Biology subjects

Eaton, K.

Publications and source records attributed to Eaton, K..

10 recordsLinked to original sources

bioRxiv2026

Breedbase 2.0 - expanding the functionality for traditional breeding and transgenics

Breedbase ( is a comprehensive, web-based, open-source breeding management and analysis software for plant breeding that was introduced to address gaps with existing software for plant breeding data. Breedbase is continually improved and developed, with new features being added as required by the breeding community. Since its inception, the capabilities of Breedbase were improved to better serve the diverse data modeling needs of additional crops beyond our original ensemble of cassava, banana, yam, sweet potato, tomato, rice, and wheat. We describe here major updates that have been made in the past 4 years, including (1) improved handling of repetitive measurements; (2) a redesigned experimental treatments interface; (3) a more fine-grained user permission system; (4) improved trial quality control workflows; (5) intercropping support; (6) the addition of a decision meeting feature that helps decision makers make the best selection with the available data; (7) transgenics and tracking tools and finally, (8) an improved field layout tool which consolidates several trials in one field. These new features integrate seamlessly with the previous feature set of Breedbase - making it one of the most feature rich breeding management softwares available.

bioinformatics↗

bioRxiv2026

Illuminating the renal response to pH stress with single-nucleus RNA sequencing

Maintenance of whole-body pH is essential for human health. The kidneys play a crucial role in defending pH homeostasis by excreting excess acid in the urine and returning alkali buffers to the blood. Consequently, renal insufficiency causes serious and harmful effects on pH balance. While a serious and common complication of chronic kidney disease (CKD), pH imbalances themselves appear to be catalysts of kidney injury. Renal adaptations to pH imbalances contribute to compensated acid-base disorders and are vital to correcting whole-body pH. However, overstimulation of these adaptive processes can cause renal inflammation and lead to long-term kidney injury. Surprisingly, the acute and chronic effects of pH challenges on the whole kidney are poorly defined. The upregulation of ammoniagenesis in the proximal tubule due to acidosis, and the coordinated secretion of protons from the collecting ducts is a well-documented phenomenon. However, there is a significant gap in knowledge regarding how the other segments of the nephron respond to acidosis or alkalosis. Therefore, to determine the cell-specific impact of overt metabolic acidosis and alkalosis on the kidney, we performed single-nucleus RNA sequencing on male and female WT mice following 48-hours of acid-base challenge (280mM NH4Cl (acid), 280mM NaHCO3 (alkali), 280mM NaCl (isosmotic control)). The results of our studies reveal the sex-specific single-cell transcriptional response by the kidney to pH imbalances, including a proximal straight tubule cell cluster that arises de novo following both acidosis and alkalosis. We label these proximal tubule cells PT S3a and demonstrate that their transcriptional profile is distinct from other injured PT cells that arise from ischemic injury. These studies lay the foundation for future research into the long-term renal adaptations to pH challenges that may lead to renal insufficiency and the development of CKD.

physiology↗

bioRxiv2023

Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility

The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

microbiology↗

bioRxiv2023

Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2

Millions of SARS-CoV-2 genome sequences were collected during the COVID-19 pandemic, forming a dataset of unprecedented richness. Estimated genealogies are fundamental to understanding this ocean of data and form the primary input to many downstream analyses. A basic assumption of methods to infer genealogies from viral genetic data is that recombination is negligible and the genealogy is a tree. However, recombinant lineages have risen to global prevalence, and simple tree representations are therefore incomplete and potentially misleading. We present sc2ts, a method to infer reticulate genealogies as an Ancestral Recombination Graph (ARG) in real time at pandemic scale. We infer an ARG for 2.48 million SARS-CoV-2 genomes, which leverages the widely used tskit software ecosystem to support further analyses and visualisation. This rich and validated resource clarifies the relationships among recombinant lineages, quantifies the rate of recombination over time, and provides a lower bound on detectable recombination.

evolutionary biology↗

bioRxiv2023

Reply to Barton et al: signatures of natural selection during the Black Death

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2x10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

genomics↗

bioRxiv2022

Unravelling specific diet and gut microbial contributions to inflammatory bowel disease

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, Interleukin-10, we show that low dietary fiber promotes bacterial erosion of colonic mucus, leading to lethal colitis. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Diet-induced inflammation is driven by Th1 immune responses, which increase in the presence of mucin-degrading bacteria and are preceded by expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Inflammation occurs first in intestinal regions with thinner mucus. Our work underscores the importance of focusing on microbial functions--not taxa--contributing to IBDs and some diet-mediated functions block those that promote disease.

microbiology↗

bioRxiv2021

Spatial metabolomics reveals localized impact of influenza virus infection on the lung tissue metabolome

