The Omicron XBB.1 Variant and Its Descendants: Genomic Mutations, Rapid Dissemination and Notable Characteristics.

The SARS-CoV-2 virus, which is a major threat to human health, has undergone many mutations during the replication process due to errors in the replication steps and modifications in the structure of viral proteins. The XBB variant was identified for the first time in Singapore in the fall of 2022. It was then detected in other countries, including the United States, Canada, and the United Kingdom. We study the impact of sequence changes on spike protein structure on the subvariants of XBB, with particular attention to the velocity of variant diffusion and virus activity with respect to its diffusion. We examine the structural and functional distinctions of the variants in three different conformations: (i) spike glycoprotein in complex with ACE2 (1-up state), (ii) spike glycoprotein (closed-1 state), and (iii) S protein (open-1 state). We also estimate the affinity binding between the spike protein and ACE2. The market binding affinity observed in specific variants raises questions about the efficacy of current vaccines in preparing the immune system for virus variant recognition. This work may be useful in devising strategies to manage the ongoing COVID-19 pandemic. To stay ahead of the virus evolution, further research and surveillance should be carried out to adjust public health measures accordingly.

SARS-CoV-2 protein structure and sequence mutations: Evolutionary analysis and effects on virus variants.

The structure and sequence of proteins strongly influence their biological functions. New models and algorithms can help researchers in understanding how the evolution of sequences and structures is related to changes in functions. Recently, studies of SARS-CoV-2 Spike (S) protein structures have been performed to predict binding receptors and infection activity in COVID-19, hence the scientific interest in the effects of virus mutations due to sequence, structure and vaccination arises. However, there is the need for models and tools to study the links between the evolution of S protein sequence, structure and functions, and virus transmissibility and the effects of vaccination. As studies on S protein have been generated a large amount of relevant information, we propose in this work to use Protein Contact Networks (PCNs) to relate protein structures with biological properties by means of network topology properties. Topological properties are used to compare the structural changes with sequence changes. We find that both node centrality and community extraction analysis can be used to relate protein stability and functionality with sequence mutations. Starting from this we compare structural evolution to sequence changes and study mutations from a temporal perspective focusing on virus variants. Finally by applying our model to the Omicron variant we report a timeline correlation between Omicron and the vaccination campaign.

GTExVisualizer: a web platform for supporting ageing studies.

MOTIVATION: Studying ageing effects on molecules is an important new topic for life science. To perform such studies, the need for data, models, algorithms, and tools arises to elucidate molecular mechanisms. GTEx (standing for Genotype-Tissue Expression) portal is a web-based data source allowing to retrieve patients' transcriptomics data annotated with tissues, gender, and age information. It represents the more complete data sources for ageing effects studies. Nevertheless, it lacks functionalities to query data at the sex/age level, as well as tools for protein interaction studies, thereby limiting ageing studies. As a result, users need to download query results to proceed to further analysis, such as retrieving the expression of a given gene on different age (or sex) classes in many tissues. RESULTS: We present the GTExVisualizer, a platform to query and analyse GTEx data. This tool contains a web interface able to: (i) graphically represent and study query results; (ii) analyse genes using sex/age expression patterns, also integrated with network-based modules; and (iii) report results as plot-based representation as well as (gene) networks. Finally, it allows the user to obtain basic statistics which evidence differences in gene expression among sex/age groups. CONCLUSION: The GTExVisualizer novelty consists in providing a tool for studying ageing/sex-related effects on molecular processes. AVAILABILITY AND IMPLEMENTATION: GTExVisualizer is available at: http://gtexvisualizer.herokuapp.com. The source code and data are available at: https://github.com/UgoLomoio/gtex_visualizer.

Computational analysis of the sequence-structure relation in SARS-CoV-2 spike protein using protein contact networks.

The structure of proteins impacts directly on the function they perform. Mutations in the primary sequence can provoke structural changes with consequent modification of functional properties. SARS-CoV-2 proteins have been extensively studied during the pandemic. This wide dataset, related to sequence and structure, has enabled joint sequence-structure analysis. In this work, we focus on the SARS-CoV-2 S (Spike) protein and the relations between sequence mutations and structure variations, in order to shed light on the structural changes stemming from the position of mutated amino acid residues in three different SARS-CoV-2 strains. We propose the use of protein contact network (PCN) formalism to: (i) obtain a global metric space and compare various molecular entities, (ii) give a structural explanation of the observed phenotype, and (iii) provide context dependent descriptors of single mutations. PCNs have been used to compare sequence and structure of the Alpha, Delta, and Omicron SARS-CoV-2 variants, and we found that omicron has a unique mutational pattern leading to different structural consequences from mutations of other strains. The non-random distribution of changes in network centrality along the chain has allowed to shed light on the structural (and functional) consequences of mutations.

Structural analysis of SARS-CoV-2 Spike protein variants through graph embedding.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected almost all countries. The unprecedented spreading of this virus has led to the insurgence of many variants that impact protein sequence and structure that need continuous monitoring and analysis of the sequences to understand the genetic evolution and to prevent possible dangerous outcomes. Some variants causing the modification of the structure of the proteins, such as the Spike protein S, need to be monitored. Protein contact networks (PCNs) have been recently proposed as a modelling framework for protein structures. In such a framework, the protein structure is represented as an unweighted graph whose nodes are the central atoms of the backbones (C- α ), and edges connect two atoms falling in the spatial distance between 4 and 7 Å. PCN may also be a data-rich representation since we may add to each node/atom biological and topological information. Such formalism enables the possibility of using algorithms from graph theory to analyze the graph. In particular, we refer to graph embedding methods enabling the analysis of such graphs with deep learning methods. In this work, we explore the possibility of embedding PCN using Graph Neural Networks and then analyze in the embedded space each residue to distinguish mutated residues from non-mutated ones. In particular, we analyzed the structure of the Spike protein of the coronavirus. First, we obtained the PCNs of the Spike protein for the wild-type, α , ß , and δ variants. Then we used the GraphSage embedding algorithm to obtain an unsupervised embedding. Then we analyzed the point of mutation in the embedded space. Results show the characteristics of the mutation point in the embedding space.