Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation. DOI Open Access
Mariana Gomes da Silva Araujo,

Aurèlie Sallé,

Vincent Cahais

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

ABSTRACT Background Epigenetic regulator genes play critical roles in controlling cell identity and are frequently disrupted breast cancers, suggesting a key driver role this disease its associated phenotypes. However, specific epigenetic drivers (epidrivers) of mammary plasticity their mechanistic contributions to phenotype poorly characterized. Methods To identify potential epidrivers the emergence mesenchymal cancer stem cell-like phenotypes non-tumorigenic cells, we employed CRISPR/Cas9 loss-of-function screening strategy targeting genes. This approach was followed by an in-depth validation characterization epigenomic, transcriptomic, proteomic phenotypic changes resulting from disruption putative epidriver gene BAP1 . Results Our investigation revealed that loss histone deubiquitinase impacts cellular processes with such as epithelial-to-mesenchymal transition (EMT) actin cytoskeleton organization. In addition, unveiled resulted overall less permissive chromatin downregulated expression, impacting programs control glycosylation leading decreased glycan abundance complexity. rescue restored expression several deregulated catalytic activity-dependent manner, BAP1-mediated regulation largely dependent on activity. Conclusions Overall, our results point reveal novel glycosylation.

Language: Английский

diaTracer enables spectrum-centric analysis of diaPASEF proteomics data DOI Creative Commons
Kai Li, Guo Ci Teo, Kevin Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract Data-independent acquisition has become a widely used strategy for peptide and protein quantification in liquid chromatography-tandem mass spectrometry-based proteomics studies. The integration of ion mobility separation into data-independent analysis, such as the diaPASEF technology available on Bruker’s timsTOF platform, further improves accuracy depth achievable using acquisition. We introduce diaTracer, spectrum-centric computational tool optimized data. diaTracer performs three-dimensional (mass to charge ratio, retention time, mobility) peak tracing feature detection generate precursor-resolved “pseudo-tandem spectra”, facilitating direct (“spectral-library free”) identification from is stand-alone fully integrated FragPipe platform. demonstrate performance data triple-negative breast cancer, cerebrospinal fluid, plasma samples, phosphoproteomics human leukocyte antigens immunopeptidomics experiments, low-input spatial study. also show that enables unrestricted post-translational modifications open/mass-offset searches.

Language: Английский

Citations

3
Spaceflight alters protein levels and gene expression associated with stress response and metabolic characteristics in human cardiac spheroids DOI
Parvin Forghani, Wenhao Liu, Zeyu Wang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123080 - 123080

Published: Jan. 7, 2025

Language: Английский

Citations

0
prolfquapp ─ A User-Friendly Command-Line Tool Simplifying Differential Expression Analysis in Quantitative Proteomics DOI Creative Commons
Witold Wolski, Jonas Grossmann, Leonardo Schwarz

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Mass spectrometry is a cornerstone of quantitative proteomics, enabling relative protein quantification and differential expression analysis (DEA) proteins. As experiments grow in complexity, involving more samples, groups, identified proteins, interactive tools become impractical. The prolfquapp addresses this challenge by providing command-line interface that simplifies DEA, making it accessible to nonprogrammers seamlessly integrating into workflow management systems. Prolfquapp streamlines data processing result visualization generating dynamic HTML reports facilitate the exploration results. These allow for investigating complex experiments, such as those repeated measurements or multiple explanatory variables. Additionally, supports various output formats, including XLSX files, SummarizedExperiment objects rank further using spreadsheet software, exploreDE Shiny application, gene set enrichment respectively. By leveraging advanced statistical models from prolfqua R package, offers user-friendly, integrated solution large-scale proteomics studies, combining efficient with insightful, publication-ready outputs.

Language: Английский

Citations

0
A Platform for Engineering Tissue Membranes from Cell Spheroids DOI Creative Commons
Bach Quang Le, Hariharan Ezhilarasu, Weng Wan Chan

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101526 - 101526

Published: Jan. 31, 2025

Language: Английский

Citations

0
Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration DOI Creative Commons
Christabel Thembela Dube, Hamish T. J. Gilbert,

Niamh Rabbitte

et al.

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: Feb. 10, 2025

Abstract Background Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in tissue extracellular matrix (ECM) progresses. Improved techniques, combination blood biomarkers, are needed monitor progression for more effective treatment plans. Methods To identify biomarkers associated progression, we histologically graded 35 adult human degenerate tissues matched plasma from individuals into two groups: mild severe degenerate. Mass spectrometry was utilised characterise proteomic differences between groups. Top differentially distributed proteins were further validated using immunohistochemistry qRT-PCR. Additionally, correlational analyses conducted define similarities protein degeneration. Results Our data revealed that abundance 31 significantly increased degenerated compared mild. Functional showed than 40% these matrisome-related, indicating ECM composition tissues. We confirmed adipocyte enhancer-binding 1 (AEBP1) one enriched core matrisome genes progressed. Compared others, AEBP1 levels best distinguished an area under curve score 0.768 (95% CI: 0.60–0.93). However, found exhibited weak relationship histological grading levels. Given systemic complex, larger sample cohort may be required patterns relating progression. Conclusions In this study, have identified marker monitoring severity humans. Further work link alterations blood-related will beneficial detailed thereby enabling personalised approaches.