The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention, but are complicated by consideration of IAVs vast strain diversity, manufacturing and vaccine uptake limitations. While antivirals may be used for treatment of IAV, they are most effective in early stages of the infection and several virus strains have become drug resistant. Therefore, there is a need for advances in IAV treatment, especially host-directed, personalized therapeutics.Given the spatial dynamics of IAV infection and the relationship between viral spatial distribution and disease severity, a spatial approach is necessary to expand our understanding of IAV pathogenesis. We used spatial metabolomics to address this issue. Spatial metabolomics combines liquid chromatography-tandem mass spectrometry of metabolites extracted from systematic organ sections, 3D models and computational techniques, to develop spatial models of metabolite location and their role in organ function and disease pathogenesis. In this project, we analyzed plasma and systematically sectioned lung tissue samples from uninfected or infected mice. Spatial mapping of sites of metabolic perturbations revealed significantly lower metabolic perturbation in the trachea compared to other lung tissue sites. Using random forest machine learning, we identified metabolites that responded differently in each lung position based on infection, including specific amino acids, lipids and lipid-like molecules, and nucleosides. These results support the implementation of spatial metabolomics to understand metabolic changes upon IAV infection and to identify candidate pathways to be targeted for IAV therapeutics. ImportanceThe influenza virus is a major health concern. Over 1 billion people become infected annually despite the wide distribution of vaccines, and antiviral agents are insufficient to address current clinical needs. In this study, we used spatial metabolomics to understand changes in the lung and plasma metabolome of mice infected with influenza A virus, compared to uninfected controls. We determined metabolites altered by infection in specific lung tissue sites and distinguished metabolites perturbed by infection between lung tissue and plasma samples. Our findings highlight the importance of a spatial approach to understanding the intersection between lung metabolome, viral infection and disease severity. Ultimately, this approach will expand our understanding of respiratory disease pathogenesis and guide the development of novel host-directed therapeutics.

microbiology↗

bioRxiv2021

Mcc1229, an Stx2a-amplifying microcin, is produced in vivo and requires CirA for activity

Enterohemorrhagic E. coli (EHEC) strains, including the foodborne pathogen E. coli O157:H7, are responsible for thousands of hospitalizations each year. Various environmental triggers can modulate pathogenicity in EHEC by inducing expression of Shiga toxin (Stx), which is encoded on a lambdoid prophage and transcribed together with phage late genes. Cell-free supernatants of the sequence type (ST) 73 E. coli strain 0.1229 are potent inducers of Stx2a production in EHEC, suggesting that 0.1229 secretes a factor that activates the SOS response and leads to phage lysis. We previously demonstrated that this factor, designated microcin (Mcc) 1229, was proteinaceous and plasmid-encoded. To further characterize Mcc1229 and support its classification as a microcin, we investigated its regulation, determined its receptor, and identified loci providing immunity. Production of Mcc1229 was increased upon iron limitation, as determined by ELISA, lacZ fusions, and qRT-PCR. Spontaneous Mcc1229-resistant mutants and targeted gene deletion revealed that CirA was the Mcc1229 receptor. TonB, which interacts with CirA in the periplasm, was also essential for Mcc1229 import. Subcloning of the Mcc1229 plasmid indicated that Mcc activity was neutralized by two ORFs, each predicted to encode a domain of unknown function (DUF)-containing protein. In a germfree mouse model of infection, colonization with 0.1229 suppressed subsequent colonization of EHEC. Although Mcc1229 was produced in vivo, it was dispensable for colonization suppression. The regulation, import, and immunity determinants identified here are consistent with features of other Mccs, suggesting that Mcc1229 be included in this class of small molecules.

microbiology↗

bioRxiv2021

Fetal maturation revealed by amniotic fluid cell-free transcriptome in rhesus macaques

Accurate estimate of fetal maturity could provide individualized guidance for delivery of complicated pregnancies. However, current methods are invasive, have low accuracy, and are limited to fetal lung maturation. To identify diagnostic gestational biomarkers, we performed transcriptomic profiling of lung and brain, as well as cell-free RNA from amniotic fluid of preterm and term rhesus macaque fetuses. These data predict new and prior associated gestational age differences in distinct lung and neuronal cell populations when compared to existing single-cell and bulk RNA-Seq data. Comparative analyses found over 200 genes coincidently induced in lung and amniotic fluid, and dozens in brain and amniotic fluid. This data enabled creation of computational models that accurately predicted lung compliance from amniotic fluid and lung transcriptome of preterm fetuses treated with antenatal corticosteroids. Cell-free RNA in amniotic fluid may provide a substrate of global fetal maturation markers for personalized management of at-risk pregnancies.

systems biology↗

bioRxiv2019

A rare opportunist, Morganella morganii, decreases severity of polymicrobial catheter-associated urinary tract infection

Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. Proteus mirabilis is one of the most common causes of monomicrobial and polymicrobial CAUTI, and frequently co-colonizes with Enterococcus faecalis, Escherichia coli, Providencia stuartii, and Morganella morganii. P. mirabilis infections are particularly challenging due to its potent urease enzyme, which facilitates formations of struvite crystals, catheter encrustation, blockage, and formation of urinary stones. We previously determined that interactions between P. mirabilis and other uropathogens can enhance P. mirabilis urease activity, resulting in greater disease severity during experimental polymicrobial infection. Our present work reveals that M. morganii acts on P. mirabilis in a contact-independent manner to decrease urease activity. Furthermore, M. morganii actively prevents urease enhancement by E. faecalis, P. stuartii, and E. coli. Importantly, these interactions translate to modulation of disease severity during experimental CAUTI, predominantly through a urease-dependent mechanism. Thus, products secreted by multiple bacterial species in the milieu of the catheterized urinary tract can directly impact prognosis.

microbiology↗