ArticleJournal of proteome research2020
Improving Proteoform Identifications in Complex Systems Through Integration of Bottom-Up and Top-Down Data.
Article in Journal of proteome research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The "2DE-Pattern" Database for Inventory of Proteoform Profiles: 2026 Upgrade and Update on Outcomes.Proteomes · 2026Article
- Advances in Mass Spectrometry Instrumentation and Methodology for Analysis of Alternative Protein Isoforms.Journal of mass spectrometry : JMS · 2026Review
- Article
- Puzzle of Proteoform Variety-Where Is a Key?Proteomes · 2024Article
- Spectral averaging with outlier rejection algorithms to increase identifications in top-down proteomics.Proteomics · 2024Article
- How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?Proteomes · 2024Article
- Chronic Pelvic Pain, Vulvar Pain Disorders, and Proteomics Profiles: New Discoveries, New Hopes.Biomedicines · 2023Review
- Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology.Cells · 2023Review
- Characterization of Proteoform Post-Translational Modifications by Top-Down and Bottom-Up Mass Spectrometry in Conjunction with Annotations.Journal of proteome research · 2023Article
- Recent advances (2019-2021) of capillary electrophoresis-mass spectrometry for multilevel proteomics.Mass spectrometry reviews · 2023Review
- Proteoforms expand the world of microproteins and short open reading frame-encoded peptides.iScience · 2023Review
- Spatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform.Molecular & cellular proteomics : MCP · 2023Article
- Integrated top-down and bottom-up proteomics mass spectrometry for the characterization of endogenous ribosomal protein heterogeneity.Journal of pharmaceutical analysis · 2023Article
- Review
- Identification of Inflammatory Proteomics Networks of Toll-like Receptor 4 through Immunoprecipitation-Based Chemical Cross-Linking Proteomics.Proteomes · 2022Article
- Putting Humpty Dumpty Back Together Again: What Does Protein Quantification Mean in Bottom-Up Proteomics?Journal of proteome research · 2022Article
- Proteomics Standards Initiative's ProForma 2.0: Unifying the Encoding of Proteoforms and Peptidoforms.Journal of proteome research · 2022Article
- Automated Assignment of Proteoform Classification Levels.Journal of proteome research · 2021Article
- Quantitative proteomics characterization of cancer biomarkers and treatment.Molecular therapy oncolytics · 2021Review
- Profiling Dopamine-Induced Oxidized Proteoforms of β-synuclein by Top-Down Mass Spectrometry.Antioxidants (Basel, Switzerland) · 2021Article
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Authors and funding
5 authors.
Funding
Abstract
Cellular functions are performed by a vast and diverse set of proteoforms. Proteoforms are the specific forms of proteins produced as a result of genetic variations, RNA splicing, and post-translational modifications (PTMs). Top-down mass spectrometric analysis of intact proteins enables proteoform identification, including proteoforms derived from sequence cleavage events or harboring multiple PTMs. In contrast, bottom-up proteomics identifies peptides, which necessitates protein inference and does not yield proteoform identifications. We seek here to exploit the synergies between these two data types to improve the quality and depth of the overall proteomic analysis. To this end, we automated the large-scale integration of results from multiprotease bottom-up and top-down analyses in the software program Proteoform Suite and applied it to the analysis of proteoforms from the human Jurkat T lymphocyte cell line. We implemented the recently developed proteoform-level classification scheme for top-down tandem mass spectrometry (MS/MS) identifications in Proteoform Suite, which enables users to observe the level and type of ambiguity for each proteoform identification, including which of the ambiguous proteoform identifications are supported by bottom-up-level evidence. We used Proteoform Suite to find instances where top-down identifications aid in protein inference from bottom-up analysis and conversely where bottom-up peptide identifications aid in proteoform PTM localization. We also show the use of bottom-up data to infer proteoform candidates potentially present in the sample, allowing confirmation of such proteoform candidates by intact-mass analysis of MS1 spectra. The implementation of these capabilities in the freely available software program Proteoform Suite enables users to integrate large-scale top-down and bottom-up data sets and to utilize the synergies between them to improve and extend the proteomic analysis.
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