Biology subjects

Bass, A.

Publications and source records attributed to Bass, A..

8 recordsLinked to original sources

bioRxiv2026

TrIdent - An R package to automate transductomics analysis of virus-like particle mediated DNA mobilization

BackgroundTransduction is a form of horizontal gene transfer in which bacterial DNA is packaged and transferred by virus-like particles (VLPs). Transductomics is a sequencing-based method used to detect DNA carried by VLPs. During transductomics analysis, reads from a samples ultra-purified VLPs are mapped to metagenomic contigs assembled from the same samples whole-community. The read mapping produces coverage patterns that require a time-consuming manual inspection and classification process which makes the methods use unfeasible for datasets with many samples. ResultsWe developed a novel algorithm, TrIdent (Transduction Identification), that uses pattern-matching to automate the transductomics data analysis and that is available as an R package (https://jlmaier12.github.io/TrIdent/). There is no software equivalent to TrIdent so we compared TrIdents classifications of transductomics datasets to classifications made by human classifiers. TrIdents classifications were generally comparable to the manual classifications on a previously generated, manually classified transductomics dataset. When applied to newly generated transductomics data from the murine microbiota, TrIdent agreed with two independent human classifiers as much as the two independent human classifications agreed with each other. TrIdent classified transductomics datasets in a fraction of the time needed by human classifiers, and the classifications produced by TrIdent are fully reproducible. We used TrIdent to explore three murine gut transductomes and found that bacterial DNA associated with the Oscillospiraceae and Turicibacteraceae families was highly enriched in the DNA packaged by VLPs as compared to the whole community metagenomes. ConclusionsThe TrIdent software is a more accessible, more efficient, and more reproducible alternative to the manual inspection of read coverage patterns previously required for transductomics data analysis. To demonstrate the application of TrIdent, we analyzed transductomics datasets from murine fecal pellets and showed that specific low abundance bacterial families appear to be heavily involved in transduction.

genomics↗

bioRxiv2025

Sexual dimorphism in zymosan-induced arthritis is linked with a higher IFN response in myeloid cell subsets that faithfully recapitulate RA synovial cell clusters

A key feature of rheumatoid arthritis (RA) is sexual dimorphism, with a higher incidence of RA in females. Myeloid cells are key drivers of the inflammatory effector phase of RA, but little is known about their contribution to a sexually dimorphic arthritis phenotype. We wished to utilize an arthritis model that recapitulates RA pathogenic myeloid cell subsets defined by single cell transcriptome analysis to investigate sex differences in human disease-relevant cell types and related molecular pathways. We developed a computational strategy that rigorously maps scRNAseq-defined mouse arthritis myeloid cells and clusters onto previously defined RA subsets. Synovial myeloid cells in the zymosan-induced arthritis (ZIA) model closely recapitulated four pathogenic RA myeloid cell subsets, strongly supporting the disease-relevance of the ZIA model. ZIA also effectively modeled myeloid cells in immune checkpoint inhibitor arthritis (ICI-A). These RA, ICI-A and ZIA myeloid cells express genes in TNF-NF-kB, PGE2, and IFN-STAT pathways. In ZIA, an induction phase dominated by cell clusters expressing NF-kB and PGE2 pathways transitioned to peak arthritis characterized by cell subsets co-expressing NF-kB and IFN pathways, as occurs in RA and various inflammatory diseases. Female mice exhibited increased arthritis linked with early induction of interferon-stimulated genes and increased expansion of IFN signature-expressing cell subsets. Our study identifies a computational strategy and animal model that enables investigation of recently described pathogenic myeloid cell subsets, and links increased arthritis in female mice with specific myeloid cell subsets that exhibit a stronger IFN response.

immunology↗

bioRxiv2024

Opposing Regulation of TNF Responses and IL-1b+ Macrophages by PGE2-cAMP and IFN-g Signaling

