Proteomics of the heart

Physiological Reviews, Год журнала: 2024, Номер 104(3), С. 931 - 982

Опубликована: Фев. 1, 2024

Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at molecular level. Proteomics provides biologists with snapshot of context-dependent and proteoform expression, structural conformations, dynamic turnover, protein-protein interactions. Cardiac can offer broader deeper understanding the mechanisms that underscore cardiovascular disease, it foundational to development future therapeutic interventions. This review encapsulates evolution, current technologies, perspectives proteomic-based mass spectrometry as applies study heart. Key technological advancements have allowed researchers proteomes single-cell level employ robot-assisted automation systems for enhanced sample preparation techniques, increase fidelity spectrometers has unambiguous numerous posttranslational modifications. Animal models ranging from early animal experiments heart failure preserved ejection fraction, provided tools challenging organ laboratory. Further will pave way implementation even closer within clinical setting, allowing not only scientists but also patients benefit an interplay relates cardiac disease physiology.

Язык: Английский

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In Situ Metal–Organic Framework Growth in Serum Encapsulates and Depletes Abundant Proteins for Integrated Plasma Proteomics

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Protein biomarkers in human serum provide critical insights into various physiological conditions and diseases, enabling early diagnosis, prognosis, personalized treatment. However, detecting low-abundance protein is challenging due to the presence of highly abundant proteins that make up ∼99% plasma proteome. Here, we report use situ metal–organic framework (MOF) growth effectively deplete for integrated proteomic analysis. Through biomolecule-mediated nucleation a zeolitic imidazolate (ZIF-8), are selectively encapsulated within ZIF-8 removed from via centrifugation, leaving depleted fraction supernatant. Bottom-up proteomics analysis confirmed significant depletion topmost proteins, many at levels exceeding 95%. Such enabled identification 277 total supernatant (uncaptured) single-shot analysis, including 54 were only identified after depletion, 12 drug targets, potential disease biomarkers. Top-down characterization captured uncaptured fractions proteoform-level this method not biased toward any specific proteoform individual proteins. These results demonstrate MOF can high-abundance simple, low cost, one-pot synthesis enable top-down bottom-up

Язык: Английский

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TMT-based Multiplexed (Chemo)proteomics on the Orbitrap Astral Mass Spectrometer

Molecular & Cellular Proteomics, Год журнала: 2025, Номер unknown, С. 100968 - 100968

Опубликована: Апрель 1, 2025

Ongoing advancements in instrumentation has established mass spectrometry (MS) as an essential tool proteomics research and drug discovery. The newly released Asymmetric Track Lossless (Astral) analyzer represents a major step forward MS instrumentation. Here, we evaluate the Orbitrap Astral spectrometer context of tandem tag-based multiplexed activity-based proteome profiling, highlighting its sensitivity boost relative to Tribrid platform-50% at peptide 20% protein level. We compare TMT DDA label-free DIA on same instrument, both which quantify over 10,000 human proteins per sample within one hour. offers higher quantitative precision data completeness, while is free ratio compression thereby more accurate. Our results suggest that prevalent with high-resolution MS2-based quantification Astral, real-time search-based MS3 platform effectively restores accuracy. Additionally, benchmark TMT-based profiling by interrogating cysteine ligandability. measures 30,000 cysteines single-shot experiment, 54% increase Eclipse. further leverage this remarkable profile target engagement landscape FDA-approved covalent drugs, including Sotorasib Adagrasib. herein provide reference for optimal use advanced platform.

Язык: Английский

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Standard operating procedure combined with comprehensive quality control system for multiple LC-MS platforms urinary proteomics

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 26, 2025

Abstract Urinary proteomics is emerging as a potent tool for detecting sensitive and non-invasive biomarkers. At present, the comparability of urinary data across diverse liquid chromatography−mass spectrometry (LC-MS) platforms remains an area that requires investigation. In this study, we conduct comprehensive evaluation proteome multiple LC-MS platforms. To systematically analyze assess quality large-scale data, develop control (QC) system named MSCohort, which extracted 81 metrics individual experiment whole cohort evaluation. Additionally, present standard operating procedure (SOP) high-throughput analysis based on MSCohort QC system. Our study involves 20 reveals that, when combined with unified SOP, generated by data-independent acquisition (DIA) workflow in urine samples exhibit high robustness, sensitivity, reproducibility Furthermore, apply SOP to hybrid benchmarking clinical colorectal cancer (CRC) including 527 experiments. Across three different platforms, analyses report quantitative consistent disease patterns. This work lays groundwork studies spanning paving way precision medicine research.

