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Alfonsi, T.

Publications and source records attributed to Alfonsi, T..

5 recordsLinked to original sources

Distinctive viral genome signatures are linked to repeated mammalian spillovers of H5N1 in North America

Highly pathogenic avian influenza H5N1 rarely infects mammals. In 2024-2025, however, genotypes B3.13 and D1.1 caused two independent spillovers into U.S. dairy cattle. By analysing 26,930 complete H5N1 genomes from global surveillance, we identified 73 major viral groups, most of which show continent-specific distribution in Europe, Asia, Africa, and North America. North American viruses exhibit higher genetic diversity in specific viral segments, including variants potentially associated with mammalian adaptation. Both dairy-cattle-associated B3.13 and D1.1 genotypes originate from the same geographic macro-area, suggesting a possible regional hotspot where avian-mammalian interfaces may facilitate viral adaptation. Our findings place the U.S. outbreaks in a global framework and indicate that North American H5N1 may be predisposed to cross-species transmission. TeaserComparative genomics and geographic analyses delineate distinctive genomic features of H5N1 genotypes associated with U.S. dairy cattle spillover.

evolutionary biology↗

Multi-scale early warning system for influenza A spillovers

Spillovers of Influenza A viruses into farmed animals and humans have the potential to trigger epidemics or even global pandemics. We introduce FluWarning, a highly efficient and elegant computational method based on anomaly detection of codon bias and dinucleotide composition for early flagging of divergent viral HA segments. Applied to H1N1 specimens collected between 2008-2009, FluWarning accurately identifies the emergence of pdm09 - the virus that caused the 2009 flu pandemic; warnings precede the observed progression of the pandemic. Applied to H5N1 specimens collected between 2019 and 2025, FluWarning flagged the emergence of the B3.13 genotype, linked to a spillover event in dairy cows in the United States. In summary, FluWarning is an effective multi-scale warning system for IAVs, detecting spillovers with few available sequences. One-Sentence SummaryEarly detection of zoonoses using a few viral sequences is critical for the timely implementation of mitigation strategies.

bioinformatics↗

ConvMut: A Web tool to analyze viral convergent mutations along phylogenies

Convergent evolution in protein antigens is common across pathogens and has also been documented in SARS-CoV-2 (hCoV-19); the most likely reason is the need to evade the selective pressure exerted by previous infection- or vaccine-elicited immunity. There is a pressing need for tools that allow automated analysis of convergent mutations. In response to this need, we developed ConvMut, a tool to analyze genetic sequence data to identify patterns of recurrent mutations in SARS-CoV-2 evolution. To this end, we exploited the granular phylogenetic tree representation developed by PANGO, allowing us to observe what we call deltas, i.e., groups of mutations that are acquired on top of the immediately upstream tree nodes. Deltas comprise amino acid substitutions, insertions, and deletions. ConvMut can perform individual protein analysis to identify the most common single mutations acquired independently in a given subtree (starting from a user-selected root). Such mutations are represented in a barplot that can be sorted by frequency or position, and filtered by region of interest. Lineages are then gathered into clusters according to their sets of shared mutations. Finally, an interactive graph orders the evolutionary steps of clusters, details the acquired amino acid changes for each sublineage, and allows us to trace the evolutionary path until a selected lineage. Other unique tools are paired with the main functionality of ConvMut to support a complete analysis, such as a frequency analysis for a given nucleotide or amino acid changes at a given residue across a selected phylogenetic subtree. ConvMut will facilitate the design of antiviral anti-Spike monoclonal antibodies and Spike-based vaccines with longer-lasting efficacy, minimizing development and marketing failures.

bioinformatics↗

Data-driven recombination detection in viral genomes

Recombination is a key molecular mechanism for the evolution and adaptation of viruses. The first recombinant SARS-CoV-2 genomes were recognized in 2021; as of today, more than ninety SARS-CoV-2 lineages are designated as recombinant. In the wake of the COVID-19 pandemic, several methods for detecting recombination in SARS-CoV-2 have been proposed; however, none could faithfully confirm manual analyses by experts in the field. We hereby present RecombinHunt, a novel, automated method for the identification of recombinant/mosaic genomes purely based on a data-driven approach. RecombinHunt compares favorably with other state-of-the-art methods and recognizes recombinant SARS-CoV-2 genomes (or lineages) with one or two breakpoints with high accuracy, within reduced turn-around times and small discrepancies with respect to the expert manually-curated standard nomenclature. Strikingly, applied to the complete collection of viral sequences from the recent monkeypox epidemic, RecombinHunt identifies recombinant viral genomes in high concordance with manually curated analyses by experts, suggesting that our approach is robust and can be applied to any epidemic/pandemic virus. In conclusion, RecombinHunt represents a breakthrough in the detection of recombinant viral lineages in pandemic/epidemic scenarios and could substantially improve/advance community-based approaches for the detection of recombinant viral genomes based on phylogenetic analyses.

bioinformatics↗

ViruSurf: an integrated database to investigate viral sequences

ViruSurf, available at http://gmql.eu/virusurf/, is a large public database of viral sequences and integrated and curated metadata from heterogeneous sources (GenBank, COG-UK and NMDC); it also exposes computed nucleotide and amino acid variants, called from original sequences. A GISAID-specific ViruSurf database, available at http://gmql.eu/virusurf_gisaid/, offers a subset of these functionalities. Given the current pandemic outbreak, SARS-CoV-2 data are collected from the four sources; but ViruSurf contains other virus species harmful to humans, including SARS-CoV, MERS-CoV, Ebola, and Dengue. The database is centered on sequences, described from their biological, technological, and organizational dimensions. In addition, the analytical dimension characterizes the sequence in terms of its annotations and variants. The web interface enables expressing complex search queries in a simple way; arbitrary search queries can freely combine conditions on attributes from the four dimensions, extracting the resulting sequences. Several example queries on the database confirm and possibly improve results from recent research papers; results can be recomputed over time and upon selected populations. Effective search over large and curated sequence data may enable faster responses to future threats that could arise from new viruses.

genomics↗