IL-1{beta}-expressing macrophages have been described in rheumatoid arthritis (RA), immune checkpoint inhibitor-induced inflammatory arthritis (ICI-arthritis), and pancreatic cancer and proposed to be pathogenic. In RA and pancreatic cancer IL-1{beta}+ macrophages express genes cooperatively induced by PGE2 and TNF signaling, but mechanisms that induce these cells and the extent to which they contribute to arthritic phenotypes are not known. In this study we used an integrated transcriptomic and epigenomic analysis in primary human monocytes to study PGE2-TNF crosstalk, and how it is regulated by IFN-{gamma}, as occurs in RA synovial macrophages. We identified a TNF + PGE2 (TP) induced gene expression signature that is enriched in a previously identified IL1{beta}+ RA monocytic subset defined by scRNAseq and includes genes in pathogenic IL-1, Notch and neutrophil chemokine pathways. A similar TP gene expression signature was apparent in an IL-1{beta}+ macrophage subset newly identified by scRNAseq in ICI-arthritis. Reference mapping revealed that ICI-arthritis myeloid cells map primarily onto four previously defined RA synovial monocytic clusters, and the TP signature extends beyond IL-1{beta}+ cells to subsets of adjacent clusters, suggestive of a new functional monocyte subset. TP signature genes are distinct from canonical inflammatory NF-{kappa}B target genes such as TNF, IL6 and IL12B and are activated by cooperation of PGE2-induced AP-1, CEBP and NR4A family transcription factors with TNF-induced NF-{kappa}B activity. Unexpectedly, IFN-{gamma} suppressed induction of AP-1, CEBP and NR4A activity to ablate induction of IL-1, Notch and neutrophil chemokine genes, while promoting expression of distinct inflammatory genes such as TNF and T cell chemokines like CXCL10. The opposing cross-regulation of PGE2 and IFN signaling in vitro was reflected in vivo in mutually exclusive expression of TP and IFN signatures in different cell clusters in RA and ICI-arthritis monocytes. These results reveal the basis for synergistic induction of inflammatory genes by PGE2 and TNF, and a novel regulatory axis whereby IFN-{gamma} and PGE2 oppose each other to determine the balance between two distinct TNF-induced inflammatory gene expression programs relevant for RA and ICI-arthritis.

immunology↗

bioRxiv2021

Atlantic salmon farms are a likely source of Tenacibaculum maritimum infection in migratory Fraser River sockeye salmon

Infectious disease from domestic hosts, held for agriculture, can impact wild species that migrate in close proximity, potentially reversing selective advantages afforded by migration. For sockeye salmon in British Columbia, Canada, juveniles migrate past numerous Atlantic salmon farms from which they may acquire a number of infectious agents. We analyse patterns of molecular detection in juvenile sockeye salmon for one bacterial pathogen, Tenacibaculum maritimum, known to cause disease in fish species around the globe and to cause mouthrot disease in farmed Atlantic salmon in BC. Our data show a clear peak in T. maritimum detections in the Discovery Islands region of BC, where sockeye migrate close to salmon farms. Using well established differential-equation models to describe sockeye migration and T. maritimum infection spread, we fit models to our detection data to assess support for multiple hypotheses describing farm- and background-origin infection. Despite a data-constrained inability to resolve certain epidemiological features of the system, such as the relative roles of post infection mortality and recovery, our models clearly support the role of Discovery-Islands salmon farms in producing the observed patterns. Our best models (with 99.8% empirical model support) describe relatively constant (background) infection pressure, except around Discovery-Islands salmon farms, where farm-origin infection pressure peaked at 12.7 (approximate 95% CI: 4.5 to 31) times background levels. Given the evidence for farm-origin transfer of T. maritimum to Fraser-River sockeye salmon, the severity of associated disease in related species, and the imperilled nature of Fraser River sockeye generally, our results suggest the need for a more precautionary approach to managing farm/wild interactions in sockeye salmon.

ecology↗

bioRxiv2021

Origins of cancer genome complexity revealed by haplotype-resolved genomic analysis of evolution of Barretts esophagus to esophageal adenocarcinoma

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we performed haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barretts esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identified distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.

genomics↗

bioRxiv2020

To hum or not to hum: Neural transcriptome signature of courtship vocalization in a teleost fish

