Biology subjects

Meehan, M. J.

Publications and source records attributed to Meehan, M. J..

6 recordsLinked to original sources

bioRxiv2024

The microbiome diversifies N-acyl lipid pools - including short-chain fatty acid-derived compounds

N-acyl lipids are important mediators of several biological processes including immune function and stress response. To enhance the detection of N-acyl lipids with untargeted mass spectrometry-based metabolomics, we created a reference spectral library retrieving N-acyl lipid patterns from 2,700 public datasets, identifying 851 N-acyl lipids that were detected 356,542 times. 777 are not documented in lipid structural databases, with 18% of these derived from short-chain fatty acids and found in the digestive tract and other organs. Their levels varied with diet, microbial colonization, and in people living with diabetes. We used the library to link microbial N-acyl lipids, including histamine and polyamine conjugates, to HIV status and cognitive impairment. This resource will enhance the annotation of these compounds in future studies to further the understanding of their roles in health and disease and highlight the value of large-scale untargeted metabolomics data for metabolite discovery.

bioinformatics↗

bioRxiv2023

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms role in ecology and human health.

microbiology↗

bioRxiv2022

Open Access Repository-Scale Propagated Nearest Neighbor Suspect Spectral Library for Untargeted Metabolomics

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of public MS/MS spectra. Annotations were propagated based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimers brain phenotype. The nearest neighbor suspect spectral library is openly available through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

bioinformatics↗

bioRxiv2020

Profiling the effect of nafcillin on HA-MRSA D592 using bacteriological and physiological media

Staphylococcus aureus is a leading human pathogen associated with both hospital-acquired and community-acquired infections. The bacterium has steadily gained resistance to {beta}-lactams and other important first-line antibiotics culminating in its categorization as an urgent threat by the U.S. Centers for Disease Control and Prevention. Observations of a varying response to antimicrobial exposure as a function of media type has revealed that clinical susceptibility testing performed in standard bacteriological media might not adequately represent pharmacological responses in the patient. Such observations have encouraged research designed to identify media types that more closely mimic the in vivo environment. In this study, we examine the response of a hospital-acquired USA100 lineage methicillin-resistant, vancomycin-intermediate S. aureus (MRSA/VISA) strain (D592) to nafcillin in a bacteriological compared to a more physiological tissue culture-based medium. We performed multi-dimensional analysis including growth and bacterial cytological profiling, RNA sequencing, and exo-metabolomics measurements (both HPLC and LC/MS) to shed light on the media-dependent activity of the commonly prescribed {beta}-lactam antibiotic nafcillin. O_TBL View this table: org.highwire.dtl.DTLVardef@85b95borg.highwire.dtl.DTLVardef@14c1504org.highwire.dtl.DTLVardef@1f7e976org.highwire.dtl.DTLVardef@100598dorg.highwire.dtl.DTLVardef@1f770e9_HPS_FORMAT_FIGEXP M_TBL C_TBL

microbiology↗

bioRxiv2019

Repository-scale Co- and Re-analysis of Tandem Mass Spectrometry Data

Metabolomics data are difficult to find and reuse, even in public repositories. We, therefore, developed the Reanalysis of Data User (ReDU) interface (https://redu.ucsd.edu/), a community- and data-driven approach that solves this problem at the repository scale. ReDU enables public data discovery and co- or re-analysis via uniformly formatted, publicly available MS/MS data and metadata in the Global Natural Product Social Molecular Networking Platform (GNPS), consistent with findable, accessible, interoperable, and reusable (FAIR) principles.1

bioinformatics↗

bioRxiv2019

Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia1. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition, but we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes2. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host lipids; such as sphingolipids and bile acids3-11. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. Considering the diversity of the human microbiome, numbering over 40,000 operational taxonomic units12, a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model13-15 to provide an untargeted assessment of the chemical diversity between germ-free (GF) and colonized mice (specific-pathogen free, SPF), and report the finding of novel bile acids produced by the microbiome in both mice and humans that have evaded characterization despite 170 years of research on bile acid chemistry16.

microbiology↗