Cited by 179Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsBioinformatics and Genomic Networks

A statistical framework for protein quantitation in bottom-up MS-based proteomics

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Karpievitch, Yuliya, Stanley, Jeff, Taverner, Thomas, Huang, Jianhua, Adkins, Joshua N., Ansong, Charles, Heffron, Fred, Metz, Thomas O. +4 more·2009·Bioinformatics

Abstract

MOTIVATION: Quantitative mass spectrometry-based proteomics requires protein-level estimates and associated confidence measures. Challenges include the presence of low quality or incorrectly identified peptides and informative missingness. Furthermore, models are required for rolling peptide-level information up to the protein level. RESULTS: We present a statistical model that carefully accounts for informative missingness in peak intensities and allows unbiased, model-based, protein-level estimation and inference. The model is applicable to both label-based and label-free quantitation experiments. We also provide automated, model-based, algorithms for filtering of proteins and peptides as well as imputation of missing values. Two LC/MS datasets are used to illustrate the methods. In simulation studies, our methods are shown to achieve substantially more discoveries than standard alternatives. AVAILABILITY: The software has been made available in the open-source proteomics platform DAnTE (http://omics.pnl.gov/software/).

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  • Peptides may be missing from one or more samples due to a variety of underlying mechanisms, which can result in non-trivial amounts of potential observations being missing.

    “Peptides may be missing from one or more samples due to a variety of underlying mechanisms (Daly et al., 2008; Karpievitch et al., 2009), which can result in non-trivial amounts of potential observations being missing.”

    From Missing data in multi-omics integration: Recent advances through artificial intelligence (2023) · cites this paper as Karpievitch et al., 2009

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Authors
Karpievitch, Y., Stanley, J., Taverner, T., Huang, J., Adkins, J. N., Ansong, C., Heffron, F., Metz, T. O., Qian, W.-J., Yoon, H., Smith, R. D., & Dabney, A. R.
Affiliations
  • Pacific Northwest National Laboratory (US)
  • 1 Department of Statistics, Texas A&M University, 3143 TAMU, College Station, TX 77843, 2Pacific Northwest National Laboratory, P.O. Box 999, Richland, WA 99352 and 3Molecular Microbiology and Immunology, Oregon Health and Science University, Mail Code L220, Portland, OR 97201, USA
Corresponding author
Dabney, Alan R.
Venue
Bioinformatics
Published
2009-06-17
Volume
25
Issue
16
Pages
2028-2034
ISSN
  • 1367-4803 (ISSN-L)
  • 1367-4811
OpenAlex
W2125419939
Cited by
176
References
29
Citations by year
2026: 5 · 2025: 2 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 11 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 14 · 2014: 20 · 2013: 12 · 2012: 19
FWCI
5.30
Type
journal article
Language
en
Open access
Locations
  • Bioinformatics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eCite Digital Repository (University of Tasmania) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (DK070146)
  • National Cancer Institute (R25 CA90301, R25CA090301)
  • National Institute of Allergy and Infectious Diseases (Y1 AI 489401, R01AI022933)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK070146, R21DK070146, R33DK070146)
  • Pacific Northwest National Laboratory
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 › Bioinformatics and Genomic Networks
Keywords
protein quantification, shotgun proteomics, label-free quantification, informative missingness, Dante
MeSH terms
Proteins, Mass Spectrometry, Models, Statistical, Proteome, Databases, Protein, Proteomics

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