SARS-CoV-2 Delta and Omicron community transmission networks as added value to contact tracing.

Objectives: Calculations of SARS-CoV-2 transmission networks at a population level have been limited. Networks that estimate infections between individuals and whether this results in a mutation, can be a way to evaluate fitness of a mutational clone by how much it expands in number as well as determining the likelihood a transmission results in a new variant.

Methods: Australian Delta and Omicron SARS-CoV-2 sequences were downloaded from GISAID.

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

The evolution of the SARS-CoV2 coronavirus spike S-protein is studied using a mass spectrometry based protein phylogenetic approach. A study of a large dataset comprising sets of peptide masses derived from over 3000 proteins of the SARS-CoV2 virus shows that the approach is capable of resolving and correctly displaying the evolution of the major variants of concern. Using these numerical datasets, through a pairwise comparison of sets of proteolytic peptide masses for each protein, the tree is built without the need for the sequence data itself or any sequence alignment.

Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission.

Hepatitis E virus (HEV) usually causes self-limited liver diseases but can also result in severe cases. Genotypes 1 (G1) and 2 circulate in developing countries are human-restricted and waterborne, while zoonotic G3 and G4 circulating in industrialized countries preferentially infect human through consumption of contaminated meat. Our aims were to identify amino acid patterns in HEV variants that could be involved in pathogenicity or in transmission modes, related to their impact on antigenicity and viral surface hydrophobicity.

NGlyAlign: an automated library building tool to align highly divergent HIV envelope sequences.

Background: The high variability in envelope regions of some viruses such as HIV allow the virus to establish infection and to escape subsequent immune surveillance. This variability, as well as increasing incorporation of N-linked glycosylation sites, is fundamental to this evasion. It also creates difficulties for multiple sequence alignment methods (MSA) that provide the first step in their analysis.

Mutational networks of escape from transmitted HIV-1 infection.

Human immunodeficiency virus (HIV) is subject to immune selective pressure soon after it establishes infection at the founder stage. As an individual progresses from the founder to chronic stage of infection, immune pressure forces a history of mutations that are embedded in envelope sequences. Determining this pathway of coevolving mutations can assist in understanding what is different with the founder virus and the essential pathways it takes to maintain infection.

Mechanisms of antiviral resistance in influenza neuraminidase revealed by a mass spectrometry based phylonumerics approach.

A mass based phylonumerics approach is shown to be able to investigate the origins of the emergence of antiviral resistance mutations in influenza neuraminidase through a global view of mutational trends. Frequent ancestral and descendant mutations that precede and follow the manifestation of antiviral resistance mutations are identified in N2 neuraminidase. The majority occur in the head region around the active site and drive hydrophilicity changes, primarily through the incorporation or loss of hydroxyl groups.

Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach.

Implementation of a new phylonumerics approach to construct a mass tree representing over 6000 H1N1 human influenza strains has enabled ancestral and compensatory descendant mutations to be identified in N1 neuraminidase that promote antiviral resistance and restore viral fitness. Adjacent to the H275Y resistance mutation site, mutations S299A and S247N, respectively, lead the evolution of oseltamivir-resistant strains and restore viral fitness to those strains thereafter. Importantly the mass tree phylonumerics approach can identify such mutations globally, without any positional bias, so that functionally linked or compensatory mutations remote in the sequence or structure of the protein can be identified and interrogated.

Identification of epistatic mutations and insights into the evolution of the influenza virus using a mass-based protein phylogenetic approach.

A mass-based protein phylogenetic approach developed in this laboratory has been applied to study mutation trends and identify consecutive or near-consecutive mutations typically associated with positive epistasis. While epistasis is thought to occur commonly during the evolution of viruses, the extent of epistasis in influenza, and its role in the evolution of immune escape and drug resistant mutants, remains to be systematically investigated. Here putative epistatic mutations within H3 hemagglutinin in type A influenza are identified where leading parent mutations were found to predominate within reported antigenic sites of the protein.

Mutational analysis employing a phylogenetic mass tree approach in a study of the evolution of the influenza virus.

A mass based approach has been advanced to enable mutations associated with the evolution of proteins to be both charted and interrogated using phylogenetic trees built solely from the masses of peptides generated upon protein proteolysis. The modified MassTree algorithm identifies and displays all such mutations and calculates the frequency of a particular mutation across a tree. Its significance in terms of its position(s) on the tree is scored, where mutations that occur toward the basis of the tree are weighted more favourably.