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

Yuliya Karpievitch, Jeff Stanley, Thomas Taverner, Jianhua Huang, Joshua N. Adkins, Charles Ansong, Fred Heffron, Thomas O. Metz, Wei Jun Qian, Hyunjin Yoon, Richard D. Smith, Alan R. Dabney

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97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2028-2034
Number of pages7
JournalBioinformatics
Volume25
Issue number16
DOIs
Publication statusPublished - 1 Aug 2009
Externally publishedYes

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Karpievitch, Y., Stanley, J., Taverner, T., Huang, J., Adkins, J. N., Ansong, C., ... Dabney, A. R. (2009). A statistical framework for protein quantitation in bottom-up MS-based proteomics. Bioinformatics, 25(16), 2028-2034. https://doi.org/10.1093/bioinformatics/btp362