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Biology subjects

Herzig, J. C.

Publications and source records attributed to Herzig, J. C..

2 recordsLinked to original sources

Phylogenies as graphs: structured neural networks improve host origin predictions from paramyxovirus sequences

Accurately identifying the host of a virus from its genome sequence is a task with important applications in zoonotic disease surveillance and filling data gaps for metagenomic sampling. Machine learning approaches have seen broad application in making host predictions directly from viral genome sequences. However, most host prediction models do not incorporate information on viral phylogeny, which is strongly correlated with both genome composition and host. We apply a novel graph neural network (GNN) approach which explicitly represents viral phylogeny in model architecture to predict hosts of origin within the paramyxoviruses. We conduct rigorous benchmarking against non-structured neural networks and predictions made using phylogeny alone, showing that GNNs carry distinct advantages over other methods when making predictions where training data is sparse. Validation across different phylogenetic scales shows that simple phylogenetic prediction is effective in many applications and that phylogeny contributes a large proportion of the predictive power of host prediction models, with genome compositional features providing additional power only for specific predictions outside the range of the training data. This novel modelling approach and model validation framework are flexible and can be applied to other viral families.

evolutionary biology↗

Structural constraints acting on the SARS-CoV-2 spike protein reveal limited space for viral adaptation

The SARS-CoV-2 pandemic resulted in an unprecedented scientific response. The enormous scale of global genome sequencing, protein structural determination and targeted studies of protein and variant dynamics has resulted in a unique dataset which provides a valuable resource for understanding of viral evolutionary dynamics. Previous analysis of SARS-CoV-2 evolution has revealed apparently saltatory dynamics, with viral variants arising following large evolutionary jumps without genetic intermediates represented in the sequence database. We utilise rich SARS-CoV-2 datasets to interrogate the role of protein structural constraint in SARS-CoV-2 evolution and whether these evolutionary jumps may result from the viral spike protein accessing new regions of viable sequence space. We apply multiple computational predictors of structural constraint across different structural backgrounds and assess how constraint has changed during SARS-CoV-2 variant evolution. These predictions are validated using substitution data from the SARS-CoV-2 global sequence database. We find that all predictive methods suggest that the structural constraint experienced by specific sites has undergone very limited change, despite significant phenotypic evolution of the SARS-CoV-2 S protein. Signature mutations for variants of concern are not found to be under structural constraint by any computational predictor regardless of which viral variant structure is used to calculate predictions. We also develop a machine learning model to assess substitution viability, combining predictors of evolutionary constraint with information about local structural context. This confirms our conclusions, with model performance largely unaffected by the use of different viral variant structures. We also find no reduction in the shared proportion of accessible substitutions over evolutionary time, as would be expected if the S protein had entered and explored novel sequence space during variant evolution. These results suggest that despite its rapid rate of mutation, the SARS-CoV-2 S protein is subject to strict structural constraints and shows that viral genomes exhibit limited plasticity following infection of a new host.

evolutionary biology↗