Biology subjects

O'Neill, R.

Publications and source records attributed to O'Neill, R..

7 recordsLinked to original sources

bioRxiv2025

An Evaluation of the Efficacy of Single-Echo and Multi-Echo fMRI Denoising Strategies

Resting-state functional magnetic resonance imaging (rsfMRI) is commonly used to study brain-wide patterns of inter-regional functional coupling (FC). However, the resulting signals are vulnerable to multiple sources of noise, such as those related to non-neuronal physiological fluctuations and head motion, which can alter FC estimates and influence their associations with behavioral outcomes. The best strategy for acquiring and processing rsfMRI data to mitigate noise remains an open question. In this study of 358 healthy individuals, we compared the denoising efficacy of 60 multi-echo (ME) and 30 single-echo (SE) rsfMRI preprocessing pipelines across six distinct measures of data quality. We also evaluated how each pipeline influences the effect sizes of FC-based predictive models of personality and cognitive measures estimated via cross-validated kernel ridge regression. We found that ME pipelines generally showed superior denoising efficacy to SE pipelines, but that no single pipeline was associated with both superior denoising efficacy and behavioural prediction. Using a heuristic scheme to rank pipelines across benchmark evaluations, we found that an ME acquisition combined with Automatic Removal of Motion Artifacts Independent Component Analysis (ICA-AROMA) and Regressor Interpolation at Progressive Time Delays (RIPTiDe) offered a reasonable compromise between denoising efficacy and brain-behavior predictions for both ME and SE data. In general, ME pipelines ranked more highly than SE pipelines. These findings support the use of ME acquisitions in future work but suggest that no single denoising pipeline should be considered optimal for all purposes.

neuroscience↗

bioRxiv2025

Mink by mink: stitching together signatures of subspecies adaptation through a pangenome of threatened mustelids

The American mink (Neogale vison), a semi-aquatic Mustelidae carnivoran with broad ecological range across North America, includes several putative subspecies of conservation concern. To investigate the evolutionary history and adaptive signatures of mink subspecies, chromosome-scale genome assemblies were generated for six individuals representing three southern subspecies: N. vison evergladensis, N. vison vulgivaga, and N. vison lutensis. Genomes were assembled using Illumina short reads, scaffolded with Oxford Nanopore long reads, and aligned to the phased N. vison reference genome. Assemblies ranged from 75.9% to 97.8% completeness, with five meeting thresholds for pangenome construction. A reference-free pangenome revealed an open architecture, highlighting considerable subspecies diversity. Subspecies-specific gene enrichment reflected adaptation: N. vison evergladensis showed enrichment in traits related to reproduction and sensory function; N. vison vulgivaga in cytoskeletal remodeling and oxidative stress; and N. vison lutensis in neuronal development, synaptic plasticity and cellular stress pathways. Assessment of the mitogenomes resolved N. vison lutensis as a distinct lineage, while nuclear data supported broader subspecies divergence but lacked fine scale resolution. N. vison evergladensis showed multiple signatures of small population size, including inbreeding coefficients (FROH) above 0.5, and displayed consistent population decline over time via demographic inference. Our findings support evergladensis as a distinct subspecies, supported by both the mitogenome phylogeny, and significant functional differentiation. As the first pangenome for Mustelidae, this study demonstrates the power of integrating cross-platform sequencing with natural history specimens to improve the resolution on signatures of adaptation and inform conservation policy and management of threatened populations.

genomics↗

bioRxiv2025

TNF signaling maintains local restriction of bacterial founder populations in intestinal and systemic sites during oral Yersinia infection

Enteroinvasive bacterial pathogens are responsible for an enormous worldwide disease burden that critically affects the young and immunocompromised. Yersinia pseudotuberculosis is a Gram-negative enteric pathogen, closely related to the plague agent Y. pestis, that colonizes intestinal tissues, induces the formation of pyogranulomas along the intestinal tract, and disseminates to systemic organs following oral infection of experimental rodents. Prior studies proposed that systemic tissues were colonized by a pool of intestinal replicating bacteria distinct from populations within Peyers patches and mesenteric lymph nodes. Whether bacteria within intestinal pyogranulomas serve as the source for systemic dissemination, and the relationship between bacterial populations within different tissue sites is poorly defined. Moreover, the factors that regulate Yersinia colonization and dissemination are not well understood. Here, we demonstrate, using Sequence Tag-based Analysis of Microbial Populations in R (STAMPR), that remarkably small founder populations independently colonize intestinal and systemic tissues. Notably, intestinal pyogranulomas contain clonal populations of bacteria that are restricted and do not spread to other tissues. However, populations of Yersinia are shared among systemic organs and the blood, suggesting that systemic dissemination occurs via hematogenous spread. Finally, we demonstrate that TNF signaling is a key contributor to the bottlenecks limiting both tissue colonization and lymphatic dissemination of intestinal bacterial populations. Altogether, this study reveals previously undescribed aspects of infection dynamics of enteric bacterial pathogens. ImportanceBacterial escape from the intestine can lead to severe disease, including sepsis, organ damage, and death. However, the intestinal bacterial population dynamics governing the colonization of mucosal and systemic tissues and the intestinal sites that seed systemic spread are not clear. Yersinia pseudotuberculosis is a rodent and human intestinal pathogen closely related to the plague agent and provides a natural rodent-adapted model to study systemic bacterial dissemination. Our findings define the infection dynamics of enteric Yersinia and the impact of the innate immune system on Yersinia colonization of the intestine and systemic organs.

