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Abstract The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data. 

Abstract The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data. 

Abstract BackgroundNon-pharmaceutical interventions (NPIs) have been implemented worldwide to curb COVID-19 spread. Belarus is a rare case of a country with a relatively modern healthcare system, where highly limited NPIs have been enacted. Thus, investigation of Belarusian COVID-19 dynamics is essential for the local and global assessment of the impact of NPI strategies. MethodsWe integrate genomic epidemiology and surveillance methods to investigate the spread of SARS-CoV-2 in Belarus in 2020. We utilize phylodynamics, phylogeography, and probabilistic bias inference to study the virus import and export routes, the dynamics of the effective reproduction number, and the incidence of SARS-CoV-2 infection. ResultsHere we show that the estimated cumulative number of infections by June 2020 exceeds the confirmed case number by a factor of ~4 (95% confidence interval (2; 9)). Intra-country SARS-CoV-2 genomic diversity originates from at least 18 introductions from different regions, with a high proportion of regional transmissions. Phylodynamic analysis indicates a moderate reduction of the effective reproductive number after the introduction of limited NPIs, but its magnitude is lower than for developed countries with large-scale NPIs. On the other hand, the effective reproduction number estimate is comparable with that for the neighboring Ukraine, where NPIs were broader. ConclusionsThe example of Belarus demonstrates how countries with relatively low outward population mobility continue to be integral parts of the global epidemiological environment. Comparison of the effective reproduction number dynamics for Belarus and other countries reveals the effect of different NPI strategies but also emphasizes the role of regional Eastern European sociodemographic factors in the virus spread. 

Abstract In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020–2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortalityP-score metrics were also compared with the neighboring countries. In summary, there were three “waves” of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new “wave” of the all-cause mortality was higher than the previous one and the mortality “peaks” corresponded in time to three “waves” of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic. 

The integration of viral genomic data into public health surveillance has revolutionized our ability to track and forecast infectious disease dynamics. This review addresses two critical aspects of infectious disease forecasting and monitoring: the methodological workflow for epidemic forecasting and the transformative role of molecular surveillance. We first present a detailed approach for validating epidemic models, emphasizing an iterative workflow that utilizes ordinary differential equation (ODE)-based models to investigate and forecast disease dynamics. We recommend a more structured approach to model validation, systematically addressing key stages such as model calibration, assessment of structural and practical parameter identifiability, and effective uncertainty propagation in forecasts. Furthermore, we underscore the importance of incorporating multiple data streams by applying both simulated and real epidemiological data from the COVID-19 pandemic to produce more reliable forecasts with quantified uncertainty. Additionally, we emphasize the pivotal role of viral genomic data in tracking transmission dynamics and pathogen evolution. By leveraging advanced computational tools such as Bayesian phylogenetics and phylodynamics, researchers can more accurately estimate transmission clusters and reconstruct outbreak histories, thereby improving data-driven modeling and forecasting and informing targeted public health interventions. Finally, we discuss the transformative potential of integrating molecular epidemiology with mathematical modeling to complement and enhance epidemic forecasting and optimize public health strategies. 

Over the past two decades, the study of self-similarity and fractality in discrete structures, particularly complex networks, has gained momentum. This surge of interest is fueled by the theoretical developments within the theory of complex networks and the practical demands of real-world applications. Nonetheless, translating the principles of fractal geometry from the domain of general topology, dealing with continuous or infinite objects, to finite structures in a mathematically rigorous way poses a formidable challenge. In this paper, we overview such a theory that allows to identify and analyze fractal networks through the innate methodologies of graph theory and combinatorics. It establishes the direct graph-theoretical analogs of topological (Lebesgue) and fractal (Hausdorff) dimensions in a way that naturally links them to combinatorial parameters that have been studied within the realm of graph theory for decades. This allows to demonstrate that the self-similarity in networks is defined by the patterns of intersection among densely connected network communities. Moreover, the theory bridges discrete and continuous definitions by demonstrating how the combinatorial characterization of Lebesgue dimension via graph representation by its subsets (subgraphs/communities) extends to general topological spaces. Using this framework, we rigorously define fractal networks and connect their properties with established combinatorial concepts, such as graph colorings and descriptive complexity. The theoretical framework surveyed here sets a foundation for applications to real-life networks and future studies of fractal characteristics of complex networks using combinatorial methods and algorithms. 

Phage display technique has a multitude of applications such as epitope mapping, organ targeting, therapeutic antibody engineering and vaccine design. One area of particular importance is the detection of cancers in early stages, where the discovery of binding motifs and epitopes is critical. While several techniques exist to characterize phages, Next Generation Sequencing (NGS) stands out for its ability to provide detailed insights into antibody binding sites on antigens. However, when dealing with NGS data, identifying regulatory motifs poses significant challenges. Existing methods often lack scalability for large datasets, rely on prior knowledge about the number of motifs, and exhibit low accuracy. In this paper, we present a novel approach for identifying regulatory motifs in NGS data. Our method leverages results from graph theory to overcome the limitations of existing techniques.