Язык: Английский

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Honeybee proteinns in Saudi honeys: A shotgun gel-free proteomic study

Food Chemistry X, Год журнала: 2025, Номер 26, С. 102216 - 102216

Опубликована: Фев. 1, 2025

Язык: Английский

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Topology-Driven Discovery of Transmembrane Protein S-Palmitoylation

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108259 - 108259

Опубликована: Фев. 1, 2025

Protein S-palmitoylation is a reversible lipophilic posttranslational modification regulating diverse number of signaling pathways. Within transmembrane proteins (TMPs), implicated in conditions from inflammatory disorders to respiratory viral infections. Many small-scale experiments have observed at juxtamembrane Cys residues. However, most large-scale S-palmitoyl discovery efforts rely on trypsin-based proteomics within which hydrophobic regions are likely underrepresented. Machine learning- by virtue its freedom experimental constraints - particularly well suited address this gap surrounding TMP S-palmitoylation. Utilizing UniProt-derived feature set, gradient boosted machine learning tool (TopoPalmTree) was constructed and applied holdout dataset S-palmitoylated proteins. Upon application the mouse proteome, 1591 putative sites (i.e. not listed SwissPalm or UniProt) were identified. Two lung-expressed candidates (synaptobrevin Vamp5 water channel Aquaporin-5) experimentally assessed, as 3 Type I (Cadm4, Chodl Havcr2). Finally, TopoPalmTree used for rational design an site KDEL-Receptor 2. This readily interpretable model aligns innumerable observing into proteomic design, thus facilitating future investigations important modification.

Язык: Английский

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Comparative Proteomics of Salinity Stress Responses in Fish and Aquatic Invertebrates

PROTEOMICS, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Fluctuating salinity is symptomatic of climate change challenging aquatic species. The melting polar ice, rising sea levels, coastal surface and groundwater salinization, increased evaporation in arid habitats alter worldwide. Moreover, the frequency intensity extreme weather events such as rainstorms floods increase, causing rapid shifts brackish habitat salinity. Such alterations disrupt homeostasis ultimately diminish fitness, organisms by interfering with metabolism, reproduction, immunity, other critical aspects physiology. Proteins are central to these physiological mechanisms. They represent molecular building blocks phenotypes that govern organismal responses environmental challenges. Environmental cues regulate proteins a concerted fashion, necessitating holistic analyses proteomes for comprehending stress responses. Proteomics approaches reveal causes population declines enable bioindication geared toward timely interventions prevent local extinctions. effects on have been performed since mid-1990s, propelled invention two-dimensional protein gels, soft ionization techniques mass spectrometry (MS), nano-liquid chromatography 1970s 1980s. This review summarizes current knowledge regulation from organisms, including key methodological advances over past decades.

Язык: Английский

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Recent Advances in Mass Spectrometry-Based Bottom-Up Proteomics

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Mass spectrometry-based proteomics is about 35 years old, and recent progress appears to be speeding up across all subfields. In this review, we focus on advances over the last two in select areas within bottom-up proteomics, including approaches high-throughput experiments, data analysis using machine learning, drug discovery, glycoproteomics, extracellular vesicle structural proteomics.

Язык: Английский

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MSConnect: Open-Source, End-to-End Platform for Automated Mass Spectrometry Data Management, Analysis, and Visualization

Journal of Proteome Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

The scale of mass spectrometry-based proteomics data sets continues to increase, and the analysis workflows are becoming more complex as various steps carried out using a multitude software programs developed by both commercial providers research community. Manually shepherding across multiple in-house-developed scripts can be error prone labor intensive. It is also difficult for others follow same steps, leading poor repeatability. We have an integrated management platform termed MSConnect that enables simple traceable processing programs, thus improving repeatability automating common backup from point collection through summarization visualization. open nature diverse omics community seamlessly integrate third-party tools or develop automate their own unique workflows. With license design architecture, has potential become community-driven serving wide range MS-based researchers.

Язык: Английский

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Top-Down Proteomic Profiling of Protein Corona by High-Throughput Capillary Isoelectric Focusing-Mass Spectrometry

Journal of the American Society for Mass Spectrometry, Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

In the rapidly evolving field of nanomedicine, understanding interactions between nanoparticles (NPs) and biological systems is crucial. A pivotal aspect these formation a protein corona when NPs are exposed to fluids (e.g., human plasma), which significantly influences their behavior functionality. This study introduces an advanced capillary isoelectric focusing tandem mass spectrometry (cIEF-MS/MS) platform designed enable high-throughput reproducible top-down proteomic analysis corona. Our cIEF-MS/MS technique completed each within 30 min. It produced proteoform measurements for at least 50 runs regarding proteoforms' migration time [relative standard deviations (RSDs) <4%], intensity (Pearson's correlation coefficients any two >0.90), number identifications (71 ± 10), proteoform-spectrum matches (PrSMs) (196 30). Of 53 identified genes, 33 potential biomarkers various diseases cancer, cardiovascular disease, Alzheimer's disease). We 1-102 proteoforms per biomarker, containing sequence variations or post-translational modifications. Delineating in by our fashion will benefit nanobiointeractions advance both diagnostic therapeutic nanomedicine technologies.

Язык: Английский

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