Identifying New Clusterons: Application of TBEV Analyzer 3.0

Abstract

Early knowledge about novel emerging viruses and rapid determination of their characteristics are crucial for public health. In this context, development of theoretical approaches to model viral evolution are important. The clusteron approach is a recent bioinformatics tool which analyzes genetic patterns of a specific E protein fragment and provides a hierarchical network structure of the viral population at three levels: subtype, lineage, and clusteron. A clusteron is a group of strains with identical amino acid (E protein fragment) signatures; members are phylogenetically closely related and feature a particular territorial distribution. This paper announces TBEV Analyzer 3.0, an analytical platform for rapidly characterizing tick-borne encephalitis virus (TBEV) strains based on the clusteron approach, workflow optimizations, and simplified parameter settings. Compared with earlier versions of TBEV Analyzer, we provide theoretical and practical enhancements to the platform. Regarding the theoretical aspect, the model of the clusteron structure, which is the core of platform analysis, has been updated by analyzing all suitable TBEV strains available in GenBank, while the practical enhancements aim at improving the platform's functionality. Here, in addition to expanding the strain sets of prior clusterons, we introduce eleven novel clusterons through our experimental results, predominantly of the European subtype. The obtained results suggest effective application of the proposed platform as an analytical and exploratory tool in TBEV surveillance.

Keywords: TBEV analyzer; clusteron approach; epidemiology; evolution; monitoring.

Figure 1

The overall schema of the computational pipeline for clusteron structure application. The pipeline generally includes alignment, identifying a target coding sequence of an E protein fragment, constructing the phylogenetic tree, and inferring/verifying the assigned clusteron to the query. Note that assigning a clusteron to a query requires verification at both the nucleotide and amino acid levels.

Figure 2

Updated version of the clusteron structure. The platform recently identified eleven new clusterons, which are highlighted in orange. Homoplastic clusterons are connected together by dotted lines.

Figure 3

Visualization of the clusteron-specific amino acid signature on the surface of the E protein (PDB ID: 1SVB [25]). The visualization is generated by the PDBe Molstar application. The highlighted amino acids show the Baikalian subtype signature (CS ID: 4A).

Figure 4

Visualization of viral distribution on the geographical map. The visualization is generated by the web application “Kepler.gl” [29]. The figure shows a heatmap of strains for clusteron 3A across the Ural region.