Darwin’s Tree of Life is Numbered. Resolving the Origins of Species by Mass

Downard, Kevin M.

doi:10.1007/s11692-020-09517-7

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…68) Beyond the study of viruses, the approach has been demonstrated to have universal versatility to resolve a wide range of organisms across the biological kingdoms of life 75) and among animal species. 76) A mass tree produced from the peptide masses derived from the double digestion (trypsin+GluC) of the surface S-protein of the SARS-CoV2 virus for five major variants is shown in Fig. 7.…”

Section: Charting and Studying Viral Evolution With High-resolution Msmentioning

confidence: 99%

“…23) The mass tree resolves the spike protein (accession UHT20210.1) of one strain from another (accession UID24501. Thus the mass trees [22][23][24]58,[67][68][69][70][71][72][73][74][75][76] not only correctly resolve and display different virus strains of different variants from one another, they also correctly identify (in some 80% of cases) mutations associated with viral evolution without the need for, or alignment of, the protein sequences themselves. This affords time saving and removes a computationally complex step associated with traditional gene or protein-based phylogenetic methods.…”

Section: Charting and Studying Viral Evolution With High-resolution Msmentioning

confidence: 99%

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25 Years Responding to Respiratory and Other Viruses with Mass Spectrometry

Downard

2023

Mass Spectrometry

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This review article presents the development and application of mass spectrometry (MS) approaches, developed in the author’s laboratory over the past 25 years, to detect; characterise, type and subtype; and distinguish major variants and subvariants of respiratory viruses such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All features make use of matrix-assisted laser desorption ionisation (MALDI) mass maps, recorded for individual viral proteins or whole virus digests. A MALDI-based immunoassay in which antibody–peptide complexes were preserved on conventional MALDI targets without their immobilisation led to an approach that enabled their indirect detection. The site of binding, and thus the molecular antigenicity of viruses, could be determined. The same approach was employed to study antivirals bound to their target viral protein, the nature of the binding residues, and relative binding affinities. The benefits of high-resolution MS were exploited to detect sequence-conserved signature peptides of unique mass within whole virus and single protein digests. These enabled viruses to be typed, subtyped, their lineage determined, and variants and subvariants to be distinguished. Their detection using selected ion monitoring improved analytical sensitivity limits to aid the identification of viruses in clinical specimens. The same high-resolution mass map data, for a wide range of viral strains, were input into a purpose-built algorithm (MassTree) in order to both chart and interrogate viral evolution. Without the need for gene or protein sequences, or any sequence alignment, this phylonumerics approach also determines and displays single-point mutations associated with viral protein evolution in a single-tree building step.

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Section: Charting and Studying Viral Evolution With High-resolution Msmentioning

confidence: 99%

Section: Charting and Studying Viral Evolution With High-resolution Msmentioning

confidence: 99%

25 Years Responding to Respiratory and Other Viruses with Mass Spectrometry

Downard

2023

Mass Spectrometry

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“…9,10 The approach has been demonstrated to have universal versatility as a protein phylogeny method for a wide range of organisms across the biological kingdoms of life. 11,12 Mass maps are mass spectral profiles for the peptides generated following the proteolytic digestion of a protein. 13 If two common proteins from different virus strains vary by one or more mutations, the mass maps for each of them will differ for the masses of the peptide segments where those mutations reside.…”

Section: Introductionmentioning

confidence: 99%

“…Mass trees have been found in a series of studies to be highly congruent to sequence based trees and thus reliable indicators of evolution histories and trajectories. Unlike sequence-based trees, no gene or protein sequences are required to be generated or aligned, and the phylonumerics strategy [9][10][11][12]14 is thus less encumbered than a phylogenomics pipeline. 15 Here we investigate its ability to chart and study the evolution of SARS-CoV2 for over 3000 strains of the virus and distinguish major variants of concern on the tree by means of identifying the presence of variant-specific peptide markers.…”

Section: Introductionmentioning

confidence: 99%

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Charting and tracking the evolution of the SARS CoV-2 coronavirus variants of concern with protein mass spectrometry

Hoyle¹,

Mann²,

Akand

et al. 2023

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Sequence‐free Phylogenetics With Mass Spectrometry

Downard

2020

Mass Spectrometry Reviews

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An alternative, more rapid, sequence-free approach to build phylogenetic trees has been conceived and implemented. Molecular phylogenetics has continued to mostly focus on improvement in tree construction based on gene sequence alignments. Here protein-based phylogenies are constructed using numerical data sets ("phylonumerics") representing the masses of peptide segments recorded in a mass mapping experiment. This truly sequence-free method requires no gene sequences, nor their alignment, to build the trees affording a considerable time and cost-saving to conventional phylogenetics methods. The approach also calculates single point amino acid mutations from a comparison of mass pairs from different maps in the data set and displays these at branch nodes across the tree together with their frequency. Studies of the consecutive, and near-consecutive, ancestral and descendant mutations across interconnected branches of a mass tree allow putative adaptive, epistatic, and compensatory mutations to be identified in order to investigate mechanisms associated with evolutionary processes and pathways. A side-by-side comparison of this sequence-free approach and conventional gene sequence phylogenetics is discussed.

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Darwin’s Tree of Life is Numbered. Resolving the Origins of Species by Mass

Cited by 10 publications

References 24 publications

25 Years Responding to Respiratory and Other Viruses with Mass Spectrometry

25 Years Responding to Respiratory and Other Viruses with Mass Spectrometry

Charting and tracking the evolution of the SARS CoV-2 coronavirus variants of concern with protein mass spectrometry

Sequence‐free Phylogenetics With Mass Spectrometry

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