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Comparative Study
. 2016 Apr 1;15(4):1116-25.
doi: 10.1021/acs.jproteome.5b00981. Epub 2016 Mar 1.

Accounting for the Multiple Natures of Missing Values in Label-Free Quantitative Proteomics Data Sets to Compare Imputation Strategies

Cosmin Lazar  1   2   3 , Laurent Gatto  4   5 , Myriam Ferro  1   2   3 , Christophe Bruley  1   2   3 , Thomas Burger  1   6   2   3
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Free article
Comparative Study

Accounting for the Multiple Natures of Missing Values in Label-Free Quantitative Proteomics Data Sets to Compare Imputation Strategies

Cosmin Lazar et al. J Proteome Res. .
Free article

Abstract

Missing values are a genuine issue in label-free quantitative proteomics. Recent works have surveyed the different statistical methods to conduct imputation and have compared them on real or simulated data sets and recommended a list of missing value imputation methods for proteomics application. Although insightful, these comparisons do not account for two important facts: (i) depending on the proteomics data set, the missingness mechanism may be of different natures and (ii) each imputation method is devoted to a specific type of missingness mechanism. As a result, we believe that the question at stake is not to find the most accurate imputation method in general but instead the most appropriate one. We describe a series of comparisons that support our views: For instance, we show that a supposedly "under-performing" method (i.e., giving baseline average results), if applied at the "appropriate" time in the data-processing pipeline (before or after peptide aggregation) on a data set with the "appropriate" nature of missing values, can outperform a blindly applied, supposedly "better-performing" method (i.e., the reference method from the state-of-the-art). This leads us to formulate few practical guidelines regarding the choice and the application of an imputation method in a proteomics context.

Keywords: label-free relative quantitative proteomics; missing value imputation.

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