ArticleMolecular & cellular proteomics : MCP2019
Accurate Estimation of Context-Dependent False Discovery Rates in Top-Down Proteomics.
Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Properties, Origin, and Consistency of Truncated Proteoforms Across Top-Down Proteomic Studies.Molecular & cellular proteomics : MCP · 2025Pooled it
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- SPAP: Soluble Human Plasma Proteoform Analysis via Acetonitrile Precipitation and Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2026Article
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- Proteoform-predictor: Increasing the Phylogenetic Reach of Top-Down Proteomics.Journal of proteome research · 2025Article
- Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression.Molecular & cellular proteomics : MCP · 2024Article
- Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.Journal of proteome research · 2024Article
- Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression.bioRxiv : the preprint server for biology · 2024Article
- Orbitrap Mass Spectrometry and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Enable the in-Depth Analysis of Human Serum Proteoforms.Journal of proteome research · 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
- 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
- FLASHIda enables intelligent data acquisition for top-down proteomics to boost proteoform identification counts.Nature communications · 2022Article
- Mapping the Proteoform Landscape of Five Human Tissues.Journal of proteome research · 2022Article
- The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells.Science (New York, N.Y.) · 2022Article
- Reassembling protein complexes after controlled disassembly by top-down mass spectrometry in native mode.International journal of mass spectrometry · 2021Article
- Increased Single-Spectrum Top-Down Protein Sequence Coverage in Trapping Mass Spectrometers with Chimeric Ion Loading.Analytical chemistry · 2020Article
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Abstract
Within the last several years, top-down proteomics has emerged as a high throughput technique for protein and proteoform identification. This technique has the potential to identify and characterize thousands of proteoforms within a single study, but the absence of accurate false discovery rate (FDR) estimation could hinder the adoption and consistency of top-down proteomics in the future. In automated identification and characterization of proteoforms, FDR calculation strongly depends on the context of the search. The context includes MS data quality, the database being interrogated, the search engine, and the parameters of the search. Particular to top-down proteomics-there are four molecular levels of study: proteoform spectral match (PrSM), protein, isoform, and proteoform. Here, a context-dependent framework for calculating an accurate FDR at each level was designed, implemented, and validated against a manually curated training set with 546 confirmed proteoforms. We examined several search contexts and found that an FDR calculated at the PrSM level under-reported the true FDR at the protein level by an average of 24-fold. We present a new open-source tool, the TDCD_FDR_Calculator, which provides a scalable, context-dependent FDR calculation that can be applied post-search to enhance the quality of results in top-down proteomics from any search engine.
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