Biology subjects

Aron, A.

Publications and source records attributed to Aron, A..

6 recordsLinked to original sources

bioRxiv2026

The Everything Bagel Feature Finder: Ultra-fast automated feature finding for untargeted metabolomics

Metabolomics studies are increasingly being applied with hundreds to thousands, even tens of thousands of samples that demand rapid, automated data processing while maintaining analytical sensitivity or quantitative accuracy. A major computational bottleneck is feature finding, which is the transformation of LC-MS and LC-MS/MS data into a set of analyte signals aligned and quantified across samples. Feature finding can be computationally intensive and often requires manual iterative parameter optimization. To accelerate this process, we present the Everything Bagel (EB) feature finder, an ultra-fast automated feature finding tool that integrates feature detection, retention-time alignment, and gap filling designed for run-time and memory efficiency. We benchmarked EB against two automated feature finding methods on eight benchmarking datasets. Specifically, we evaluated these three feature finding methods by measuring spike-in standard detection coverage, dilution series quantification accuracy, and yeast 12C/13C credentialed features. In this evaluation, the EB feature finder achieved performance comparable to, and often exceeding, existing methods while requiring up to 150-fold lower CPU hours and up to 113-fold lower wall time. We further demonstrated the bioanalytical validity of EB by reanalyzing published datasets used for biomarker discovery and reproduced biologically significant features that matched the published findings using manually tuned feature finding settings. Taken along with the speed improvements, we anticipate EB will enhance the ability to automatically analyze datasets with thousands to tens of thousands of samples for the community.

bioinformatics↗

bioRxiv2026

Bacteroides fragilis modulates gut microbiome community composition, frontal cortex gene expression, and fecal and frontal cortex metabolites in a mouse model of Alzheimers disease pathologies

Alzheimers disease (AD) is a neurodegenerative disease and the leading cause of dementia among elderly. Gut microbiome alterations precede pathogenesis and may affect disease outcomes. We evaluated the role of Bacteroides fragilis in triple transgenic mice modeling AD pathologies (3xTg-AD) and wild-type controls (WT). Subsets of 3xTg-AD and WT mice were longitudinally treated with B. fragilis or sterile vehicle control for five consecutive days at 8 weeks of age and then monthly up to 52-56 weeks. Fecal samples were collected fortnightly from 8 through 52-56 weeks of age. Mice were sacrificed at 8 (baseline), 24 (amyloid-{beta} plaques modeled), and 52-56 (amyloid-{beta} plaques and neurofibrillary tangles modeled) weeks of age. Expression of genes involved in neuroinflammation and neurotransmission were quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Fecal bacterial microbiota were assessed by sequencing the V4 region of the 16S rRNA gene, and microbiome sequence data were analyzed using QIIME 2. Frontal cortex and fecal metabolomes were evaluated using LC-MS/MS. We observed that B. fragilis colonized the gut microbiota of 3xTg-AD mice earlier and more consistently than WT mice. 3xTg-AD mice treated with B. fragilis demonstrate lower gene expression of GFAP, SLC1A3, and FOXO3 in the frontal cortex. Consistent with this finding, treatment with B. fragilis restores levels of amino acid derivatives and neurotransmitters in 3xTg-AD mice to resemble levels in WT mice. These results highlight the role of the gut microbiome in AD-associated neuroinflammation and neurotransmission and the need for future studies to elucidate the mechanisms underlying these changes. ImportancePrevious studies in animals modeling Alzheimers disease pathologies and humans living with Alzheimers disease demonstrate shifts in the gut microbial community composition prior to and concomitant with pathological onset. The bacterial genus, Bacteroides, is commonly found differentially abundant in these studies but its effects on disease outcomes are poorly understood. In this study, we explore the effects of chronic exposure to Bacteroides fragilis in triple transgenic mice modeling Alzheimers disease pathologies and healthy, wild-type controls. We observed changes in microbial community composition in mice modeling Alzheimers disease when treated with B. fragilis, and associated changes in neuroinflammation, biomarkers of neurotransmission, and the brain metabolome. Taken together, these results suggest that Bacteroides fragilis exerts neuromodulatory effects that may be beneficial in Alzheimers disease.

microbiology↗

bioRxiv2026

Discovery of metallophore diversity in Microbulbifer in mixed culture with a coral pathogen using computational mass spectrometry and genome mining

