Biology subjects

McGovern, D. P. B.

Publications and source records attributed to McGovern, D. P. B..

3 recordsLinked to original sources

bioRxiv2025

Maternal IBD-related antibodies are associated with early life gut inflammatory status and microbiota composition: insights from cord blood

PurposeAntibodies in peripheral blood are used to aid in the diagnosis of inflammatory bowel disease (IBD), but their presence in neonatal cord blood and potential effects on early life development remain unknown. MethodsWe measured anti-CBir1, ANCA, anti-OmpC, ASCA IgA, and ASCA IgG levels in the cord blood of babies born to 78 mothers with or without IBD. Their association with fecal calprotectin (FC), and microbiota composition, characterized by 16S rRNA sequencing, was assessed throughout pregnancy and during the first 3 years of life using linear mixed-effects models. ResultsAntibodies were detected in cord blood, with significantly higher levels of anti-CBir1 and ASCA IgG in babies born to mothers with Crohns disease (p = 0.002) and higher abundance of ANCA and anti-OmpC in babies of mothers with ulcerative colitis (p = 0.002), compared to controls. ASCA IgG levels positively correlated with babies FC (p = 0.006), while babies microbiota Shannon diversity was negatively associated with ANCA, anti-OmpC, and ASCA IgA levels (p = 0.003, 0.04, and 0.008, respectively). Romboutsia spp., Citrobacter spp., Pseudomonas spp., Clostridiaceae, Clostridia, and Varibaculum spp. were positively correlated with either or both ANCA and anti-OmpC levels (all multiple testing adjusted q < 0.1). ConclusionOur findings suggest that maternal IBD-associated antibodies cross the placenta barrier and may be associated with intestinal inflammation and imbalanced microbiota colonization. Whether these serological profiles negatively influence the priming of the babys immune system or IBD risk later in life remains to be determined.

immunology↗

bioRxiv2025

Development and Clinical Evaluation of a Multiplexed Health Surveillance Panel Using Ultra High-Throughput PRM-MS in an Inflammatory Bowel Disease Cohort.

Despite advances in clinical proteomics, translating protein biomarker discoveries into clinical use remains challenging due to the technical complexity of the validation process. Targeted MS-based proteomics approaches such as parallel reaction monitoring (PRM) offer sensitive and specific assays for biomarker translation. In this study, we developed a multiplex PRM assay using the Stellar mass spectrometry platform to quantify 57 plasma proteins, including 21 FDA-approved proteins. Loading curves (11-points) were performed at 4 sample throughputs (100, 144, 180, and 300 samples per day) using independent, optimized, and scheduled PRM methods. Following optimization, an inflammatory bowel disease (IBD) cohort of plasma samples (493 IBD, 509 matched controls) was analyzed at a throughput of 180 SPD. To monitor system performance, the study also included 1,000 additional injections for system suitability tests, low-, middle-, and high-quality controls, washes, and blanks. Using this approach, we observed high quantifiability (linearity, sensitivity, reproducibility) in the PRM assay and consistent in data acquisition across a large cohort. We also validated the candidate IBD markers, C-reactive protein and orosomucoid protein, identified in a recent discovery experiment.

biochemistry↗

bioRxiv2024

Paradigm shift in biomarker translation: a pipeline to generate clinical grade biomarker candidates from DIA-MS discovery

Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package. This innovative tool uses the discovery cohort analysis to select precursors, peptides, and proteins that adhere to established targeted assay criteria. TEAQ was applied to Data-Independent Acquisition MS data from plasma samples acquired on an Orbitrap Astral MS. Identified precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra-protein correlation from 11-point loading curves under three throughputs, to develop a resource for clinical-grade targeted assays. From a clinical cohort of individuals with inflammatory bowel disease (n=492), TEAQ successfully identified 1116 signature peptides for 327 quantifiable proteins from 1180 identified proteins. Embedding stringent selection criteria adaptable to targeted assay development into the analysis of discovery data will streamline the transition to validation and clinical studies.

biochemistry↗