Biology subjects

Wickham, G. J.

Publications and source records attributed to Wickham, G. J..

3 recordsLinked to original sources

bioRxiv2026

EISCA and EISTA: Full-Spectrum Pipelines for Single-Cell and Spatial Transcriptomics Analysis

Single-cell and spatial transcriptomics are transforming our understanding of cellular heterogeneity and tissue organization, yet their analytical complexity remains a major bottleneck. Here, we present EISCA and EISTA, two standardized, end-to-end pipelines for single-cell RNA-seq and imaging-based spatial transcriptomics analysis. Built on the Nextflow nf-core framework, both pipelines implement modular, scalable, and reproducible workflows spanning primary, secondary, and tertiary analyses, from raw data processing to advanced downstream analyses. EISCA supports droplet- and plate-based scRNA-seq technologies, while EISTA is tailored for high-resolution spatial platforms including Vizgen MERFISH and 10x Xenium. Together, they integrate state-of-the-art methods for quality control, normalization, clustering, integration, cell-type annotation, differential expression, and cell-cell communication, with EISTA further enabling spatial statistical analyses. A central design principle is to balance standardization with flexibility: workflows can be executed end-to-end or modularly, enabling iterative, exploratory analyses with minimal overhead. Both pipelines deliver rapid preliminary results alongside an out-of-the-box report, facilitating immediate data assessment and accelerating downstream discovery. Case studies in plant immunity and human sepsis demonstrate that EISTA and EISCA reproducibly can be used to recover biologically meaningful insights. Collectively, these pipelines provide efficient, flexible, and scalable solutions for comprehensive single-cell and spatial transcriptomics analyses.

bioinformatics↗

bioRxiv2025

Tissue destruction during food spoilage is associated with the formation of biofilms by Pseudomonas species

Members of the Pseudomonas genus are common spoilers of a range of meat, dairy and vegetable products. While we have a good understanding of the Pseudomonas species typically responsible for spoilage, we know very little about how these bacteria interact with food surfaces during spoilage. Here we assessed the spoilage capabilities of a large panel (n=124) of Pseudomonas species food-derived isolates on meat (chicken) and leafy greens (spinach). Most isolates (71/124) were capable of spoiling both foods, but some were only capable of spoiling only chicken (21/124) or spinach (23/124), or neither (9/124). Our data also demonstrated that the type of fresh food the strain was isolated from influenced spoilage capabilities: strains isolated from meat were likely to spoil both chicken and spinach, while those isolated from leafy greens were more likely to spoil only spinach. We used fluorescence microscopy to visualise how Pseudomonas spoilage species interacted with the meat or leaf tissue and observed significant tissue destruction associated with biofilm formation. For chicken, this was associated with the formation of dense biofilm pillars that penetrated deep into the tissue. For spinach we observed biofilms on the leaf in areas of tissue degradation. Finally, we explored the correlation between potentially relevant phenotypes (in vitro biofilm, motility and secreted enzyme production) and spoilage capabilities. There was no significant correlation between any of these phenotypes and spoilage, except for secreted protease activity and chicken spoilage. Overall, this study increases our understanding of processes involved in food spoilage by Pseudomonas species.

microbiology↗

bioRxiv2019

Antibiotics select for novel pathways of resistance in biofilms

Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response to sub-inhibitory concentrations of drugs. Here we used a biofilm evolution model to show that biofilms of a model food borne pathogen, Salmonella Typhimurium rapidly evolve in response to exposure to three clinically important antibiotics. Whilst the model strongly selected for improved biofilm formation in the absence of any drug, once antibiotics were introduced the need to adapt to the drug was more important than the selection for improved biofilm formation. Adaptation to antibiotic stress imposed a marked cost in biofilm formation, particularly evident for populations exposed to cefotaxime and azithromycin. We identified distinct resistance phenotypes in biofilms compared to corresponding planktonic control cultures and characterised new mechanisms of resistance to cefotaxime and azithromycin. Novel substitutions within the multidrug efflux transporter, AcrB were identified and validated as impacting drug export as well as changes in regulators of this efflux system. There were clear fitness costs identified and associated with different evolutionary trajectories. Our results demonstrate that biofilms adapt rapidly to low concentrations of antibiotics and the mechanisms of adaptation are novel. This work will be a starting point for studies to further examine biofilm specific pathways of adaptation which inform future antibiotic use.

microbiology↗