Improving background correction for Illumina BeadArrays: the normal-gamma model

Statistics – Applications

Scientific paper

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Scientific paper

Motivation: Illumina beadarray technology provides high quality data, including non specific negative control features which allow a precise estimation of the background noise. As reported in many studies, the traditional background subtraction proposed in BeadStudio leads to an important loss of information by generating negative values. A background correction method modeling the observed intensities as sum of exponentially distributed signal and normally distributed noise has been developed to address this issue. Even though it is widely used, this parametric model does not fit Illumina genome-wide expression array. Hence background corrections derived from this model may lead to wrong estimation. Results: A new modeling that preserves positivity and properly fits Illumina genome-wide arrays is proposed in order to improve background correction, and the associated background correction is developed. Our model based on a gamma distributed signal and a normal distributed noise proves to be more accurate. It is shown on two types of Illumina genome-wide expression data that this model offers a more correct fit of the observed intensities. Moreover on simulated data, the associated background correction proves to perform better than existing methods based on the normal-exponential model and shows robustness with respect to departures from normally distributed noise. Availability: The R-code to perform the background correction in this new model are available in the R package NormalGamma.

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