Iron is an essential component of cellular biology. Thus, irons low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is an underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language (MassQL) code to determine siderophore production by Microbulbifer spp. in mono- and mixed culture with a marine pathogen, which can be replicated for discovery of these compounds in any organism. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. This observation suggests that Microbulbifer uses alternate strategies in a mixed community, such as siderophore piracy for metal acquisition. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.

biochemistry↗

bioRxiv2026

A searchable metadata network graph for microbiome metabolomics

Establishing the biological context of microbial metabolites remains a major challenge. We present microbiomeMASST, a metadata-driven network graph that maps metabolites across 467 available datasets with 144,424 mass spectrometry files from humans, animals, and microbial culture systems. MicrobiomeMASST integrates monocultures, synthetic communities, and host-associated samples across multiple body sites and plants. MS/MS spectra can be queried to trace occurrence across hosts, experimental conditions, and interventions, enabling cross-study integration. We demonstrate this framework by contextualizing microbial-conjugated bile acids and interrogating microbiome-mediated drug metabolism. Screening gut bacteria revealed deprolylation of the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril. Using microbiomeMASST, we traced this metabolite across human cohorts, microbial isolates, environmental samples, and in Gorilla gorilla. Structural modeling and enzymatic assays showed that microbial deprolylation abolishes ACE inhibition, thereby inactivating its therapeutic effect. Together, microbiomeMASST links MS/MS spectra to biological context, converting isolated observations into an interpretable microbiome map for cross-study analysis.

biochemistry↗

bioRxiv2021

Sensory processing sensitivity and axonal microarchitecture: Identifying brain structural characteristics for behavior

Previously, researchers used functional MRI to identify regional brain activations associated with sensory processing sensitivity (SPS), a proposed normal phenotype trait. To further validate SPS as a behavioral entity, to characterize it anatomically, and to test the usefulness in psychology of methodologies that assess axonal properties, the present study correlated SPS proxy questionnaire scores (adjusted for neuroticism) with diffusion tensor imaging measures. Participants (n=408) from the Young Adult Human Connectome Project that are free of neurologic and psychiatric disorders were investigated. We computed mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA). A voxelwise, exploratory analysis showed that MD and RD correlated positively with SPS proxy scores in the right and left subcallosal and anterior ventral cingulum bundle, and the right forceps minor of the corpus callosum (peak Cohens D effect size = 0.269). Further analyses showed correlations throughout the entire right and left ventromedial prefrontal cortex, including the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate and arcuate fasciculus. These prefrontal regions are generally involved in emotion, reward and social processing. FA was negatively correlated with SPS proxy scores in white matter of the right premotor/motor/somatosensory/supramarginal gyrus regions, which are associated with empathy, theory of mind, primary and secondary somatosensory processing. Region of interest (ROI) analysis, based-on previous fMRI results and Freesurfer atlas-defined areas, showed small effect sizes, (+0.151 to -0.165) in white matter of the precuneus and inferior frontal gyrus. Other ROI effects were found in regions of the dorsal and ventral visual pathways and primary auditory cortex. The results reveal that in a large, diverse group of participants axonal microarchitectural differences can be identified with SPS traits that are subtle and in the range of typical behavior. The results suggest that the heightened sensory processing in people who show SPS may be influenced by the microstructure of white matter in specific neocortical regions. Although previous fMRI studies had identified most of these general neocortical regions, the DTI results put a new focus on brain areas related to attention and cognitive flexibility, empathy, emotion and low-level sensory processing, as in the primary sensory cortex. Psychological trait characterization may benefit from diffusion tensor imaging methodology by identifying influential brain systems for traits.

neuroscience↗

bioRxiv2020

Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut.

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. Unexpectedly, the probiotic bacterium Escherichia coli Nissle 1917 exhibited appreciable growth in zinc-limited media even when these transporters were deleted. By utilizing in vitro and in vivo studies, as well as native spray metal infusion mass spectrometry and ion identity molecular networking, we discovered that Nissle utilizes yersiniabactin as a zincophore. Indeed, yersiniabactin enables Nissle to scavenge zinc in zinc-limited media, to resist calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. Moreover, we discovered that yersiniabactins affinity for iron or zinc changes in a pH-dependent manner, with higher affinity for zinc as the pH increased. Altogether, we demonstrate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to many commensal and pathogenic Enterobacteriaceae.

microbiology↗