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Simple Summary: As COVID-19 shifts from pandemic to endemic, emerging variants may be more or less virulent. Predicting whether an emerging COVID-19 variant has of high risk of causing severe disease is needed to plan for potential burdens on hospital capacity and protecting vulnerable populations. However, it takes time to do laboratory and animal experiments to determine whether a new genetic variant might be more severe, and the results may not be representative of when the virus infects humans. By the time there is epidemiological data on the severity of disease associated with a new variant, it can be too late for designing an optimal public health response. There is a critical need for computer models that can predict severe disease risk from genetic sequence data, which can be obtained from just the first few infections in a potential incoming wave. Two key challenges make computer modeling difficult: (1) sequence changes are complex, and (2) using historical data to predict future disease requires accounting for the confounding effects of changing patient demographics, improving therapeutics, and increased vaccination. In this paper, we introduce a novel interpretable deep learning architecture to solve this problem, demonstrating that it can make robust predictions for emerging variants. Through the COVID-19 pandemic, SARS-CoV-2 has gained and lost multiple mutations in novel or unexpected combinations. Predicting how complex mutations affect COVID-19 disease severity is critical in planning public health responses as the virus continues to evolve. This paper presents a novel computational framework to complement conventional lineage classification and applies it to predict the severe disease potential of viral genetic variation. The transformer-based neural network model architecture has additional layers that provide sample embeddings and sequence-wide attention for interpretation and visualization. First, training a model to predict SARS-CoV-2 taxonomy validates the architecture's interpretability. Second, an interpretable predictive model of disease severity is trained on spike protein sequence and patient metadata from GISAID. Confounding effects of changing patient demographics, increasing vaccination rates, and improving treatment over time are addressed by including demographics and case date as independent input to the neural network model. The resulting model can be interpreted to identify potentially significant virus mutations and proves to be a robust predctive tool. Although trained on sequence data obtained entirely before the availability of empirical data for Omicron, the model can predict the Omicron's reduced risk of severe disease, in accord with epidemiological and experimental data. [ABSTRACT FROM AUTHOR]

Currently, as an effect of the COVID-19 pandemic, bioinformatics, genomics, and biological computations are gaining increased attention. Genomes of viruses can be represented by character strings based on their nucleobases. Document similarity metrics can be applied to these strings to measure their similarities. Clustering algorithms can be applied to the results of their document similarities to cluster them. P systems or membrane systems are computation models inspired by the flow of information in the membrane cells. These can be used for various purposes, one of them being data clustering. This paper studies a novel and versatile clustering method for genomes and the utilization of such membrane clustering models using document similarity metrics, which is not yet a well-studied use of membrane clustering models. [ABSTRACT FROM AUTHOR]

Advantageous variants of the SARS-CoV-2 virus have arisen through mutations, particularly on a single amino acid basis. These point mutations can cause changes in the structure of SARS-CoV-2 and affect the efficiency of interaction with the ACE2 protein. N501Y and E484K mutations affecting binding by ACE2 have been widely observed. This study aimed to predict SARS-CoV-2 mutations that could be as effective as N501Y and E484K and pose a danger due to their high contagiousness. Experimental data on SARS-CoV-2 and ACE2 binding and stability were associated with different amino acid properties and integrated into machine learning and computational biology techniques. As a result of the analyses made in algorithms, N501M, Q414A, N354K, Q498H and N460K have been predicted to be likely to have a dangerous effect. The N501W mutations are most likely to have dangerous effects on the spread of the coronavirus. We suggest that attention should be paid to the position 501 mutation since this position is repeated in the lists of mutations that the algorithm detected as dangerous. G446, G447, Y505, T500, Q493, Y473, and G476 were determined as the positions where dangerous variants could be seen as a result of the analyses of the multiple interaction data created with the ACE2 and RBD interaction data. The 13 dangerous positions and mutations have been detected to accurately describe the position of the mutations caused by the Omicron variant and were among the known dangerous mutations similar to those occurring at Q498, G446, Y505 and Q493 positions. [ABSTRACT FROM AUTHOR]

According to various estimates, only a small percentage of existing viruses have been discovered, naturally much less being represented in the genomic databases. High-throughput sequencing technologies develop rapidly, empowering large-scale screening of various biological samples for the presence of pathogen-associated nucleotide sequences, but many organisms are yet to be attributed specific loci for identification. This problem particularly impedes viral screening, due to vast heterogeneity in viral genomes. In this paper, we present a new bioinformatic pipeline, VirIdAl, for detecting and identifying viral pathogens in sequencing data. We also demonstrate the utility of the new software by applying it to viral screening of the feces of bats collected in the Moscow region, which revealed a significant variety of viruses associated with bats, insects, plants, and protozoa. The presence of alpha and beta coronavirus reads, including the MERS-like bat virus, deserves a special mention, as it once again indicates that bats are indeed reservoirs for many viral pathogens. In addition, it was shown that alignment-based methods were unable to identify the taxon for a large proportion of reads, and we additionally applied other approaches, showing that they can further reveal the presence of viral agents in sequencing data. However, the incompleteness of viral databases remains a significant problem in the studies of viral diversity, and therefore necessitates the use of combined approaches, including those based on machine learning methods. [ABSTRACT FROM AUTHOR]

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus. [ABSTRACT FROM AUTHOR]

Significant efforts are being made in many countries around the world to respond to the COVID-19 pandemic by developing diagnostic reagent kits, identifying infected people, determining treatment methods, and finally producing effective vaccines. However, novel coronavirus variants may potentially reduce the effectiveness of all these efforts, demonstrating increased transmissibility and abated response to therapy or vaccines, as well as the possibility of false negative results in diagnostic procedures based on nucleic acid amplification methods. Since the end of 2020, several variants of concern have been discovered around the world. When information about a new, potentially more dangerous strain of pathogen appears, it is crucial to determine the moment of its emergence in a region. Eventually, that permits taking timely measures and minimizing new risks associated with the spreading of the virus. Therefore, numerous nations have made tremendous efforts to identify and trace these virus variants, which necessitates serious technological processes to sequence a large number of viral genomes. Here, we report on our experience as one of the primary laboratories involved in monitoring SARS-CoV-2 variants in Russia. We discuss the various approaches used, describe effective protocols, and outline a potential technique combining several methods to increase the ability to trace genetic variants while minimizing financial and labor costs. [ABSTRACT FROM AUTHOR]