For many animal species, vocal communication is a critical social behavior, often a necessary component of reproductive success. In addition to the role of vocal behavior in social interactions, vocalizations are often demanding motor acts. Through understanding the genes involved in regulating and permitting vertebrate vocalization, we can better understand the mechanisms regulating vocal and, more broadly, motor behaviors. Here, we use RNA-sequencing to investigate neural gene expression underlying the performance of an extreme vocal behavior, the courtship hum of the plainfin midshipman fish (Porichthys notatus). Single hums can last up to two hours and may be repeated throughout an evening of courtship activity. We asked whether vocal behavioral states are associated with specific gene expression signatures in key brain regions that regulate vocalization by comparing transcript levels in humming versus non-humming males. We find that the circadian-related genes period3 and Clock are significantly upregulated in the vocal motor nucleus and preoptic area-anterior hypothalamus, respectively, in humming compared to non-humming males, indicating that internal circadian clocks may differ between these divergent behavioral states. In addition, we identify suites of differentially expressed genes related to synaptic transmission, ion channels and transport, hormone signaling, and metabolism and antioxidant activity that may permit or support humming behavior. These results underscore the importance of the known circadian control of midshipman humming and provide testable candidate genes for future studies of the neuroendocrine and motor control of energetically demanding courtship behaviors in midshipman fish and other vertebrate groups.

neuroscience↗

bioRxiv2020

Evolution and Ecology in Widespread Acoustic Signaling Behavior Across Fishes

Acoustic signaling by fishes has been recognized for millennia, but is typically regarded as comparatively rare within ray-finned fishes; as such, it has yet to be integrated into broader concepts of vertebrate evolution. We map the most comprehensive data set of volitional sound production of ray-finned fishes (Actinopterygii) yet assembled onto a family level phylogeny of the group, a clade representing more than half of extant vertebrate species. Our choice of family-level rather than species-level analysis allows broad investigation of sonifery within actinopterygians and provides a conservative estimate of the distribution and ancestry of a character that is likely far more widespread than currently known. The results show that families with members exhibiting soniferous behavior contain nearly two-thirds of actinopterygian species, with potentially more than 20,000 species using acoustic communication. Sonic fish families also contain more extant species than those without sounds. Evolutionary analysis shows that sound production is an ancient behavior because it is present in a clade that originating circa 340 Ma, much earlier than any evidence for sound production within tetrapods. Ancestral state reconstruction indicates that sound production is not ancestral for actinopterygians; instead, it independently evolved at least 27 times, compared to six within tetrapods. This likely represents an underestimate for actinopterygians that will change as sonifery is recognized in ever more species of actinopterygians. Several important ecological factors are significantly correlated with sonifery - including physical attributes of the environment, predation by members of other vertebrate clades, and reproductive tactics - further demonstrating the broader importance of sound production in the life history evolution of fishes. These findings offer a new perspective on the role of sound production and acousticcommunication during the evolution of Actinopterygii, a clade containing more than 34,000 species of extant vertebrates.

evolutionary biology↗

bioRxiv2019

Preoptic galanin neuron activation is specific to courtship reproductive tactic in fish with two male morphs

Species exhibiting alternative reproductive tactics (ARTs) provide ideal models for investigating neural mechanisms underlying robust and consistent differences in social behavioral phenotypes between individuals within a single sex. Using phospho-S6 protein (pS6), a neural activity marker, we investigate the activation of galanin-expressing neurons in the preoptic area-anterior hypothalamus (POA-AH) during ARTs in midshipman fish (Porichthys notatus) that have two adult male morphs: type I's that reproduce using an acoustic-dependent courtship tactic or a cuckolding tactic, and type II's that only cuckold. The proportion of pS6-labelled galanin neurons increases during mating by courting type I males, but not cuckolders of either male morph or females, and is not explained by vocalization, eggs in the nest, or cuckolders present during mating. These differences within the same behavioral context indicate a male phenotype-specific role for galanin neurons in mating interactions, providing the most direct evidence to date for the role of a specific neuronal population in the differential activation of one mating behavior over the other in species exhibiting ARTs. More broadly, together with their known role in mammalian mating, the results suggest a deep-rooted, phylogenetically shared function for POA-AH galanin neurons in reproductive behavior. As such, these findings also provide new insights into the evolutionary relationship between POA-AH populations involved in social behavior regulation in teleosts, the most species-rich vertebrate group, with those in the more highly differentiated POA-AH of mammals.

neuroscience↗