Individualized epidemic spreading models predict epilepsy surgery outcomes: A pseudo-prospective study.

Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but up to 50% of patients continue to have seizures one year after the resection. In order to aid presurgical planning and predict postsurgical outcome on a patient-by-patient basis, we developed a framework of individualized computational models that combines epidemic spreading with patient-specific connectivity and epileptogeneity maps: the Epidemic Spreading Seizure and Epilepsy Surgery framework (ESSES). ESSES parameters were fitted in a retrospective study (N = 15) to reproduce invasive electroencephalography (iEEG)-recorded seizures. ESSES reproduced the iEEG-recorded seizures, and significantly better so for patients with good (seizure-free, SF) than bad (nonseizure-free, NSF) outcome. We illustrate here the clinical applicability of ESSES with a pseudo-prospective study (N = 34) with a blind setting (to the resection strategy and surgical outcome) that emulated presurgical conditions. By setting the model parameters in the retrospective study, ESSES could be applied also to patients without iEEG data. ESSES could predict the chances of good outcome after any resection by finding patient-specific model-based optimal resection strategies, which we found to be smaller for SF than NSF patients, suggesting an intrinsic difference in the network organization or presurgical evaluation results of NSF patients. The actual surgical plan overlapped more with the model-based optimal resection, and had a larger effect in decreasing modeled seizure propagation, for SF patients than for NSF patients. Overall, ESSES could correctly predict 75% of NSF and 80.8% of SF cases pseudo-prospectively. Our results show that individualised computational models may inform surgical planning by suggesting alternative resections and providing information on the likelihood of a good outcome after a proposed resection. This is the first time that such a model is validated with a fully independent cohort and without the need for iEEG recordings.

Individualized computational models of epilepsy surgery capture some of the key aspects of seizure propagation and the resective surgery. It is to be established whether this information can be integrated during the presurgical evaluation of the patient to improve surgical planning and the chances of a good surgical outcome. Here we address this question with a pseudo-prospective study that applies a computational framework of seizure propagation and epilepsy surgery­the ESSES framework­in a pseudo-prospective study mimicking the presurgical conditions. We found that within this pseudo-prospective setting, ESSES could correctly predict 75% of NSF and 80.8% of SF cases. This finding suggests the potential of individualised computational models to inform surgical planning by suggesting alternative resections and providing information on the likelihood of a good outcome after a proposed resection.

Reporting delays: A widely neglected impact factor in COVID-19 forecasts.

Epidemic forecasts are only as good as the accuracy of epidemic measurements. Is epidemic data, particularly COVID-19 epidemic data, clean, and devoid of noise? The complexity and variability inherent in data collection and reporting suggest otherwise. While we cannot evaluate the integrity of the COVID-19 epidemic data in a holistic fashion, we can assess the data for the presence of reporting delays. In our work, through the analysis of the first COVID-19 wave, we find substantial reporting delays in the published epidemic data. Motivated by the desire to enhance epidemic forecasts, we develop a statistical framework to detect, uncover, and remove reporting delays in the infectious, recovered, and deceased epidemic time series. Using our framework, we expose and analyze reporting delays in eight regions significantly affected by the first COVID-19 wave. Further, we demonstrate that removing reporting delays from epidemic data by using our statistical framework may decrease the error in epidemic forecasts. While our statistical framework can be used in combination with any epidemic forecast method that intakes infectious, recovered, and deceased data, to make a basic assessment, we employed the classical SIRD epidemic model. Our results indicate that the removal of reporting delays from the epidemic data may decrease the forecast error by up to 50%. We anticipate that our framework will be indispensable in the analysis of novel COVID-19 strains and other existing or novel infectious diseases.

Transition from time-variant to static networks: Timescale separation in N-intertwined mean-field approximation of susceptible-infectious-susceptible epidemics.

We extend the N-intertwined mean-field approximation (NIMFA) for the susceptible-infectious-susceptible (SIS) epidemiological process to time-varying networks. Processes on time-varying networks are often analyzed under the assumption that the process and network evolution happen on different timescales. This approximation is called timescale separation. We investigate timescale separation between disease spreading and topology updates of the network. We introduce the transition times [under T]̲(r) and T[over ¯](r) as the boundaries between the intermediate regime and the annealed (fast changing network) and quenched (static network) regimes, respectively, for a fixed accuracy tolerance r. By analyzing the convergence of static NIMFA processes, we analytically derive upper and lower bounds for T[over ¯](r). Our results provide insights and bounds on the time of convergence to the steady state of the static NIMFA SIS process. We show that, under our assumptions, the upper-transition time T[over ¯](r) is almost entirely determined by the basic reproduction number R_{0} of the network. The value of the upper-transition time T[over ¯](r) around the epidemic threshold is large, which agrees with the current understanding that some real-world epidemics cannot be approximated with the aforementioned timescale separation.

