ArticleNature protocols2019
A comprehensive pipeline for translational top-down proteomics from a single blood draw.
Article in Nature protocols, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Quantitative Top-Down Proteomics Reveals Significant Differences in Histone Proteoforms Between Metastatic and Nonmetastatic Colorectal Cancer Cells.Proteomics · 2025Article
- Top-Down Proteomics: Why and When?Proteomics · 2025Article
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
- ResNeXt-Based Rescoring Model for Proteoform Characterization in Top-Down Mass Spectra.Interdisciplinary sciences, computational life sciences · 2025Article
- Sample preparation and cleanup methods for clinical top-down proteomics.Expert review of proteomics · 2025Review
- Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Spatial top-down proteomics for the functional characterization of human kidney.Clinical proteomics · 2025Article
- A Conformation-Specific Approach to Native Top-down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.Journal of proteome research · 2024Article
- Spatial top-down proteomics for the functional characterization of human kidney.bioRxiv : the preprint server for biology · 2024Article
- Multi Omics Applications in Biological Systems.Current issues in molecular biology · 2024Review
- Targeted Quantification of Proteoforms in Complex Samples by Proteoform Reaction Monitoring.Analytical chemistry · 2024Article
- Endotypes of Paediatric Cough-Do They Exist and Finding New Techniques to Improve Clinical Outcomes.Journal of clinical medicine · 2024Review
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Top-Down Proteomics and the Challenges of True Proteoform Characterization.Journal of proteome research · 2023Review
- Amyloid β Proteoforms Elucidated by Quantitative LC/MS in the 5xFAD Mouse Model of Alzheimer's Disease.Journal of proteome research · 2023Article
- A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer's Disease Diagnosis Using Targeted Proteomics and Machine Learning.International journal of molecular sciences · 2023Article
- Multi-Omics Studies in Historically Excluded Populations: The Road to Equity.Clinical pharmacology and therapeutics · 2023Review
- Spatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform.Molecular & cellular proteomics : MCP · 2023Article
- Mass Spectrometry-Based Proteomics Workflows in Cancer Research: The Relevance of Choosing the Right Steps.Cancers · 2023Review
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Authors and funding
7 authors.
Funding
Abstract
Top-down proteomics (TDP) by mass spectrometry (MS) is a technique by which intact proteins are analyzed. It has become increasingly popDesalting and concentrating GELFrEEular in translational research because of the value of characterizing distinct proteoforms of intact proteins. Compared to bottom-up proteomics (BUP) strategies, which measure digested peptide mixtures, TDP provides highly specific molecular information that avoids the bioinformatic challenge of protein inference. However, the technique has been difficult to implement widely because of inherent limitations of existing sample preparation methods and instrumentation. Recent improvements in proteoform pre-fractionation and the availability of high-resolution benchtop mass spectrometers have made it possible to use high-throughput TDP for the analysis of complex clinical samples. Here, we provide a comprehensive protocol for analysis of a common sample type in translational research: human peripheral blood mononuclear cells (PBMCs). The pipeline comprises multiple workflows that can be treated as modular by the reader and used for various applications. First, sample collection and cell preservation are described for two clinical biorepository storage schemes. Cell lysis and proteoform pre-fractionation by gel-eluted liquid fractionation entrapment electrophoresis are then described. Importantly, instrument setup and liquid chromatography-tandem MS are described for TDP analyses, which rely on high-resolution Fourier-transform MS. Finally, data processing and analysis are described using two different, application-dependent software tools: ProSight Lite for targeted analyses of one or a few proteoforms and TDPortal for high-throughput TDP in discovery mode. For a single sample, the minimum completion time of the entire experiment is 72 h.
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