Estimating gene signals from noisy microarray images

Abstract—In oligonucleotide microarray experiments, noise is a challenging problem, as biologists now are studying their organisms not in isolation but in the context of a natural en-vironment. In low photomultiplier tube (PMT) voltage images, weak gene signals and their interactions with the background fluorescence noise are most problematic. In addition, nonspecific sequences bind to array spots intermittently causing inaccurate measurements. Conventional techniques cannot precisely separate the foreground and the background signals. In this paper, we pro-pose analytically based estimation technique. We assume a priori spot-shape information using a circular outer periphery with an elliptical center hole. We assume Gaussian statistics for modeling both the foreground and background signals. The mean of the foreground signal quantifies the weak gene signal corresponding to the spot, and the variance gives the measure of the undesired binding that causes fluctuation in the measurement. We propose a foreground-signal and shape-estimation algorithm using the Gibbs sampling method. We compare our developed algorithm with the existing Mann–Whitney (MW)- and expectation maxi-mization (EM)/iterated conditional modes (ICM)-based methods. Our method outperforms the existing methods with consider-ably smaller mean-square error (MSE) for all signal-to-noise ratios (SNRs) in computer-generated images and gives better qualitative results in low-SNR real-data images. Our method is computationally relatively slow because of its inherent sampling operation and hence only applicable to very noisy-spot images. In a realistic example using our method, we show that the gene-signal fluctuations on the estimated foreground are better observed for the input noisy images with relatively higher undesired bindings. Index Terms—cDNA microarray, Gibbs sampling, low PMT voltage image, spot segmentation