Biology subjects

Plubell, D.

Publications and source records attributed to Plubell, D..

5 recordsLinked to original sources

bioRxiv2026

Serum proteomics reveals distinct phenotypic signatures to IL-6 blockade between two immunotherapies

A recent clinical study tested the effects of two different monoclonal antibodies (mAbs) (siltuximab, anti-IL6; tocilizumab, anti-IL6R) on the fate and function of T-cells in people with type 1 diabetes. While both mAbs affect the response of T-cells to stimulation, they have very different, sometimes opposing mechanisms. Here, we use mass-spectrometry based proteomics to analyze longitudinal serum samples (baseline and two weeks post-treatment) from 20 clinical trial participants to examine the effects of siltuximab and tocilizumab on extracellular vesicles. To accomplish this, serum samples were enriched for extracellular vesicles with Mag-Net and analyzed by LC-MS/MS to identify significantly differentially abundant protein groups and pathways. Proteome analysis confirmed highly reproducible measurements across multiple draw dates. In total, we quantified >3300 protein groups of which 46 protein groups had significantly altered abundance after mAb treatment. Tocilizumab altered pathways associated with proteostasis (neddylation) and pre-notch transcription and translation. Siltuximab altered FCGR activation pathway members. In addition, quantitation of the monoclonal antibody therapies themselves enabled the measurement of the correlation between drug amounts and impacted proteins. Taken together, this work demonstrates the utility of the Mag-Net method to evaluate the impacts of therapeutic interventions on serum extracellular vesicles.

biochemistry↗

bioRxiv2025

Evaluation of an Orbitrap Astral Zoom mass spectrometer prototype for quantitative proteomics - beyond identification lists

Mass spectrometry instrumentation continues to evolve rapidly yet quantifying these advances beyond conventional peptide and protein detections remain challenging. Here, we evaluate a modified Orbitrap Astral Zoom mass spectrometer (MS) prototype and compare its performance to the standard Orbitrap Astral MS. Across a range of acquisition methods and sample inputs, the prototype instrument outperformed the standard Orbitrap Astral MS in precursor and protein identifications, ion beam utilization, and quantitative precision. To enable meaningful cross-platform comparisons, we implemented an ion calibration framework that converts signal intensity from arbitrary units to ion per second. This benchmarking strategy showed that the prototype sampled 30% more ions per peptide than the original Orbitrap Astral MS. This increase in the ion beam utilization resulted in improved sensitivity and quantitative precision. To make these metrics broadly accessible, we added new metrics to the Skyline document grid to report the number of ions measured in a spectrum at the apex of the elution peak or the sum of ions between the peak integration boundaries. Taken together, our results demonstrate the prototype Orbitrap Astral Zoom as a high-performance platform for DIA proteomics and establish a generalizable framework for evaluation of mass spectrometer performance based on the number of ions detected for each analyte. Data are available on Panorama Public and on ProteomeXchange under the identifier PXD064536.

biochemistry↗

bioRxiv2024

Microbial Metagenomes Across a Complete Phytoplankton Bloom Cycle:High-Resolution Sampling Every 4 Hours Over 22 Days

In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22-1.2 {micro}m), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms.

ecology↗

bioRxiv2022

A Peptide-Centric Quantitative Proteomics Dataset for the Phenotypic Assessment of Alzheimer's Disease

Alzheimers disease (AD) is a looming public health disaster with limited interventions. Alzheimers is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain tissue was preserved postmortem by rapid autopsy. Samples from four brain regions were processed and analyzed by data-independent acquisition LC-MS/MS. Here we present a high-quality quantitative dataset at the peptide and protein level for each brain region. Multiple internal and external control strategies were included in this experiment to ensure data quality. All data are deposited in the ProteomeXchange repositories and available from each step of our processing.

neuroscience↗

bioRxiv2022

Proteomics of resilience to Alzheimer's disease identifies brain regional soluble Aβ levels, actin filament processes, and response to injury

Resilience to Alzheimers disease (RAD) is an uncommon combination of high disease burden without dementia that may provide critical insights into limiting the clinical impact of this incurable disease. In this study, we used mass spectrometry-based proteomics to quantify regional protein differences that characterize RAD. Starting with over 700 brain donations, we identified 43 extensively annotated research participants who met stringent inclusion exclusion criteria and analyzed matched isocortical regions, hippocampus, and caudate nucleus. Differential expression analysis of 7,115 soluble proteins identified lower isocortical and hippocampal soluble A{beta} peptide levels as a significant feature of RAD. Protein co-expression analysis revealed a group of 181 densely-interacting proteins significantly associated with RAD that were enriched for actin filament-based process, cellular detoxification, and wound healing in isocortex and hippocampus. We further support our findings using data from 689 human isocortical samples from four independent external cohorts that were the closest approximations of our clinico-pathologic groups. The molecular basis of RAD, a widely replicated state in older adults for which there is no experimental model, likely holds important insights into therapeutic interventions for Alzheimers disease.

neuroscience↗