Mass trees [1] represent a new phylogenetic approach with which to chart the evolutionary history of microorganisms without the need for either gene or protein sequence data. They have been shown to be congruent with conventional sequence based trees and can be constructed from mass map data that can more rapidly be acquired by mass spectrometry than PCR based gene sequencing. This offers a particular benefit in terms of microorganisms, such as the influenza virus, that have segmented genomes and thus genes with different evolutionary histories. The time required to conduct full-length gene sequencing across a range of genes for a large number of strains in circulation has restricted the application of PCR methods to the surveillance of only a limited number of strains, as few as 1 in 10000.
We have applied mass trees to trace the evolution of the influenza virus from the perspective of influenza hemagglutinin in human strains [1]. Here we demonstrate their application to study the evolution of influenza N1 and N2 neuraminidase within both human influenza viruses and across all subtypes (N1-N9) in human and animal hosts and, importantly, distinguish antiviral resistant from sensitive strains.
The fitting of experimental mass map data onto such mass trees is also shown to be able to establish strain susceptibility to antiviral inhibitors that target influenza neuraminidase. Furthermore, we demonstrate the trees cluster antiviral resistant strains that contain compensatory mutations in influenza hemagglutinin in a common manner.
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