Bioinformatics Advance Access originally published online on March 27, 2006
Bioinformatics 2006 22(12):1515-1523; doi:10.1093/bioinformatics/btl106
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Finding regions of significance in SELDI measurements for identifying protein biomarkers
1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Stockholm, Sweden
2 Cancer Centrum Karolinska, Karolinska Institutet Stockholm, Sweden
3 Center for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore and Genome Institute of Singapore Singapore
4 Clinical Proteomics, Karolinska Biomics Center, Karolinska University Hospital Stockholm, Sweden
*To whom correspondence should be addressed.
Motivation: There is a well-recognized potential of protein expression profiling using the surface-enhanced laser desorption and ionization technology for discovering biomarkers that can be applied in clinical diagnosis, prognosis and therapy prediction. The pre-processing of the raw data, however, is still problematic.
Methods: We focus on the peak detection step, where the standard method is marked by poor specificity. Currently, scientists need to inspect individual spectra visually and laboriously in order to verify that spectral peaks identified by the standard method are real. Motivated by this multi-spectral process, we investigate an analytical approach—called RS for ‘regions of significance’—that reduces the data to a single spectrum of F-statistics capturing significant variability between spectra. To account for multiple testing, we use a false discovery rate criterion for identifying potentially interesting proteins.
Results: We show that RS has better operating characteristics than several existing methods and demonstrate routine applications on a number of large datasets.
Availability: RS is implemented in an R package called ProSpect which is available at http://www.meb.ki.se/~yudpaw
Contact: yudi.pawitan{at}ki.se
Supplementary information: Supplementary data are available at Bioinformatics online.
Received on January 31, 2005; revised on March 7, 2006; accepted on March 18, 2006
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