Enhanced information output from shotgun proteomics data by protein quantification and peptide quality control (PQPQ)
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We present a tool to improve quantitative accuracy and precision in mass spectrometry based on shotgun proteomics: protein quantification by peptide quality control, PQPQ. The method is based on the assumption that the quantitative pattern of peptides derived from one protein will correlate over several samples. Dissonant patterns arise either from outlier peptides or because of the presence of different protein species. By correlation analysis, protein quantification by peptide quality control identifies and excludes outliers and detects the existence of different protein species. Alternative protein species are then quantified separately. By validating the algorithm on seven data sets related to different cancer studies we show that data processing by protein quantification by peptide quality control improves the information output from shotgun proteomics. Data from two labeling procedures and three different instrumental platforms was included in the evaluation. With this unique method using both peptide sequence data and quantitative data we can improve the quantitative accuracy and precision on the protein level and detect different protein species.
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Additional sources of uncertainty may arise from processes such as protein quantification in bottom-up proteomics because measurements are made at the peptide level and isoforms can be difficult to identify.
“additional sources of uncertainty may arise from processes such as protein quantification in bottom-up proteomics (Rifai et al., 2006; Plubell et al., 2022) as measurements are made at the peptide level and isoforms can be difficult to identify (Forshed et al., 2011; Webb-Robertson et al., 2014).”
From Missing data in multi-omics integration: Recent advances through artificial intelligence (2023) · cites this paper as Forshed et al., 2011
Several proposed methods exclude peptide measurements from the aggregate protein quantity when they are outliers relative to other peptides mapping to the same protein-coding gene.
“The approach of several proposed methods focuses on the exclusion of peptide measurements from inclusion in the aggregate protein quantity if they are outliers from other peptide measurements mapping to the same protein coding gene.(28–33)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [28]
Outlier-exclusion methods improve protein concentration estimates but still report only one protein quantity and ignore peptides that do not agree with that value.
“While these all demonstrate improved protein concentration estimates, they still only report a single protein quantity and ignore peptides that do not agree with that single value.”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [28]
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- Authors
- Forshed, J., Johansson, H. J., Pernemalm, M., Branca, R. M. M., Sandberg, A., & Lehtiö, J.
- Affiliations
- Science for Life Laboratory (SE)
- Corresponding author
- Forshed, Jenny
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 10
- Issue
- 10
- Pages
- M111.010264
- ISSN
- 1535-9476 (ISSN-L)
- PMC
- PMC3205873
- OpenAlex
- W2137941815
- Cited by
- 32
- References
- 35
- Citations by year
- 2025: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular & Cellular Proteomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agilent Foundation
- Cancerfonden
- Stockholms Läns Landsting
- Vetenskapsrådet
- Cancerföreningen i Stockholm
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
- Keywords
- protein quantification, shotgun proteomics, protein isoforms, isobaric labeling, cancer proteomics
- MeSH terms
- Algorithms, Chromatography, Liquid, Humans, Isotope Labeling, Peptides, Proteins, Quality Control, Software, Mass Spectrometry, Statistics as Topic, Alternative Splicing, Sequence Analysis, Protein, Databases, Protein, Proteomics, Tandem Mass Spectrometry
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