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Journal of Computational Biology
Bayesian Estimation of Transcript Levels Using a General Model of Array Measurement Noise

To cite this article:
Ron O. Dror, Jonathan G. Murnick, Nicola J. Rinaldi, Voichita D. Marinescu, Ryan M. Rifkin, Richard A. Young. Journal of Computational Biology. June 2003, 10(3-4): 433-452. doi:10.1089/10665270360688110.

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Ron O. Dror
Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139
Jonathan G. Murnick
Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139
Nicola J. Rinaldi
Department of Biology, MIT, Cambridge, MA 02139, and Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142
Voichita D. Marinescu
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139
Ryan M. Rifkin
Department of Operations Research and Center For Biological and Computational Learning, MIT, Cambridge, MA 02139
Richard A. Young
Department of Biology, MIT, Cambridge, MA 02139, and Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142

Gene arrays demonstrate a promising ability to characterize expression levels across the entire genome but suffer from significant levels of measurement noise. We present a rigorous new approach to estimate transcript levels and ratios from one or more gene array experiments, given a model of measurement noise and available prior information. The Bayesian estimation of array measurements (BEAM) technique provides a principled method to identify changes in expression level, combine repeated measurements, or deal with negative expression level measurements. BEAM is more flexible than existing techniques, because it does not assume a specific functional form for noise and prior models. Instead, it relies on computational techniques that apply to a broad range of models. We use Affymetrix yeast chip data to illustrate the process of developing accurate noise and prior models from existing experimental data. The resulting noise model includes novel features such as heavy-tailed additive noise and a gene-specific bias term. We also verify that the resulting noise and prior models fit data from an Affymetrix human chip set.

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