Immunization using a heterogeneous geo-spatial population model: A qualitative perspective on COVID-19 vaccination strategies.

Epidemic modeling has been a key tool for understanding the impact of global viral outbreaks for over two decades. Recent developments of the COVID-19 pandemic have accelerated research using compartmental models, like SI, SIR, SEIR, with their appropriate modifications. However, there is a large body of recent research consolidated on homogeneous population mixing models, which are known to offer reduced tractability, and render conclusions hard to quantify. As such, based on our recent work, introducing the heterogeneous geo-spatial mobility population model (GPM), we adapt a modified SIR-V (susceptible-infected-recovered-vaccinated) epidemic model which embodies the idea of patient relapse from R back to S, vaccination of R and S patients (reducing their infectiousness), thus altering the infectiousness of V patients (from λn to λr). Simulation results spanning over a period of t = 2000 days (6 years, the period « 2020-2025) compare the impact of an epidemic outbreak with variable vaccination strategies, starting after 1 year (as is the case of COVID-19). The infected proportion in the remaining 5-year period is analyzed using vaccination rates from rv = 0 (no vaccination) to rv = 1. While rv < 0.4 is less effective during the earlier stages, all strategies with rv > 0.4 show a similar downward convergence reducing the number of infected by more than half, compared to no vaccination. Given the complexity of epidemic processes, we conclude that higher vaccination rates yield similar results, but a minimal rv = 0.4 (40% of population over five years) should be targeted.

A novel geo-hierarchical population mobility model for spatial spreading of resurgent epidemics.

Computational models for large, resurgent epidemics are recognized as a crucial tool for predicting the spread of infectious diseases. It is widely agreed, that such models can be augmented with realistic multiscale population models and by incorporating human mobility patterns. Nevertheless, a large proportion of recent studies, aimed at better understanding global epidemics, like influenza, measles, H1N1, SARS, and COVID-19, underestimate the role of heterogeneous mixing in populations, characterized by strong social structures and geography. Motivated by the reduced tractability of studies employing homogeneous mixing, which make conclusions hard to deduce, we propose a new, very fine-grained model incorporating the spatial distribution of population into geographical settlements, with a hierarchical organization down to the level of households (inside which we assume homogeneous mixing). In addition, population is organized heterogeneously outside households, and we model the movement of individuals using travel distance and frequency parameters for inter- and intra-settlement movement. Discrete event simulation, employing an adapted SIR model with relapse, reproduces important qualitative characteristics of real epidemics, like high variation in size and temporal heterogeneity (e.g., waves), that are challenging to reproduce and to quantify with existing measures. Our results pinpoint an important aspect, that epidemic size is more sensitive to the increase in distance of travel, rather that the frequency of travel. Finally, we discuss implications for the control of epidemics by integrating human mobility restrictions, as well as progressive vaccination of individuals.

Analyzing Neck Circumference as an Indicator of CPAP Treatment Response in Obstructive Sleep Apnea with Network Medicine.

We explored the relationship between obstructive sleep apnea (OSA) patients' anthropometric measures and the CPAP treatment response. To that end, we processed three non-overlapping cohorts (D1, D2, D3) with 1046 patients from four sleep laboratories in Western Romania, including 145 subjects (D1) with one-night CPAP therapy. Using D1 data, we created a CPAP-response network of patients, and found neck circumference (NC) as the most significant qualitative indicator for apnea-hypopnea index (AHI) improvement. We also investigated a quantitative NC cutoff value for OSA screening on cohorts D2 (OSA-diagnosed) and D3 (control), using the area under the curve. As such, we confirmed the correlation between NC and AHI (ρ=0.35, p<0.001) and showed that 71% of diagnosed male subjects had bigger NC values than subjects with no OSA (area under the curve is 0.71, with 95% CI 0.63-0.79, p<0.001); the optimal NC cutoff is 41 cm, with a sensitivity of 0.8099, a specificity of 0.5185, positive predicted value (PPV) = 0.9588, negative predicted value (NPV) = 0.1647, and positive likelihood ratio (LR+) = 1.68. Our NC =41 cm threshold classified the D1 patients' CPAP responses-measured as the difference in AHI prior to and after the one-night use of CPAP-with a sensitivity of 0.913 and a specificity of 0.859.

Gender Phenotyping of Patients with Obstructive Sleep Apnea Syndrome Using a Network Science Approach.

We defined gender-specific phenotypes for men and women diagnosed with obstructive sleep apnea syndrome (OSAS) based on easy-to-measure anthropometric parameters, using a network science approach. We collected data from 2796 consecutive patients since 2005, from 4 sleep laboratories in Western Romania, recording sleep, breathing, and anthropometric measurements. For both genders, we created specific apnea patient networks defined by patient compatibility relationships in terms of age, body mass index (BMI), neck circumference (NC), blood pressure (BP), and Epworth sleepiness score (ESS). We classified the patients with clustering algorithms, then statistically analyzed the groups/clusters. Our study uncovered eight phenotypes for each gender. We found that all males with OSAS have a large NC, followed by daytime sleepiness and high BP or obesity. Furthermore, all unique female phenotypes have high BP, followed by obesity and sleepiness. We uncovered gender-related differences in terms of associated OSAS parameters. In males, we defined the pattern large NC-sleepiness-high BP as an OSAS predictor, while in women, we found the pattern of high BP-obesity-sleepiness. These insights are useful for increasing awareness, improving diagnosis, and treatment response.

Uncovering New Drug Properties in Target-Based Drug-Drug Similarity Networks.

Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the biological environment is a complex system, the traditional approach-based on knowledge about the chemical structures-can not fully explain the nature of interactions between drugs and biological targets. Consequently, in this paper, we propose an unsupervised machine learning approach that uses the information we know about drug-target interactions to infer drug properties. To this end, we define drug similarity based on drug-target interactions and build a weighted Drug-Drug Similarity Network according to the drug-drug similarity relationships. Using an energy-model network layout, we generate drug communities associated with specific, dominant drug properties. DrugBank confirms the properties of 59.52% of the drugs in these communities, and 26.98% are existing drug repositioning hints we reconstruct with our DDSN approach. The remaining 13.49% of the drugs seem not to match the dominant pharmacologic property; thus, we consider them potential drug repurposing hints. The resources required to test all these repurposing hints are considerable. Therefore we introduce a mechanism of prioritization based on the betweenness/degree node centrality. Using betweenness/degree as an indicator of drug repurposing potential, we select Azelaic acid and Meprobamate as a possible antineoplastic and antifungal, respectively. Finally, we use a test procedure based on molecular docking to analyze Azelaic acid and Meprobamate's repurposing.

SAS score: Targeting high-specificity for efficient population-wide monitoring of obstructive sleep apnea.

PROPOSAL: This paper investigates a novel screening tool for Obstructive Sleep Apnea Syndrome (OSAS), which aims at efficient population-wide monitoring. To this end, we introduce SASscore which provides better OSAS prediction specificity while maintaining a high sensitivity. METHODS: We process a cohort of 2595 patients from 4 sleep laboratories in Western Romania, by recording over 100 sleep, breathing, and anthropometric measurements per patient; using this data, we compare our SASscore with state of the art scores STOP-Bang and NoSAS through area under curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also evaluate the performance of SASscore by considering different Apnea-Hypopnea Index (AHI) diagnosis cut-off points and show that custom refinements are possible by changing the score's threshold. RESULTS: SASscore takes decimal values within the interval (2, 7) and varies linearly with AHI; it is based on standardized measures for BMI, neck circumference, systolic blood pressure and Epworth score. By applying the STOP-Bang and NoSAS questionnaires, as well as the SASscore on the patient cohort, we respectively obtain the AUC values of 0.69 (95% CI 0.66-0.73, p < 0.001), 0.66 (95% CI 0.63-0.68, p < 0.001), and 0.73 (95% CI 0.71-0.75, p < 0.001), with sensitivities values of 0.968, 0.901, 0.829, and specificity values of 0.149, 0.294, 0.359, respectively. Additionally, we cross-validate our score with a second independent cohort of 231 patients confirming the high specificity and good sensitivity of our score. When raising SASscore's diagnosis cut-off point from 3 to 3.7, both sensitivity and specificity become roughly 0.6. CONCLUSIONS: In comparison with the existing scores, SASscore is a more appropriate screening tool for monitoring large populations, due to its improved specificity. Our score can be tailored to increase either sensitivity or specificity, while balancing the AUC value.

Weighted Betweenness Preferential Attachment: A New Mechanism Explaining Social Network Formation and Evolution.

The dynamics of social networks is a complex process, as there are many factors which contribute to the formation and evolution of social links. While certain real-world properties are captured by the degree-driven preferential attachment model, it still cannot fully explain social network dynamics. Indeed, important properties such as dynamic community formation, link weight evolution, or degree saturation cannot be completely and simultaneously described by state of the art models. In this paper, we explore the distribution of social network parameters and centralities and argue that node degree is not the main attractor of new social links. Consequently, as node betweenness proves to be paramount to attracting new links - as well as strengthening existing links -, we propose the new Weighted Betweenness Preferential Attachment (WBPA) model, which renders quantitatively robust results on realistic network metrics. Moreover, we support our WBPA model with a socio-psychological interpretation, that offers a deeper understanding of the mechanics behind social network dynamics.

Network science meets respiratory medicine for OSAS phenotyping and severity prediction.

Obstructive sleep apnea syndrome (OSAS) is a common clinical condition. The way that OSAS risk factors associate and converge is not a random process. As such, defining OSAS phenotypes fosters personalized patient management and population screening. In this paper, we present a network-based observational, retrospective study on a cohort of 1,371 consecutive OSAS patients and 611 non-OSAS control patients in order to explore the risk factor associations and their correlation with OSAS comorbidities. To this end, we construct the Apnea Patients Network (APN) using patient compatibility relationships according to six objective parameters: age, gender, body mass index (BMI), blood pressure (BP), neck circumference (NC) and the Epworth sleepiness score (ESS). By running targeted network clustering algorithms, we identify eight patient phenotypes and corroborate them with the co-morbidity types. Also, by employing machine learning on the uncovered phenotypes, we derive a classification tree and introduce a computational framework which render the Sleep Apnea Syndrome Score (SASScore); our OSAS score is implemented as an easy-to-use, web-based computer program which requires less than one minute for processing one individual. Our evaluation, performed on a distinct validation database with 231 consecutive patients, reveals that OSAS prediction with SASScore has a significant specificity improvement (an increase of 234%) for only 8.2% sensitivity decrease in comparison with the state-of-the-art score STOP-BANG. The fact that SASScore has bigger specificity makes it appropriate for OSAS screening and risk prediction in big, general populations.

Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing.

Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications.

A high-availability architecture for continuous monitoring of sleep disorders.

We present a complete technical solution for continuously monitoring vital signs required for observing sleep apnoea events, one of the major sleep respiratory disorders. Based on industry accepted medical devices, we developed a GSM-based remote data acquisition and transfer module that is integrated via a set of web services into the server side of the application. The back-end is responsible with aggregating all the data, and, based on machine learning techniques, it provides a first level of filtering in order to warn about possible abnormalities. The proposed solution is currently under the test phase at the "Victor Babes" Hospital in Timisoara, Romania.