Biology subjects

Skvortsov, T.

Publications and source records attributed to Skvortsov, T..

6 recordsLinked to original sources

bioRxiv2026

Ptolemaea: consensus, comprehensive annotation of antiviral defence systems in bacterial genomes

MotivationBacteria carry a large repertoire of antiviral defence systems, our knowledge of which is expanding rapidly. Several bioinformatics tools now exist to identify them. Though powerful, these tools can differ in the models they use and the nomenclature they return, thus a single tool could both miss an annotation and disagree with its peers. ResultsHere we describe Ptolemaea, a pipeline for harmonising phage-defence annotations across multiple tools by reconciling PADLOC, DefenseFinder, and a bidirectional BLAST. Over a common predicted set of proteins, Ptolemaea provides a consensus annotation list per genome. The pipeline is not intended to outperform or replace its component tools; its purpose is to maximise the number of defence systems recovered from a genome and to make disagreements between tools explicit and resolvable. We demonstrate the pipeline on 700 complete genomes spanning the ESKAPE pathogens and Escherichia coli, recovering 32,509 defence annotations, of which 50.6% were supported by more than one annotation source. AvailabilityThe Ptolemaea pipeline is freely available at https://github.com/ecampbell50/Ptolemaea. Supplementary informationGenome accessions used in this analysis can be found in S1, and script for genome retrieval in S2. Collated consensus annotation counts can be found in S3, while all raw tool outputs and curated decisions for each species can be found in S4-10.

bioinformatics↗

bioRxiv2025

A novel approach to Caudoviricetes taxonomy utilising whole proteome structure-structure comparison

Viral proteins often evolve so rapidly that sequence similarity is lost even among conserved functional genes, complicating phylogenetic analysis and classification. This challenge is acute for Caudoviricetes, a highly diverse class of dsDNA tailed bacteriophages recently redefined by the International Committee on Taxonomy of Viruses (ICTV). To address the limitations of sequence-based taxonomy, we present a structure-based classification framework using whole-proteome structural clustering. From 4,082 exemplar genomes, we predicted 445,098 protein structures with ESMFold and clustered them using Foldseek. Genomes were encoded as binary profiles of structural fold presence, and phylogenetic distances were inferred and normalized using Relative Evolutionary Divergence (RED). This yielded a revised structural taxonomy comprising 159 orders, 267 families, 502 subfamilies, and 1,189 genera. We also introduce PhagePleats, a Python tool for classifying novel phage genomes based on structural similarity. Our approach highlights the utility of protein structure for resolving distant viral relationships.

microbiology↗

bioRxiv2024

Decoding Protein Dynamics: ProFlex as a Linguistic Bridge in Normal Mode Analysis

Artificial intelligence has revolutionized structural bioinformatics, with AlphaFold being arguably the most impactful development to date. The structural atlases generated by these methods present significant opportunities for unraveling biological mysteries, but also pose challenges in leveraging such massive datasets effectively. In this work, we explore the dynamic landscape of hundreds of thousands of AlphaFold-predicted structures using normal mode analysis. The resulting data is used to define an alphabet summarizing relative protein flexibility, termed ProFlex. We believe that refining and further applying ProFlex-like approaches offers novel opportunities for understanding protein function and enhancing other methods.

bioinformatics↗

bioRxiv2023

Application of a Machine Learning Approach Towards the Targeted Identification of Phage Depolymerases

Biofilm production plays a clinically significant role in the pathogenicity of many bacteria, limiting our ability to apply antimicrobial agents and contributing in particular to the pathogenesis of chronic infections. Bacteriophage depolymerases, leveraged by these viruses to circumvent biofilm mediated resistance, represent a potentially powerful weapon in the fight against antibiotic resistant bacteria. Such enzymes are able to degrade the extracellular matrix that is integral to the formation of all biofilms and as such would allow complementary therapies or disinfection procedures to be successfully applied. In this manuscript, we describe the development and application of a machine learning based approach towards the identification of phage depolymerases. We demonstrate that on the basis of a relatively limited number of experimentally proven enzymes and using an amino acid derived feature vector that the development of a powerful model with an accuracy on the order of 90% is possible, showing the value of such approaches in the discovery of novel therapeutic agents.

bioinformatics↗

bioRxiv2020

Rapid Mycobacterium tuberculosis spoligotyping from uncorrected long reads using Galru

Spoligotyping of Mycobacterium tuberculosis provides a subspecies classification of this major human pathogen. Spoligotypes can be predicted from short read genome sequencing data; however, no methods exist for long read sequence data such as from Nanopore or PacBio. We present a novel software package Galru, which can rapidly detect the spoligotype of a Mycobacterium tuberculosis sample from as little as a single uncorrected long read. It allows for near real-time spoligotyping from long read data as it is being sequenced, giving rapid sample typing. We compare it to the existing state of the art software and find it performs identically to the results obtained from short read sequencing data. Galru is freely available from https://github.com/quadram-institute-bioscience/galru under the GPLv3 open source licence.

bioinformatics↗

bioRxiv2019

dsDNA Phage Andromeda with Quasispecies-like Genomic Hypervariability Establishes a Novel Phylogenetic Branch Within the Autographivirinae Subfamily

A new lytic bacteriophage Andromeda, specific to the economically important plant pathogen Pseudomonas syringae, was isolated and characterised. It belongs to the Podoviridae family, Autographivirinae subfamily and possesses a linear dsDNA genome of 40,008 bp with four localised nicks. Crucially, Andromedas genome has no less than 80 hypervariable sites (SNPs), which show genome wide distribution resulting in heterogenous populations of this phage reminiscent of those of RNA virus quasispecies. Andromeda has no nucleotide sequence homology to phage phiNFS, a member of phiKMVviruses, in which a similar phenomenon was discovered. We show that Andromeda and Andromeda-related phages form a group within the Autographivirinae, designated here as the "ExophiKMVviruses". The "ExophiKMVviruses" were revealed to share conservation of gene order with core phiKMVviruses despite their sequence-based relationship to SP6-related phages. Our findings suggest that genomic hypervariability might be a feature that occurs among various Autographivirinae groups.

microbiology↗