Bioinformatics Advance Access published online on January 29, 2004
Bioinformatics, doi:10.1093/bioinformatics/btg484
Bioinformatics © Oxford University Press 2004; all rights reserved
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1 Department of Biostatistics U.T. M.D. Anderson Cancer Center 1515 Holcombe Blvd, Box 447 Houston, TX 77030-4009, USA
* To whom correspondence should be addressed. E-mail: kabagg{at}mdanderson.org.
Motivation: There has been much interest in using patterns derived from surface-enhanced laser desorption and ionization (SELDI) protein mass spectra from serum to differentiate samples from patients both with and without disease. Such patterns have been used without identification of the underlying proteins responsible. However, there are questions as to the stability of this procedure over multiple experiments. Results: We compared SELDI proteomic spectra from serum from 3 experiments by the same group (Petricoin et al., 2002) on separating ovarian cancer from normal tissue. These spectra are available on the web at http://clinicalproteomics.steem.com. In general, the results were not reproducible across experiments. Baseline correction prevents reproduction of the results for two of the experiments. In one experiment there is evidence of a major shift in protocol mid-experiment which could bias the results. In another, structure in the noise regions of the spectra allows us to distinguish normal from cancer, suggesting that the normals and cancers were processed differently. Sets of features found to discriminate well in one experiment do not generalize to other experiments. Finally, the mass calibration in all three experiments appears suspect. Taken together, these and other concerns suggest that much of the structure uncovered in these experiments could be due to artifacts of sample processing, not to the underlying biology of cancer. We provide some guidelines for design and analysis in experiments like these to better ensure reproducible, biologically meaningfully results. Availability: The MATLAB and Perl code used in our analyses is available at bioinformatics.mdanderson.org.
Revised October 14, 2003
Accepted October 16, 2003
Article
Reproducibility of SELDI-TOF protein patterns in serum: comparing data sets from different experiments
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