Biology subjects

Ryder, D.

Publications and source records attributed to Ryder, D..

5 recordsLinked to original sources

bioRxiv2026

Multiomic and Spatial Profiling of Colorectal Tissue Reveals Viral Persistence and Immune Dysregulation in Long COVID

Long COVID (LC) - a chronic condition characterized by persistent, debilitating symptoms following SARS-CoV-2 infection - has emerged as a major public health challenge. Although many interrelated mechanisms have been proposed as drivers of LC, the root causes have yet to be identified, posing significant challenges for therapeutic development. While many blood-based studies have been conducted, they have not yielded conclusive mechanistic insights into LC pathogenesis. Attention has therefore turned toward direct tissue investigation, with the gastrointestinal (GI) tract becoming a major focus due to evidence that virus or viral components can persist at this site for months to years following an episode of COVID-19. Here, we performed a high-dimensional characterization of colorectal tissue and peripheral blood in a highly characterized cohort of 44 people with LC and 13 recovered controls. We profiled SARS-CoV-2 persistence, host immune responses, and tissue inflammation using bulk and single-cell RNA sequencing, nCounter RNA probe hybridization, quantitative PCR, metagenomic next-generation sequencing, plasma proteomics, high-dimensional spectral flow cytometry, in situ-hybridization/immunohistochemistry, and single-cell digital spatial omics. Our results support a model in which LC is driven by long-term immune dysregulation and perturbations of the regulatory gut immune environment which imply ongoing viral persistence, although direct viral detection was only observed in a subset of participants. Specifically, we identify a tissue-based transcriptional environment in which SARS-CoV-2 activates innate myeloid immune signaling, driving chronic inflammation while simultaneously downregulating pathways responsible for immune-mediated clearance of infected cells, including antigen presentation, phagocytosis, cytotoxic immune cell trafficking, and granzyme production. Importantly, signatures in peripheral blood are considerably weaker than those observed in tissue. Together, these findings provide a direct biological rationale for therapeutic strategies in LC aimed at enhancing or redirecting cytotoxic immune function to overcome immune dysregulation and clear persistent viral reservoirs.

immunology↗

bioRxiv2025

Detection of Macrobrachium rosenbergii golda virus (MrGV) in giant river prawn larvae across Asia through NCBI sequence read archive (SRA) data mining

1Macrobrachium rosenbergii golda virus (MrGV) was first characterised in Macrobrachium rosenbergii larvae in 2020, associated with mass mortalities in multiple Southern Bangladesh prawn hatcheries. MrGV has since been detected in two metatranscriptomic datasets from M. rosenbergii in China and in relation to a larval mortality event in India. The major objective of this study was to further characterise the geographical spread of the virus by mining the NCBI Sequence Read Archive (SRA) database. Utilising a new database, Logan, generated from assembling each SRA dataset, and a custom Snakemake pipeline, we discovered MrGV sequence data in M. rosenbergii SRA datasets from China, Thailand, and India, and determined that presence and relative abundance of MrGV is mostly associated with the larval life stage of M. rosenbergii. These results provide insights into the current prevalence of MrGV globally, suggest the life stages of prawn that should be screened to prevent spread of the virus, and demonstrate how the Logan database can be used to inform epidemiological studies.

bioinformatics↗

bioRxiv2024

Long Amplicon Nanopore Sequencing for Dual-Typing RdRp and VP1 Genes of Norovirus Genogroups I and II in Wastewater

Noroviruses (NoV) are the leading cause of non-bacterial gastroenteritis across the globe with societal costs of US$60.3 billion per annum. Development of a long amplicon nanopore-based method for dual-typing the RNA-dependent RNA polymerase (RdRp) and major structural protein (VP1) regions from a single RNA fragment could improve existing norovirus typing methods. Its application to wastewater-based epidemiology (WBE) and environmental testing could enable the discovery of novel types and improve tracking throughout the population and into aquaculture and recreational water settings. Here, we develop and optimise such a method for wastewater as the sample matrix. Reverse transcription (RT), PCR and library pooling were optimised and a consensus-based bioinformatics pipeline was developed. Inhibitor removal and LunaScript(R) RT gave robust amplification of the {approx}1000 bp RdRP+VP1 amplicon. Platinum Taq polymerase showed good sensitivity and reduced levels non-specific amplification (NSA) when compared to other polymerases. Optimised PCR annealing temperatures significantly reduced NSA (51.3% and 42.4% for GI and GII), increased yield (86.5% for GII) and increased taxa richness (57.7%) for GII. Analysis of three NoV positive faecal samples showed 100% nucleotide similarity with Sanger sequencing. Eight GI genotypes, 11 polymerase types (p-types) and 13 combinations were detected in wastewater along with 4 GII genotypes, 4 p-types and 8 combinations; highlighting the diversity of norovirus taxa present in wastewater in England. The most common genotypes detected in clinical samples were all detected in wastewater while we also commonly detected several GI genotypes not reported in the clinical data. Application of this method into a WBE scheme, therefore, may allow for more accurate measurement of norovirus diversity within the population.

