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QA/QC of SELDI Data in Clinical Studies

QA/QC of SELDI Data in Clinical Studies. 6-8-2006 CAMDA. Simon Lin Northwestern University. CDC Toni Whistler Suzanne Vernon Northwestern Pan Du Warren Kibbe Simon Lin. Duke Radiology Ned Patz Mike Campa Duke Bioinformatics Patrick McConnell Rich Haney Sal Mungal.

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QA/QC of SELDI Data in Clinical Studies

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  1. QA/QC of SELDI Data in Clinical Studies 6-8-2006 CAMDA Simon Lin Northwestern University

  2. CDC Toni Whistler Suzanne Vernon Northwestern Pan Du Warren Kibbe Simon Lin Duke Radiology Ned Patz Mike Campa Duke Bioinformatics Patrick McConnell Rich Haney Sal Mungal Acknowledgements

  3. Agenda • Challenges in clinical proteomics • Hypothesis: QA/QC is the key • Potential biomarkers of CFS • Future: Online QC

  4. “The standard procedure of using SELDI-TOF mass spectra to construct a classifier is ________ . ” - Dr. Brian Luke, NCI “The proper construction of SELDI-TOF-based classifiers for early disease detection”, CHI Proteomics Conference Brochure, 2006 WRONG

  5. TEMPERAMENTAL “Mass spectrometers can be __________. ” - Coombes et. al., Nature Biotechnology, 3: 291-292, 2005

  6. Evidences (I) Gusev et. al., Analytical Chemistry 67: 1034, 1995

  7. Evidences (II) - Image from Invitrogen.co.jp

  8. Evidences (III) • Same biological sample • Technical Replicates • m/z: 5.0K to 8.5K • CAMDA’06 QC serum

  9. Hypothesis Removing spectra of poor quality will improve our capability to detect biomarkers.

  10. How to measure quality • Classification confidence • Correlation coefficient: r2 • Principal component analysis • Signal-to-noise Ratio (SNR) • After-the-fact: QA • On-the-spot: QC

  11. Why Wavelet • Can be directly applied to raw data • Mutliscale analysis • Noise • Signal • Baseline

  12. Wavelets • A data projection method • From raw data space to wavelet space • c.f. Fourier transform • A multi-resolution analysis method • Finer v.s. coarse scale

  13. Estimating SNR • Global method • Partition the measurements into noise, signal, and baseline • Local method • For each peak, estimate the SNR Raw data Signal Noise

  14. Raw spectrum QA step DWT-based SNR estimation Baseline removal and normalization Spectrum alignment CWT-based peak detection Classification and other data analysis Biomarker identification by statistical tests

  15. Improved biomarker detection QA cutoff: SNR > 5

  16. Advantages of SNR • Complementary to outlier-resistant statistics • Online QC • Simple • Can be done in real time

  17. Conclusions “Mass spectrometers can be __________. ” ONLINEQUALITY CONTROL - Coombes et. al., Nature Biotechnology, 3: 291-292, 2005 TEMPERAMENTAL “_________ nature of conclusions of most serum proteomics studies.” PROVISIONAL

  18. Ben Bolstad, PLM Image Hall of Fame http://plmimagegallery.bmbolstad.com

  19. Must read papers • The Ovarian cancer controversy • Wavelet smoothing

  20. Proteomics Challenges Hilario et al., Mass Spectrometry Reviews, 25: 409-449, 2006

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