingerprints, due to the improper handling of waste in several of these countries.

Nonuniform random graphs on the plane: A scaling study.

We consider random geometric graphs on the plane characterized by a nonuniform density of vertices. In particular, we introduce a graph model where n vertices are independently distributed in the unit disk with positions, in polar coordinates (l,θ), obeying the probability density functions ρ(l) and ρ(θ). Here we choose ρ(l) as a normal distribution with zero mean and variance σ∈(0,∞) and ρ(θ) as a uniform distribution in the interval θ∈[0,2π). Then, two vertices are connected by an edge if their Euclidean distance is less than or equal to the connection radius ℓ. We characterize the topological properties of this random graph model, which depends on the parameter set (n,σ,ℓ), by the use of the average degree 〈k〉 and the number of nonisolated vertices V_{×}, while we approach their spectral properties with two measures on the graph adjacency matrix: the ratio of consecutive eigenvalue spacings r and the Shannon entropy S of eigenvectors. First we propose a heuristic expression for 〈k(n,σ,ℓ)〉. Then, we look for the scaling properties of the normalized average measure 〈X[over ¯]〉 (where X stands for V_{×}, r, and S) over graph ensembles. We demonstrate that the scaling parameter of 〈V_{×}[over ¯]〉=〈V_{×}〉/n is indeed 〈k〉, with 〈V_{×}[over ¯]〉≈1-exp(-〈k〉). Meanwhile, the scaling parameter of both 〈r[over ¯]〉 and 〈S[over ¯]〉 is proportional to n^{-γ}〈k〉 with γ≈0.16.

Community detection based on network communicability.

We propose a new method for detecting communities based on the concept of communicability between nodes in a complex network. This method, designated as N-ComBa K-means, uses a normalized version of the adjacency matrix to build the communicability matrix and then applies K-means clustering to find the communities in a graph. We analyze how this method performs for some pathological cases found in the analysis of the detection limit of communities and propose some possible solutions on the basis of the analysis of the ratio of local to global densities in graphs. We use four different quality criteria for detecting the best clustering and compare the new approach with the Girvan-Newman algorithm for the analysis of two "classical" networks: karate club and bottlenose dolphins. Finally, we analyze the more challenging case of homogeneous networks with community structure, for which the Girvan-Newman completely fails in detecting any clustering. The N-ComBa K-means approach performs very well in these situations and we applied it to detect the community structure in an international trade network of miscellaneous manufactures of metal having these characteristics. Some final remarks about the general philosophy of community detection are also discussed.

Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions.

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson's disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

Loss of structural balance in stock markets.

We use rank correlations as distance functions to establish the interconnectivity between stock returns, building weighted signed networks for the stocks of seven European countries, the US and Japan. We establish the theoretical relationship between the level of balance in a network and stock predictability, studying its evolution from 2005 to the third quarter of 2020. We find a clear balance-unbalance transition for six of the nine countries, following the August 2011 Black Monday in the US, when the Economic Policy Uncertainty index for this country reached its highest monthly level before the COVID-19 crisis. This sudden loss of balance is mainly caused by a reorganization of the market networks triggered by a group of low capitalization stocks belonging to the non-financial sector. After the transition, the stocks of companies in these groups become all negatively correlated between them and with most of the rest of the stocks in the market. The implied change in the network topology is directly related to a decrease in stock predictability, a finding with novel important implications for asset allocation and portfolio hedging strategies.

Universality in protein residue networks.

Residue networks representing 595 nonhomologous proteins are studied. These networks exhibit universal topological characteristics as they belong to the topological class of modular networks formed by several highly interconnected clusters separated by topological cavities. There are some networks that tend to deviate from this universality. These networks represent small-size proteins having <200 residues. This article explains such differences in terms of the domain structure of these proteins. On the other hand, the topological cavities characterizing proteins residue networks match very well with protein binding sites. This study investigates the effect of the cutoff value used in building the residue network. For small cutoff values, <5 A, the cavities found are very large corresponding almost to the whole protein surface. On the contrary, for large cutoff value, >10.0 A, only very large cavities are detected and the networks look very homogeneous. These findings are useful for practical purposes as well as for identifying protein-like complex networks. Finally, this article shows that the main topological class of residue networks is not reproduced by random networks growing according to Erdös-Rényi model or the preferential attachment method of Barabási-Albert. However, the Watts-Strogatz model reproduces very well the topological class as well as other topological properties of residue network. A more biologically appealing modification of the Watts-Strogatz model to describe residue networks is proposed.