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Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments
Keith A Baggerly1, Jeffrey S Morris, Kevin R Coombes
1Department of Biostatistics, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 447, Houston, TX 77030-4009, USA. kabagg@mdanderson.org
Bioinformatics (Oxford, England)
|January 31, 2004
Summary
Reproducibility issues plague surface-enhanced laser desorption and ionization (SELDI) protein mass spectrometry for disease biomarker discovery. Results suggest artifacts, not biology, drive observed patterns, impacting cancer diagnostics.
Area of Science:
- Biochemistry
- Proteomics
- Biomarker Discovery
Background:
- Surface-enhanced laser desorption and ionization (SELDI) protein mass spectra show promise for disease detection.
- Identifying disease-specific protein patterns from serum is of significant interest.
- Concerns exist regarding the reproducibility of SELDI-based diagnostic procedures.
Purpose of the Study:
- To evaluate the reproducibility of SELDI proteomic spectra across multiple experiments for ovarian cancer detection.
- To identify potential sources of variability and artifacts in SELDI serum analysis.
- To provide guidelines for improving the reliability of SELDI-based biomarker studies.
Main Methods:
- Comparison of SELDI proteomic spectra from three independent serum experiments.
- Analysis of spectral data for reproducibility and potential artifacts.
- Evaluation of baseline correction and mass calibration methods.
Main Results:
- Significant irreproducibility of SELDI spectra was observed across the three experiments.
- Baseline correction failed to ensure consistent results in two experiments.
- Potential protocol shifts and processing differences between sample groups were identified.
- Feature sets effective in one experiment did not generalize to others.
- Suspect mass calibration across all experiments raises concerns.
Conclusions:
- Observed patterns in SELDI serum spectra may result from experimental artifacts rather than true biological differences.
- The reliability of SELDI for distinguishing cancer from normal tissue in these experiments is questionable.
- Recommendations are provided for designing more robust and reproducible SELDI proteomic studies.