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General statistical framework for quantitative proteomics by stable isotope labeling

AutorNavarro, Pedro J.; Trevisan-Herraz, Marco; Bonzón-Kulichenko, Elena ; Núñez, Estefanía; Martínez-Acedo, Pablo ; Pérez-Hernández, Daniel; Jorge, Inmaculada; Mesa, Raquel ; Carrascal, Montserrat ; Vázquez, Jesús
Palabras claveQuantitative proteomics
stable isotope labeling
statistical analysis
yeast
Fecha de publicación31-ene-2014
EditorAmerican Chemical Society
CitaciónJournal of Proteome Research 13(3): 1234-1247 (2014)
ResumenThe combination of stable isotope labeling (SIL) with mass spectrometry (MS) allows comparison of the abundance of thousands of proteins in complex mixtures. However, interpretation of the large data sets generated by these techniques remains a challenge because appropriate statistical standards are lacking. Here, we present a generally applicable model that accurately explains the behavior of data obtained using current SIL approaches, including 18O, iTRAQ, and SILAC labeling, and different MS instruments. The model decomposes the total technical variance into the spectral, peptide, and protein variance components, and its general validity was demonstrated by confronting 48 experimental distributions against 18 different null hypotheses. In addition to its general applicability, the performance of the algorithm was at least similar than that of other existing methods. The model also provides a general framework to integrate quantitative and error information fully, allowing a comparative analysis of the results obtained from different SIL experiments. The model was applied to the global analysis of protein alterations induced by low H2O2 concentrations in yeast, demonstrating the increased statistical power that may be achieved by rigorous data integration. Our results highlight the importance of establishing an adequate and validated statistical framework for the analysis of high-throughput data. © 2014 American Chemical Society.
DescripciónPedro J. Navarro et al.
Versión del editorhttp://dx.doi.org/10.1021/pr4006958
URIhttp://hdl.handle.net/10261/124921
DOI10.1021/pr4006958
Identificadoresdoi: 10.1021/pr4006958
issn: 1535-3893
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