ArticleMolecular & cellular proteomics : MCP2009
Sensitive and specific identification of wild type and variant proteins from 8 to 669 kDa using top-down mass spectrometry.
Article in Molecular & cellular proteomics : MCP, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- An Overview of Mass Spectrometry-Based Methods to Analyze Post-Translational Modifications.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- ResNeXt-Based Rescoring Model for Proteoform Characterization in Top-Down Mass Spectra.Interdisciplinary sciences, computational life sciences · 2025Article
- Top-Down Protein Analysis by Tandem-Trapped Ion Mobility Spectrometry/Mass Spectrometry (Tandem-TIMS/MS) Coupled with Ultraviolet Photodissociation (UVPD) and Parallel Accumulation/Serial Fragmentation (PASEF) MS/MS Analysis.Journal of the American Society for Mass Spectrometry · 2023Article
- Identification of Splice Variants and Isoforms in Transcriptomics and Proteomics.Annual review of biomedical data science · 2023Review
- Comparing Top-Down Proteoform Identification: Deconvolution, PrSM Overlap, and PTM Detection.Journal of proteome research · 2023Article
- Internal Fragment Ions Disambiguate and Increase Identifications in Top-Down Proteomics.Journal of proteome research · 2021Article
- Novel Strategies to Address the Challenges in Top-Down Proteomics.Journal of the American Society for Mass Spectrometry · 2021Review
- Top-down proteomics: challenges, innovations, and applications in basic and clinical research.Expert review of proteomics · 2020Article
- Constructing Human Proteoform Families Using Intact-Mass and Top-Down Proteomics with a Multi-Protease Global Post-Translational Modification Discovery Database.Journal of proteome research · 2019Article
- Top-Down Proteomics of Medicinal Cannabis.Proteomes · 2019Article
- Top-down mass spectrometry of intact phosphorylated β-casein: Correlation between the precursor charge state and internal fragments.Journal of mass spectrometry : JMS · 2019Article
- Accurate Estimation of Context-Dependent False Discovery Rates in Top-Down Proteomics.Molecular & cellular proteomics : MCP · 2019Article
- A Markov Chain Monte Carlo Method for Estimating the Statistical Significance of Proteoform Identifications by Top-Down Mass Spectrometry.Journal of proteome research · 2019Article
- Identification and Quantification of Murine Mitochondrial Proteoforms Using an Integrated Top-Down and Intact-Mass Strategy.Journal of proteome research · 2018Article
- A graph-based filtering method for top-down mass spectral identification.BMC genomics · 2018Article
- Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications.Proteomics · 2018Review
- Systematic Evaluation of Protein Sequence Filtering Algorithms for Proteoform Identification Using Top-Down Mass Spectrometry.Proteomics · 2018Article
- An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes.Nature chemistry · 2018Article
- Expanding Proteoform Identifications in Top-Down Proteomic Analyses by Constructing Proteoform Families.Analytical chemistry · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
Top-down and bottom-up mass spectrometry methods can generate gas phase fragments and use these to identify proteins. Top-down methods, in addition, can provide the mass of the protein itself and therefore additional structural information. Despite the conceptual advantage of top-down methods, the market share advantage belongs to bottom-up methods as a result of their more robust sample preparation, fragmentation, and data processing methods. Here we report improved fragmentation and data processing methods for top-down mass spectrometry. Specifically we report the use of funnel-skimmer dissociation, a variation of nozzle-skimmer dissociation, and compare its performance with electron capture dissociation. We also debut BIG Mascot, an extended version of Mascot with incorporated top-down MS(2) search ability and the first search engine that can perform both bottom-up and top-down searches. Using BIG Mascot, we demonstrated the ability to identify proteins 1) using only intact protein MS(1), 2) using only MS(2), and 3) using the combination of MS(1) and MS(2). We correctly identified proteins with a wide range of masses, including 13 amyotrophic lateral sclerosis-associated variants of the protein Cu/Zn-superoxide dismutase, and extended the upper mass limit of top-down protein identification to 669 kDa by identifying thyroglobulin.
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