Biology subjects

Roberts-Sengier, W.

Publications and source records attributed to Roberts-Sengier, W..

3 recordsLinked to original sources

bioRxiv2025

BaGPipe: an automated, reproducible, and flexible pipeline for bacterial genome-wide association studies

Microbial genome-wide association study (GWAS) tools often require manual data processing steps, lack comprehensive workflows, and are limited by scalability issues, thus hindering the exploration of bacterial genetic traits. To address these challenges, we developed BaGPipe, an automated and flexible bacterial GWAS pipeline built using Nextflow and incorporating Pyseer for association analysis. BaGPipe integrates all essential components of a bacterial GWAS--spanning pre-processing, statistical analysis, and downstream visualisation--into a unified workflow that is reproducible and easy to deploy across diverse computational environments. BaGPipe was validated on a publicly available dataset of Streptococcus pneumoniae whole-genome sequences, and reproduced published findings with improved computational efficiency. BaGPipe was then applied to a dataset of Staphylococcus aureus whole-genome sequences, successfully identifying known and novel antibiotic resistance associations. By offering an accessible, efficient, and reproducible platform, BaGPipe accelerates bacterial GWAS and facilitates deeper exploration into the genetic underpinnings of phenotypic traits. Impact StatementThe increasing availability of bacterial genome sequences has created an opportunity for robust, reproducible tools to facilitate the discovery of novel genotype-phenotype associations. Despite the demonstrated utility of genome-wide association studies (GWAS) in identifying genetic determinants of disease, toxicity and antibiotic resistance, existing tools for bacterial GWAS often involve fragmented workflows requiring extensive manual intervention, limiting their adoption and reproducibility. Here, we introduce BaGPipe, a fully integrated bacterial GWAS pipeline that automates pre-processing, statistical analysis, and visualisation, thereby streamlining the entire workflow. With its flexibility, scalability, and ease of use, BaGPipe makes bacterial GWAS more accessible to researchers, enabling faster and more reliable insights into microbial genetics. This is an important step towards overcoming the computational and logistical barriers that have constrained bacterial GWAS, ultimately accelerating research into microbial evolution, resistance mechanisms, and the genetic basis of other key phenotypic traits. Data SummaryBaGPipe is freely available at https://github.com/sanger-pathogens/BaGPipe. The Streptococcus pneumoniae input dataset is available from the Pyseer tutorial (https://pyseer.readthedocs.io/en/master/tutorial.html#). The Staphylococcus aureus sequencing assemblies can be sourced from their ERS accession numbers provided in supplementary data. The reference assemblies, listed in the supplementary, can be sourced from NCBI.

bioinformatics↗

bioRxiv2024

High-quality transcriptome profile of Treponema pallidum subsp. pallidum: confirmation of transcriptional landscape

Syphilis remains a critical global health challenge due to its potential for severe complications and the increase in its incidence rate over recent years. Until recently, the infectious agent of syphilis, Treponema pallidum subsp. pallidum (TPA), could not be cultured in vitro. Advances in co-culture techniques have finally allowed for effective long-term cultivation of TPA, providing a platform to study its biology. Limited transcriptional data from TPA have been reported so far and many genes in treponemal genomes are annotated based on in silico prediction of putative coding sequences without functional validation. To inform future syphilis vaccine development, experimental validation of in silico predicted genes coupled with functional annotation is necessary. In this study, strand-specific RNA-sequencing was used to reconstruct a high-quality transcriptome profile of TPA, confirming the active transcription of genes previously annotated as hypothetical, paving the way for more accurate identification of vaccine target candidates. Our transcriptomic data also revealed, for the first time, the organization of genes into transcription units, an abundance of anti-sense RNAs, and transcripts from intergenic regions, providing crucial insights for future functional genomics studies of TPA. Author SummaryIn our study, we explored the genetic activity of the bacteria responsible for syphilis, Treponema pallidum subsp. pallidum (TPA). Although syphilis has been a known disease for centuries, the bacterium causing it has remained difficult to study because it couldnt be easily grown in the lab. Recently, new techniques have allowed us to cultivate TPA successfully, enabling deeper investigation into its genetics. By employing directional RNA sequencing, we have mapped out which genes are actively transcribed, including those previously labeled as hypothetical. Our study has also revealed new insights into the gene organization and uncovered the presence of antisense RNA, which may regulate gene expression. These findings offer critical information that could inform future research and vaccine development efforts for syphilis.

microbiology↗

bioRxiv2022

Nanopore sequencing for real-time genomic surveillance of Plasmodium falciparum

Malaria is a global public health priority causing over 600,000 deaths annually, mostly young children living in Sub-Saharan Africa. Molecular surveillance can provide key information for malaria control, such as the prevalence and distribution of antimalarial drug resistance. However, genome sequencing capacity in endemic countries can be limited. Here, we have implemented an end-to-end workflow for P. falciparum genomic surveillance in Ghana using Oxford Nanopore Technologies, targeting antimalarial resistance markers and the leading vaccine antigen circumsporozoite protein (csp). The workflow was rapid, robust, accurate, affordable and straightforward to implement, and could be deployed using readily collected dried blood spot samples. We found that P. falciparum parasites in Ghana had become largely susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine (SP) resistance, and no evidence of artemisinin resistance. Multiple Single Nucleotide Polymorphism (SNP) differences from the vaccine csp sequence were identified, though their significance is uncertain. This study demonstrates the potential utility and feasibility of malaria genomic surveillance in endemic settings using Nanopore sequencing.

genomics↗