Issues of Processing and Multiple Testing of SELDI-TOF MS Proteomic Data.

Autor: Birkner, Merrill D., Hubbard, Alan E., Van der Laan, Mark J., Skibola, Christine F., Hegedus, Christine M., Smith, Martyn T.
Předmět:
Zdroj: Statistical Applications in Genetics & Molecular Biology; 2006, Vol. 5 Issue 1, p1-24, 24p
Abstrakt: A new data filtering method for SELDI-TOF MS proteomic spectra data is described. We examined technical repeats (2 per subject) of intensity versus m/z (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As others have noted, the type of data processing as well as experimental variability can have a disproportionate impact on the list of "interesting" proteins (see Baggerly et al. (2004)). We propose a list of processing and multiple testing techniques to correct for 1) background drift; 2) filtering using smooth regression and cross-validated bandwidth selection; 3) peak finding; and 4) methods to correct for multiple testing (van der Laan et al. (2005)). The result is a list of proteins (indexed by m/z) where average expression is significantly different among disease (or treatment, etc.) groups. The procedures are intended to provide a sensible and statistically driven algorithm, which we argue provides a list of proteins that have a significant difference in expression. Given no sources of unmeasured bias (such as confounding of experimental conditions with disease status), proteins found to be statistically significant using this technique have a low probability of being false positives. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index