molecular biology↗

bioRxiv2023

Vibrio aestuarianus Clade A and Clade B isolates are associated with Pacific oyster (Crassostrea gigas) disease outbreaks across Ireland

2.Bacteria from the Vibrionaceae family have been implicated in mass mortalities of farmed Pacific oysters (Crassostrea gigas) in multiple countries, leading to substantial impairment for growth in the sector. In Ireland there has been concern that Vibrio have been involved in serious summer outbreaks. There is evidence that Vibrio aestuarianus is increasingly becoming the main pathogen of concern for the Pacific Oyster industry in Ireland. While bacteria belonging to the Vibrio splendidus clade are also detected frequently in mortality episodes, their role in the outbreaks of summer mortality are not well understood. To identify and characterise strains involved in these outbreaks, 43 Vibrio isolates were recovered from Pacific oyster summer mass mortality episodes in Ireland from 2008-2015 and these were whole genome sequenced. Among these, 25 were found to be V. aestuarianus (implicated in disease) and 18 V. splendidus sensu lato (role in disease undetermined). Two distinct clades of V. aestuarianus - Clade A and Clade B - were found that had previously been described as circulating within French oyster culture. The high degree of similarity between the Irish and French V. aestuarianus isolates points to translocation of the pathogen between Europes two major oyster producing countries, probably via trade in spat and other age classes. V. splendidus isolates were more diverse, but the data reveal a single clone of this species that has spread across oyster farms in Ireland. This underscores that Vibrio could be transmitted readily across oyster farms. The presence of V. aestuarianus Clades A and B in not only France but also Ireland adds weight to growing concern that this pathogen is spreading and impacting Pacific oyster production within Europe. 3. OutcomePacific oyster culture in Ireland has increasingly suffered from summer mass mortality events. Many of these mortalities in recent years have been associated with Vibrio aestuarianus; the role of another pathogen, Vibrio splendidus has, so far, remained inconclusive. Here we show that two clades of V. aestuarianus are circulating in Ireland, and that these are members of two clades that have previously caused extensive oyster die offs in France. Their discovery in Ireland is consistent with transport of infected oyster stock between the two countries. Although V. splendidus-like strains in Ireland were highly diverse, a small clonal group was detected that appears to have spread rapidly from a single source to disparate locations in Ireland. Combined, these findings highlight the appearance of a highly pathogenic Vibrio in Ireland, and the risk of transmission between interconnected oyster production industries in Europe. 4. Data summarySequences generated in this study were deposited on the NCBI. Accession number: PRJNA797364. Publicly accessed genomes are listed in Table S2. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2022

De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome

Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae, found at depths between 70 and 2,500 meters on the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. Genomic sequence data for this species is limited. Here, we report a high-quality assembly and annotation of the D. eleginoides genome, generated using a combination of Illumina, PacBio and Omni-C sequencing technologies. To aid the genome annotation, the transcriptome derived from a variety of toothfish tissues was also generated using both short and long read sequencing methods. The final genome assembly was 797.8 Mb with a N50 scaffold length of 3.5 Mb. Approximately 31.7% of the genome consisted of repetitive elements. A total of 35,543 putative protein-coding regions were identified, of which 50% have been functionally annotated. Transcriptomics analysis showed that approximately 64% of the predicted genes (22,617 genes) were found to be expressed in the tissues sampled. Comparative genomics analysis revealed that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared to the same locus in the Antarctic toothfish (Dissostichus mawsoni). This is in agreement with previously published results looking at hybridization signals and confirms that Patagonian toothfish do not possess AFGP coding sequences in their genome. The high-quality genome assembly of the Patagonian toothfish will provide a valuable genetic resource for ecological and evolutionary studies on this and other closely related species.

genomics↗