Recovering Power Grids Using Strategies Based on Network Metrics and Greedy Algorithms.

For this study, we investigated efficient strategies for the recovery of individual links in power grids governed by the direct current (DC) power flow model, under random link failures. Our primary objective was to explore the efficacy of recovering failed links based solely on topological network metrics. In total, we considered 13 recovery strategies, which encompassed 2 strategies based on link centrality values (link betweenness and link flow betweenness), 8 strategies based on the products of node centrality values at link endpoints (degree, eigenvector, weighted eigenvector, closeness, electrical closeness, weighted electrical closeness, zeta vector, and weighted zeta vector), and 2 heuristic strategies (greedy recovery and two-step greedy recovery), in addition to the random recovery strategy. To evaluate the performance of these proposed strategies, we conducted simulations on three distinct power systems: the IEEE 30, IEEE 39, and IEEE 118 systems. Our findings revealed several key insights: Firstly, there were notable variations in the performance of the recovery strategies based on topological network metrics across different power systems. Secondly, all such strategies exhibited inferior performance when compared to the heuristic recovery strategies. Thirdly, the two-step greedy recovery strategy consistently outperformed the others, with the greedy recovery strategy ranking second. Based on our results, we conclude that relying solely on a single metric for the development of a recovery strategy is insufficient when restoring power grids following link failures. By comparison, recovery strategies employing greedy algorithms prove to be more effective choices.

The role of epidemic spreading in seizure dynamics and epilepsy surgery.

Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but only leads to seizure freedom for roughly two in three patients. To address this problem, we designed a patient-specific epilepsy surgery model combining large-scale magnetoencephalography (MEG) brain networks with an epidemic spreading model. This simple model was enough to reproduce the stereo-tactical electroencephalography (SEEG) seizure propagation patterns of all patients (N = 15), when considering the resection areas (RA) as the epidemic seed. Moreover, the goodness of fit of the model predicted surgical outcome. Once adapted for each patient, the model can generate alternative hypothesis of the seizure onset zone and test different resection strategies in silico. Overall, our findings indicate that spreading models based on patient-specific MEG connectivity can be used to predict surgical outcomes, with better fit results and greater reduction on seizure propagation linked to higher likelihood of seizure freedom after surgery. Finally, we introduced a population model that can be individualized by considering only the patient-specific MEG network, and showed that it not only conserves but improves the group classification. Thus, it may pave the way to generalize this framework to patients without SEEG recordings, reduce the risk of overfitting and improve the stability of the analyses.

Topological properties and organizing principles of semantic networks.

Interpreting natural language is an increasingly important task in computer algorithms due to the growing availability of unstructured textual data. Natural Language Processing (NLP) applications rely on semantic networks for structured knowledge representation. The fundamental properties of semantic networks must be taken into account when designing NLP algorithms, yet they remain to be structurally investigated. We study the properties of semantic networks from ConceptNet, defined by 7 semantic relations from 11 different languages. We find that semantic networks have universal basic properties: they are sparse, highly clustered, and many exhibit power-law degree distributions. Our findings show that the majority of the considered networks are scale-free. Some networks exhibit language-specific properties determined by grammatical rules, for example networks from highly inflected languages, such as e.g. Latin, German, French and Spanish, show peaks in the degree distribution that deviate from a power law. We find that depending on the semantic relation type and the language, the link formation in semantic networks is guided by different principles. In some networks the connections are similarity-based, while in others the connections are more complementarity-based. Finally, we demonstrate how knowledge of similarity and complementarity in semantic networks can improve NLP algorithms in missing link inference.

Predicting network dynamics without requiring the knowledge of the interaction graph.

A network consists of two interdependent parts: the network topology or graph, consisting of the links between nodes and the network dynamics, specified by some governing equations. A crucial challenge is the prediction of dynamics on networks, such as forecasting the spread of an infectious disease on a human contact network. Unfortunately, an accurate prediction of the dynamics seems hardly feasible, because the network is often complicated and unknown. In this work, given past observations of the dynamics on a fixed graph, we show the contrary: Even without knowing the network topology, we can predict the dynamics. Specifically, for a general class of deterministic governing equations, we propose a two-step prediction algorithm. First, we obtain a surrogate network by fitting past observations of every nodal state to the dynamical model. Second, we iterate the governing equations on the surrogate network to predict the dynamics. Surprisingly, even though there is no similarity between the surrogate topology and the true topology, the predictions are accurate, for a considerable prediction time horizon, for a broad range of observation times, and in the presence of a reasonable noise level. The true topology is not needed for predicting dynamics on networks, since the dynamics evolve in a subspace of astonishingly low dimension compared to the size and heterogeneity of the graph. Our results constitute a fresh perspective on the broad field of nonlinear dynamics on complex networks.

