Biology subjects

Mojsiejczuk, L.

Publications and source records attributed to Mojsiejczuk, L..

5 recordsLinked to original sources

bioRxiv2026

Flu Mutation Explorer: an Interactive Platform for Mapping Host Adaptation Mutations in Influenza A Viruses

A rapid expansion of influenza A virus (IAV) genome sequencing has transformed global surveillance but has also created major challenges for interpreting the biological significance of viral mutations, particularly amino acid replacements associated with host adaptation. Resources have been created to support mutation annotation and phylogenetic analysis, but there is a need for a tool that integrates experimentally derived phenotypic evidence with evolutionary context in a framework suitable for users without prior training in bioinformatics. Here, we present the Flu Mutation Explorer, an interactive web application that combines large-scale influenza phylogenies with a manually curated database of reported mammalian adaptation mutations, to enable the exploration and interpretation of IAV genetic variation. The underlying database comprises over 1.5 million publicly available IAV sequences and over 1000 mutations associated with mammalian adaptation. The Flu Mutation Explorer enables users to query protein sequences, visualise amino acid distributions across viral lineages, examine host-specific conservation patterns, and identify adaptation mutation with links to supporting literature. We include case studies which demonstrate the platforms use in assessing amino acid conservation at sites of interest and in rapidly identifying candidate mammalian adaptation mutations during the ongoing H5N1 panzootic. By integrating genomic, phylogenetic, and functional information into an intuitive interface, the Flu Mutation Explorer lowers the barriers to interpreting influenza sequences for specialists and non-specialists alike.

microbiology↗

bioRxiv2026

Protein language models learn underlying mutation biases alongside fitness landscapes

Protein language models (PLMs) score the effects of amino acid replacements as pseudo-probabilities, which are widely utilised to map protein fitness landscapes. However, because their training data relies on natural amino acid sequences, these models conflate protein structural constraints with nucleotide mutation biases and codon accessibility. Using the rapid emergence of the divergent influenza A H3N2 K lineage as a stress test, we investigate how base PLMs (ESM-2 and ESM-C) versus fine-tuned versions of these models capture mutational processes. We systematically implement a parameter sweep to explicitly couple (or decouple) empirical nucleotide mutational supply from PLM-assessed amino acid substitution pseudo-probabilities across evolutionary forecasting tasks. We find that base PLMs implicitly learn generic nucleotide-level mutational constraints, an effect strongly amplified by virus-specific fine-tuning. Incorporating explicit mutational accessibility significantly improves the binary prediction of observed amino acid changes. Conversely, when predicting the final circulating frequency of variants that have already emerged, adding mutational supply degrades performance, confirming that selection dominates post-emergence dynamics. Additionally, we perform amino-acid-level epistatic scanning to investigate protein structural constraints in the context of genetic background. This indicates the improbable antigenic substitution I160K is dependent on co-occurring S144N and N158D mutations in the H3N2 K lineage. Ultimately, current PLM pseudo-probabilities are a composite metric that conflates protein structural fitness with historical biases in mutational supply. Explicitly decoupling these independent evolutionary processes optimises predictive accuracy for real-world pathogen forecasting and isolates pure protein fitness for synthetic design pipelines.

evolutionary biology↗

bioRxiv2026

Understanding the emergence of the influenza A/H3N2 K subclade in its historical and evolutionary context

The emergence in 2025/26 of the influenza A/H3N2 K substrain (H3N2/K) was the cause of significant public health concern. This genetically divergent virus was assessed to have a strongly decreased reactivity to contemporary vaccine strains. Respectively prolonged and early influenza seasons in the Southern and Northern Hemispheres contributed to concerns about vaccine efficacy. Here we retrospectively assessed the genetic and antigenic properties of this virus, combining epidemiological surveillance data, computational antigenic analysis, and serological data using samples from a well-stratified UK cohort. In contrast to initial indications, we found that despite the genetic distinctiveness of H3N2/K the virus had undergone limited antigenic change, suggesting that its emergence was instead the result of selection for non-antigenic properties. We confirmed previous results showing that contemporary vaccines produced an enhanced neutralising response to H3N2/K but, in a stratified serological analysis, showed that responses to the J and K substrains were age-dependent, largely driven by patterns of vaccination. Our results have implications for antigenic surveillance and for public communication strategies in future influenza seasons.

evolutionary biology↗

bioRxiv2024

POLYGENIC DETERMINANTS OF H5N1 ADAPTATION TO BOVINE CELLS

Avian influenza H5N1 clade 2.3.4.4b viruses caused a global panzootic and, unexpectedly, widespread outbreaks in dairy cattle, therefore representing a pandemic threat. To inform effective control strategies, it is critical to determine whether the potential to adapt to bovine cells is a generalised feature of H5N1 viruses, or is specific to clade 2.3.4.4b, or even more restricted to specific genotypes within this clade (e.g., B3.13 and D1.1). Using a large panel of H5N1 viruses representing >60 years of their natural history and other IAV for comparative purposes, we demonstrate that virus adaptation to bovine cells is: (i) highly variable across 2.3.4.4b genotypes, (ii) limited in viruses predating the global expansion of this clade, (iii) determined by the viral internal gene cassette, and (iv) not restricted to udder epithelial cells. Mutations in the PB2 polymerase subunit, particularly M631L, emerge as key determinants of adaptation, although their phenotypic effects are context dependent and have limited enhanced viral polymerase activity in human cells. Bovine B3.13 and some avian genotypes also exhibit enhanced modulation of bovine interferon-induced antiviral responses, determined by at least the viral PB2, nucleoprotein, and the non-structural protein NS1. Our results highlight the polygenic nature of IAV host range and reveal that the potential to cross the species barrier varies during the evolutionary trajectory of H5N1, with some avian viruses more predisposed to spillover than others.

microbiology↗

bioRxiv2020

THE ORIGIN OF A NEW HUMAN VIRUS: PHYLOGENETIC ANALYSIS OF THE EVOLUTION OF SARS-COV-2

During the first months of SARS-CoV-2 evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS-CoV-2. The molecular evolution in nine genomic regions of SARS-CoV-2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence. All observed phylogenetic signals were very low and trees topologies were in agreement with those signals. However, after four months of evolution, it was possible to identify regions revealing an incipient viral lineages formation despite the low phylogenetic signal, since fortnight 3. Finally, the SARS-CoV-2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated to values of 1.37 x 10-3 and 2.19 x 10-3 substitution/site/year, respectively. In conclusion, results obtained in this work about the variable diversity of crucial viral regions and the determination of the evolutionary rate are consequently decisive to understand essential feature of viral emergence. In turn, findings may allow characterizing for the first time, the evolutionary rate of S protein that is crucial for vaccines development.

evolutionary biology↗