MixThres : mixture models to define a hybridization threshold in DNA microarray experiments

Even if one of the major applications of two-color DNA microarray hybridizations is to detect differentially expressed genes using intensity log-ratios, single channel signals provide also useful information as absolute value measurements which allow the description of gene expression patterns. In this context, it becomes crucial to determine the set of probes that hybridize, that is for which the intensity signal is greater than a hybridization threshold to be fixed. Existing procedures are either an arbitrary thresholding or require the knowledge of a population of non-hybridized probes. In this work we present the MixThres method to determine an adaptive hybridization threshold from intensity levels of the complete set of probes hybridized on a chip. We define a hybridization threshold based on the histogram of the probe intensity values. Our procedure is divided into two steps. First the intensity distribution is estimated using mixture models. Second a hybridization threshold is defined from the components of the mixture. We validate our method on DNA tiling array and expression array data. We show that our method has a good reproducibility, its specificity is greater than 97 % and its precision of 88 %. The R package MixThres is available at http://www.agroparistech.fr/mia/outil.html