Issues of processing and multiple testing of SELDI-TOF MS proteomic data

Stat Appl Genet Mol Biol. 2006:5:Article11. doi: 10.2202/1544-6115.1198. Epub 2006 Apr 21.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Algorithms
  • Bone Marrow Cells / metabolism
  • Child
  • Data Interpretation, Statistical
  • Humans
  • Leukemia, Myeloid / metabolism*
  • Neoplasm Proteins / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Probability
  • Proteomics / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

  • Neoplasm Proteins