Fréchet distribution in geometric graphs for drone networks.

In this paper, we focus on the link density in random geometric graphs (RGGs) with a distance-based connection function. After deriving the link density in D dimensions, we focus on the two-dimensional (2D) and three-dimensional (3D) space and show that the link density is accurately approximated by the Fréchet distribution, for any rectangular space. We derive expressions, in terms of the link density, for the minimum number of nodes needed in the 2D and 3D spaces to ensure network connectivity. These results provide first-order estimates for, e.g., a swarm of drones to provide coverage in a disaster or crowded area.

Moment closure approximations of susceptible-infected-susceptible epidemics on adaptive networks.

The influence of people's individual responses to the spread of contagious phenomena, like the COVID-19 pandemic, is still not well understood. We investigate the Markovian Generalized Adaptive Susceptible-Infected-Susceptible (G-ASIS) epidemic model. The G-ASIS model comprises many contagious phenomena on networks, ranging from epidemics and information diffusion to innovation spread and human brain interactions. The connections between nodes in the G-ASIS model change adaptively over time, because nodes make decisions to create or break links based on the health state of their neighbors. Our contribution is fourfold. First, we rigorously derive the first-order and second-order mean-field approximations from the continuous-time Markov chain. Second, we illustrate that the first-order mean-field approximation fails to approximate the epidemic threshold of the Markovian G-ASIS model accurately. Third, we show that the second-order mean-field approximation is a qualitative good approximation of the Markovian G-ASIS model. Finally, we discuss the Adaptive Information Diffusion (AID) model in detail, which is contained in the G-ASIS model. We show that, similar to most other instances of the G-ASIS model, the AID model possesses a unique steady state, but that in the AID model, the convergence time toward the steady state is very large. Our theoretical results are supported by numerical simulations.

Predicting time-resolved electrophysiological brain networks from structural eigenmodes.

How temporal modulations in functional interactions are shaped by the underlying anatomical connections remains an open question. Here, we analyse the role of structural eigenmodes, in the formation and dissolution of temporally evolving functional brain networks using resting-state magnetoencephalography and diffusion magnetic resonance imaging data at the individual subject level. Our results show that even at short timescales, phase and amplitude connectivity can partly be expressed by structural eigenmodes, but hardly by direct structural connections. Albeit a stronger relationship was found between structural eigenmodes and time-resolved amplitude connectivity. Time-resolved connectivity for both phase and amplitude was mostly characterised by a stationary process, superimposed with very brief periods that showed deviations from this stationary process. For these brief periods, dynamic network states were extracted that showed different expressions of eigenmodes. Furthermore, the eigenmode expression was related to overall cognitive performance and co-occurred with fluctuations in community structure of functional networks. These results implicate that ongoing time-resolved resting-state networks, even at short timescales, can to some extent be understood in terms of activation and deactivation of structural eigenmodes and that these eigenmodes play a role in the dynamic integration and segregation of information across the cortex, subserving cognitive functions.

Analysis of continuous-time Markovian ɛ-SIS epidemics on networks.

We analyze continuous-time Markovian ɛ-SIS epidemics with self-infections on the complete graph. The majority of the graphs are analytically intractable, but many physical features of the ɛ-SIS process observed in the complete graph can occur in any other graph. In this work, we illustrate that the timescales of the ɛ-SIS process are related to the eigenvalues of the tridiagonal matrix of the SIS Markov chain. We provide a detailed analysis of all eigenvalues and illustrate that the eigenvalues show staircases, which are caused by the nearly degenerate (but strictly distinct) pairs of eigenvalues. We also illustrate that the ratio between the second-largest and third-largest eigenvalue is a good indicator of metastability in the ɛ-SIS process. Additionally, we show that the epidemic threshold of the Markovian ɛ-SIS process can be accurately approximated by the effective infection rate for which the third-largest eigenvalue of the transition matrix is the smallest. Finally, we derive the exact mean-field solution for the ɛ-SIS process on the complete graph, and we show that the mean-field approximation does not correctly represent the metastable behavior of Markovian ɛ-SIS epidemics.

Epidemic models characterize seizure propagation and the effects of epilepsy surgery in individualized brain networks based on MEG and invasive EEG recordings.

Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients. However, seizure-freedom is currently achieved in only 2/3 of the patients after surgery. In this study we have developed an individualized computational model based on MEG brain networks to explore seizure propagation and the efficacy of different virtual resections. Eventually, the goal is to obtain individualized models to optimize resection strategy and outcome. We have modelled seizure propagation as an epidemic process using the susceptible-infected (SI) model on individual brain networks derived from presurgical MEG. We included 10 patients who had received epilepsy surgery and for whom the surgery outcome at least one year after surgery was known. The model parameters were tuned in in order to reproduce the patient-specific seizure propagation patterns as recorded with invasive EEG. We defined a personalized search algorithm that combined structural and dynamical information to find resections that maximally decreased seizure propagation for a given resection size. The optimal resection for each patient was defined as the smallest resection leading to at least a 90% reduction in seizure propagation. The individualized model reproduced the basic aspects of seizure propagation for 9 out of 10 patients when using the resection area as the origin of epidemic spreading, and for 10 out of 10 patients with an alternative definition of the seed region. We found that, for 7 patients, the optimal resection was smaller than the resection area, and for 4 patients we also found that a resection smaller than the resection area could lead to a 100% decrease in propagation. Moreover, for two cases these alternative resections included nodes outside the resection area. Epidemic spreading models fitted with patient specific data can capture the fundamental aspects of clinically observed seizure propagation, and can be used to test virtual resections in silico. Combined with optimization algorithms, smaller or alternative resection strategies, that are individually targeted for each patient, can be determined with the ultimate goal to improve surgery outcome. MEG-based networks can provide a good approximation of structural connectivity for computational models of seizure propagation, and facilitate their clinical use.

Accuracy of predicting epidemic outbreaks.

During the outbreak of a virus, perhaps the greatest concern is the future evolution of the epidemic: How many people will be infected and which regions will be affected the most? The accurate prediction of an epidemic enables targeted disease countermeasures (e.g., allocating medical staff and quarantining). But when can we trust the prediction of an epidemic to be accurate? In this work we consider susceptible-infected-susceptible (SIS) and susceptible-infected-removed (SIR) epidemics on networks with time-invariant spreading parameters. (For time-varying spreading parameters, our results correspond to an optimistic scenario for the predictability of epidemics.) Our contribution is twofold. First, accurate long-term predictions of epidemics are possible only after the peak rate of new infections. Hence, before the peak, only short-term predictions are reliable. Second, we define an exponential growth metric, which quantifies the predictability of an epidemic. In particular, even without knowing the future evolution of the epidemic, the growth metric allows us to compare the predictability of an epidemic at different points in time. Our results are an important step towards understanding when and why epidemics can be predicted reliably.

Comparing the accuracy of several network-based COVID-19 prediction algorithms.

Researchers from various scientific disciplines have attempted to forecast the spread of coronavirus disease 2019 (COVID-19). The proposed epidemic prediction methods range from basic curve fitting methods and traffic interaction models to machine-learning approaches. If we combine all these approaches, we obtain the Network Inference-based Prediction Algorithm (NIPA). In this paper, we analyse a diverse set of COVID-19 forecast algorithms, including several modifications of NIPA. Among the algorithms that we evaluated, the original NIPA performed best at forecasting the spread of COVID-19 in Hubei, China and in the Netherlands. In particular, we show that network-based forecasting is superior to any other forecasting algorithm.

Optimization of epilepsy surgery through virtual resections on individual structural brain networks.

The success of epilepsy surgery in patients with refractory epilepsy depends upon correct identification of the epileptogenic zone (EZ) and an optimal choice of the resection area. In this study we developed individualized computational models based upon structural brain networks to explore the impact of different virtual resections on the propagation of seizures. The propagation of seizures was modelled as an epidemic process [susceptible-infected-recovered (SIR) model] on individual structural networks derived from presurgical diffusion tensor imaging in 19 patients. The candidate connections for the virtual resection were all connections from the clinically hypothesized EZ, from which the seizures were modelled to start, to other brain areas. As a computationally feasible surrogate for the SIR model, we also removed the connections that maximally reduced the eigenvector centrality (EC) (large values indicate network hubs) of the hypothesized EZ, with a large reduction meaning a large effect. The optimal combination of connections to be removed for a maximal effect were found using simulated annealing. For comparison, the same number of connections were removed randomly, or based on measures that quantify the importance of a node or connection within the network. We found that 90% of the effect (defined as reduction of EC of the hypothesized EZ) could already be obtained by removing substantially less than 90% of the connections. Thus, a smaller, optimized, virtual resection achieved almost the same effect as the actual surgery yet at a considerably smaller cost, sparing on average 27.49% (standard deviation: 4.65%) of the connections. Furthermore, the maximally effective connections linked the hypothesized EZ to hubs. Finally, the optimized resection was equally or more effective than removal based on structural network characteristics both regarding reducing the EC of the hypothesized EZ and seizure spreading. The approach of using reduced EC as a surrogate for simulating seizure propagation can suggest more restrictive resection strategies, whilst obtaining an almost optimal effect on reducing seizure propagation, by taking into account the unique topology of individual structural brain networks of patients.

