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A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors.


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.

SUBMITTER: Webb-Robertson BJ 

PROVIDER: S-EPMC3517140 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors.

Webb-Robertson Bobbie-Jo M BJ   Matzke Melissa M MM   Jacobs Jon M JM   Pounds Joel G JG   Waters Katrina M KM  

Proteomics 20111117 24


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  ...[more]

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