A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors |
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Authors: | Webb-Robertson Bobbie-Jo M Matzke Melissa M Jacobs Jon M Pounds Joel G Waters Katrina M |
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Affiliation: | Pacific Northwest National Laboratory, USA. bj@pnl.gov |
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Abstract: | Quantification of LC-MS peak intensities assigned during peptide identification in a typical comparative proteomics experiment will deviate from run-to-run of the instrument due to both technical and biological variation. Thus, normalization of peak intensities across an LC-MS proteomics dataset is a fundamental step in pre-processing. However, the downstream analysis of LC-MS proteomics data can be dramatically affected by the normalization method selected. Current normalization procedures for LC-MS proteomics data are presented in the context of normalization values derived from subsets of the full collection of identified peptides. The distribution of these normalization values is unknown a priori. If they are not independent from the biological factors associated with the experiment the normalization process can introduce bias into the data, possibly affecting downstream statistical biomarker discovery. We present a novel approach to evaluate normalization strategies, which includes the peptide selection component associated with the derivation of normalization values. Our approach evaluates the effect of normalization on the between-group variance structure in order to identify the most appropriate normalization methods that improve the structure of the data without introducing bias into the normalized peak intensities. |
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Keywords: | Bias Bioinformatics Normalization Peptide filtering Shotgun proteomics Statistical models |
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