Clustering for epidemics on networks: A geometric approach.

Infectious diseases typically spread over a contact network with millions of individuals, whose sheer size is a tremendous challenge to analyzing and controlling an epidemic outbreak. For some contact networks, it is possible to group individuals into clusters. A high-level description of the epidemic between a few clusters is considerably simpler than on an individual level. However, to cluster individuals, most studies rely on equitable partitions, a rather restrictive structural property of the contact network. In this work, we focus on Susceptible-Infected-Susceptible (SIS) epidemics, and our contribution is threefold. First, we propose a geometric approach to specify all networks for which an epidemic outbreak simplifies to the interaction of only a few clusters. Second, for the complete graph and any initial viral state vectors, we derive the closed-form solution of the nonlinear differential equations of the N-intertwined mean-field approximation of the SIS process. Third, by relaxing the notion of equitable partitions, we derive low-complexity approximations and bounds for epidemics on arbitrary contact networks. Our results are an important step toward understanding and controlling epidemics on large networks.

Network-based prediction of COVID-19 epidemic spreading in Italy.

Initially emerged in the Chinese city Wuhan and subsequently spread almost worldwide causing a pandemic, the SARS-CoV-2 virus follows reasonably well the Susceptible-Infectious-Recovered (SIR) epidemic model on contact networks in the Chinese case. In this paper, we investigate the prediction accuracy of the SIR model on networks also for Italy. Specifically, the Italian regions are a metapopulation represented by network nodes and the network links are the interactions between those regions. Then, we modify the network-based SIR model in order to take into account the different lockdown measures adopted by the Italian Government in the various phases of the spreading of the COVID-19. Our results indicate that the network-based model better predicts the daily cumulative infected individuals when time-varying lockdown protocols are incorporated in the classical SIR model.

Time-dependent solution of the NIMFA equations around the epidemic threshold.

The majority of epidemic models are described by non-linear differential equations which do not have a closed-form solution. Due to the absence of a closed-form solution, the understanding of the precise dynamics of a virus is rather limited. We solve the differential equations of the N-intertwined mean-field approximation of the susceptible-infected-susceptible epidemic process with heterogeneous spreading parameters around the epidemic threshold for an arbitrary contact network, provided that the initial viral state vector is small or parallel to the steady-state vector. Numerical simulations demonstrate that the solution around the epidemic threshold is accurate, also above the epidemic threshold and for general initial viral states that are below the steady-state.

Network-inference-based prediction of the COVID-19 epidemic outbreak in the Chinese province Hubei.

At the moment of writing, the future evolution of the COVID-19 epidemic is unclear. Predictions of the further course of the epidemic are decisive to deploy targeted disease control measures. We consider a network-based model to describe the COVID-19 epidemic in the Hubei province. The network is composed of the cities in Hubei and their interactions (e.g., traffic flow). However, the precise interactions between cities is unknown and must be inferred from observing the epidemic. We propose the Network-Inference-Based Prediction Algorithm (NIPA) to forecast the future prevalence of the COVID-19 epidemic in every city. Our results indicate that NIPA is beneficial for an accurate forecast of the epidemic outbreak.

Classification of link-breaking and link-creation updating rules in susceptible-infected-susceptible epidemics on adaptive networks.

In the classical susceptible-infected-susceptible (SIS) model, a disease or infection spreads over a given, mostly fixed graph. However, in many real complex networks, the topology of the underlying graph can change due to the influence of the dynamical process. In this paper, besides the spreading process, the network adaptively changes its topology based on the states of the nodes in the network. An entire class of link-breaking and link-creation mechanisms, which we name Generalized Adaptive SIS (G-ASIS), is presented and analyzed. For each instance of G-ASIS using the complete graph as initial network, the relation between the epidemic threshold and the effective link-breaking rate is determined to be linear, constant, or unknown. Additionally, we show that there exist link-breaking and link-creation mechanisms for which the metastable state does not exist. We confirm our theoretical results with several numerical simulations.