microbiology↗

bioRxiv2023

Conserving a threatened North American walnut: a chromosome-scale reference genome for butternut (Juglans cinerea)

With the advent of affordable and more accurate third generation sequencing technologies and the associated bioinformatic tools, it is now possible to sequence, assemble, and annotate more species of conservation concern than ever before. Juglans cinerea, commonly known as butternut or white walnut, is a member of the walnut family, native to the Eastern United States and Southeastern Canada. The species is currently listed as Endangered on the IUCN Red List due to decline from an invasive fungus known as Ophiognomonia clavigignenti-juglandacearum (Oc-j) that causes butternut canker. Oc-j creates visible sores on the trunks of the tree which essentially starves and slowly kills the tree. Natural resistance to this pathogen is rare. Conserving butternut is of utmost priority due to its critical ecosystem role and cultural significance. As part of an integrated undergraduate and graduate student training program in biodiversity and conservation genomics, the first reference genome for Juglans cinerea is described here. This chromosome-scale 539 Mb assembly was generated from over 100X coverage of Oxford Nanopore long reads and scaffolded with the Juglans mandshurica genome. Scaffolding with a closely related species oriented and ordered the sequences in a manner more representative of the structure of the genome without altering the sequence. Comparisons with sequenced Juglandaceae revealed high levels of synteny and further supported J. cinereas recent phylogenetic placement. Comparative assessment of gene family evolution revealed a significant number of contracting families, including several associated with biotic stress response.

genomics↗

bioRxiv2023

A TNF-IL-1 circuit controls Yersinia within intestinal granulomas

SummaryMonocytes restrict Yersinia infection within intestinal granulomas. Here, we report that monocyte-intrinsic TNF signaling drives production of IL-1 that signals to non-hematopoietic cells to control intestinal Yersinia infection within granulomas. Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. Yersinia pseudotuberculosis colonizes the intestinal mucosa and induces recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas that control the bacterial infection. Inflammatory monocytes are essential for control and clearance of Yersinia within intestinal pyogranulomas, but how monocytes mediate Yersinia restriction is poorly understood. Here, we demonstrate that TNF signaling in monocytes is required for bacterial containment following enteric Yersinia infection. We further show that monocyte-intrinsic TNFR1 signaling drives production of monocyte-derived interleukin-1 (IL-1), which signals through IL-1 receptor on non-hematopoietic cells to enable pyogranuloma-mediated control of Yersinia infection. Altogether, our work reveals a monocyte-intrinsic TNF-IL-1 collaborative circuit as a crucial driver of intestinal granuloma function, and defines the cellular target of TNF signaling that restricts intestinal Yersinia infection.

immunology↗

bioRxiv2022

A comprehensive library of canonical and non-canonical MHC class I antigens for cancer vaccine development.

A longstanding disconnect between the growing number of MHC Class I immunopeptidomic studies and genomic medicine hinders cancer vaccine design. We develop COD-dipp to genomically map the full spectrum of detected canonical and non-canonical (non-exonic) MHC Class I antigens from 26 cancer studies. We demonstrate that patient mutations in regions overlapping physically identified antigens better predict immunotherapy response when compared to neoantigen predictions. We suggest a vaccine design approach using 140,966 highly immune-visible regions of the genome annotated by their expression and haplotype frequency in the human population. These regions tend to be highly conserved, mutated in cancer and harbor 7.8 times more immunogenicity. Intersecting pan-cancer mutations with these immune surveilled regions revealed a potential to create off-the-shelf multi-epitope vaccines against public neoantigens. Here we release COD-dipp, a cancer vaccine toolkit as a web-application (https://www.proteogenomics.ca/COD-dipp) and open-source high-throughput resource.

bioinformatics↗

bioRxiv2018

Tissue-specific transcriptome for Poeciliopsis prolifica reveals evidence for genetic adaptation related to the evolution of a placental fish.

The evolution of the placenta is an excellent model to examine the evolutionary processes underlying adaptive complexity due to the recent, independent derivation of placentation in divergent animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with respect to variation in degree of post-fertilization maternal provisioning among closely related sister species. In this study, we present a detailed examination of a new reference transcriptome sequence for the live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, \"non-coding\" sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifically, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event.

genomics↗