Assessing phylogenetic confidence at pandemic scales.

Area of Science:

• Evolutionary Biology
• Genomic Epidemiology
• Computational Biology

Background:

• Phylogenetic confidence assessment is vital in evolutionary biology and genomic epidemiology.
• Existing methods like bootstrap lack efficiency for large datasets and can be difficult to interpret.
• Current methods focus on clade membership, limiting their application in epidemiological contexts.

Purpose of the Study:

• To introduce Subtree Pruning and Regrafting-based Tree Assessment (SPRTA) as an efficient and interpretable method for phylogenetic confidence.
• To shift phylogenetic support measurement from clade membership to evolutionary histories and lineage placement.
• To enable pandemic-scale probabilistic assessment of transmission and mutational histories.

Main Methods:

• Development and application of Subtree Pruning and Regrafting-based Tree Assessment (SPRTA).
• Analysis of a global SARS-CoV-2 phylogenetic tree comprising over two million genomes.
• Evaluation of phylogenetic uncertainty's impact on inferred mutation rates and lineage classification.

Main Results:

• SPRTA provides an efficient and interpretable approach to assess phylogenetic confidence.
• Identified plausible alternative evolutionary origins for SARS-CoV-2 variants.
• Demonstrated the effect of phylogenetic uncertainty on mutation rate inference and Pango lineage classification reliability.

Conclusions:

• SPRTA enables detailed, pandemic-scale probabilistic assessment of transmission and mutational histories.
• The method enhances interpretability of large-scale phylogenetic analyses.
• SPRTA improves preparedness and response capabilities for future pandemics.