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Bioinformatics Advance Access published online on July 29, 2004
Bioinformatics, doi:10.1093/bioinformatics/bth446
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received July 17, 2004
Revised June 18, 2004
Accepted July 26, 2004

Article

Quantifying reproducibility for differential proteomics: noise analysis for protein liquid chromatography-mass spectrometry of human serum

Markus Anderle 1*, Sushmita Roy 1, Hua Lin 1, Christopher Becker 1, Keith Joho 1

1 SurroMed, Inc., 1430 O'Brien Drive, Menlo Park, CA 94025, USA

* To whom correspondence should be addressed. E-mail: manderle{at}surromed.com.


  Abstract

Using replicated human serum samples, we applied an error model for proteomic differential expression profiling for a high resolution liquid chromatography-mass spectrometry (LC-MS) platform. The detailed noise analysis presented here uses an experimental design that separates variance caused by sample preparation from variance due to analytical equipment. An analytic approach based on a two-component error model was applied, and in combination with an existing data driven technique that utilizes local sample averaging, we characterized and quantified the noise variance as a function of mean peak intensity. The results indicate that for processed LC-MS data a constant coefficient of variation is dominant for high intensities, whereas a model for low intensities explains Poisson-like variations. This result leads to a quadratic variance model which is used for the estimation of sample preparation noise present in LC-MS data.


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