Language: Английский

Citations

0
What have Data Standards ever done for us? DOI Creative Commons
Sandra Orchard

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100933 - 100933

Published: Feb. 1, 2025

Language: Английский

Citations

0
Sympathetic nociceptive afferent signaling drives the chronic structural and functional autonomic remodeling after myocardial infarction DOI Open Access

Valerie Van Weperen,

Jonathan D. Hoang,

Neil Jani

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

ABSTRACT After myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, occurs predisposes to ventricular arrhythmias (VT/VF). The underlying factors that drive this the observed neuroinflammation glial activation, remain unknown. We hypothesized sympathetic nociceptive afferents underlie remodeling post-MI. Epidural resiniferatoxin (RTX, ablate cardiac afferent neurons) vs. saline was administered in pigs prior MI electrophysiological effects assessed four six weeks post-infarction. Acute of ablation after chronic were also a separate group animals. Baroreflex sensitivity tone, as measured by parasympathetic neuronal activity responses, improved infarcted animals which received epidural RTX MI. These demonstrated reduced spinal cord inflammation downregulation circulating stress inflammatory pathways, stabilization parameters, with VT/VF-inducibility. acutely restored function decreased VT/VF. data suggest directly contribute VT/VF susceptibility MI-induced oxidative stress, inflammation, function, providing novel insights into causal role these driving sympathovagal imbalance

Language: Английский

Citations

0
Sympathetic nociceptive afferent signaling drives the chronic structural and functional autonomic remodeling after myocardial infarction DOI Creative Commons
Marmar Vaseghi,

Valerie van Weperen,

Jonathan D. Hoang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract After myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, occurs predisposes to ventricular arrhythmias (VT/VF). The underlying factors that drive this the observed neuroinflammation glial activation, remain unknown. We hypothesized sympathetic nociceptive afferents underlie remodeling post-MI. Epidural resiniferatoxin (RTX, ablate cardiac afferent neurons) vs. saline was administered in pigs prior MI electrophysiological effects assessed four six weeks post-infarction. Acute of ablation after chronic were also a separate group animals. Baroreflex sensitivity tone, as measured by parasympathetic neuronal activity responses, improved infarcted animals which received epidural RTX MI. These demonstrated reduced spinal cord inflammation downregulation circulating stress inflammatory pathways, stabilization parameters, with VT/VF-inducibility. acutely restored function decreased VT/VF. data suggest directly contribute VT/VF susceptibility MI-induced oxidative stress, inflammation, function, providing novel insights into causal role these driving sympathovagal imbalance

Language: Английский

Citations

0
MSFragger-DDA+ enhances peptide identification sensitivity with full isolation window search DOI Creative Commons
Fengchao Yu, Yamei Deng, Alexey I. Nesvizhskii

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 8, 2025

Abstract Liquid chromatography-mass spectrometry based proteomics, particularly in the bottom-up approach, relies on digestion of proteins into peptides for subsequent separation and analysis. The most prevalent method identifying from data-dependent acquisition mass data is database search. Traditional tools typically focus a single peptide per tandem spectrum, often neglecting frequent occurrence co-fragmentations leading to chimeric spectra. Here, we introduce MSFragger-DDA+, search algorithm that enhances identification by detecting co-fragmented with high sensitivity speed. Utilizing MSFragger’s fragment ion indexing algorithm, MSFragger-DDA+ performs comprehensive within full isolation window each followed robust feature detection, filtering, rescoring procedures refine results. Evaluation against established across diverse datasets demonstrated that, integrated FragPipe computational platform, significantly increases while maintaining stringent false discovery rate control. It also uniquely suited wide-window data. provides an efficient accurate solution identification, enhancing detection low-abundance peptides. Coupled enables more analysis proteomics

Language: Английский

Citations

0
Recent implementations of data-independent acquisition for cancer biomarker discovery in biological fluids DOI Creative Commons
Annie Ha, Michael Woolman, Matthew Waas

et al.

Expert Review of Proteomics, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Cancer is the second leading cause of death worldwide and accurate biomarkers for early detection disease monitoring are needed to improve outcomes. Biological fluids, such as blood urine, ideal samples biomarker measurements they can be routinely collected with relatively minimally invasive methods. However, proteomics analysis fluids has been a challenge due high dynamic range its protein content. Advances in data-independent acquisition (DIA) mass spectrometry-based address some technical challenges biofluids, thus enabling ability spectrometry propel large-scale discovery. We reviewed principles DIA recent applications cancer discovery using biofluids. summarized studies biological context research over past decade, provided comprehensive overview benefits DIA-MS. Various showed potential DIA-MS identifying putative high-throughput manner. lack proper study design standardization methods across platforms still need addressed fully utilize accelerate verification processes.

Language: Английский

Citations

0