Exploiting blank spots for model-based background correction in discovering genes with DNA array data

Abstract

Motivated by a real data set deriving from a study on the genetic determinants of the behavior of Mycobacterium tuberculosis (MTB) hosted in macrophage, we take advantage of the presence of control spots and illustrate modelling issues for background correction and the ensuing empirical findings resulting from a Bayesian hierarchical approach to the problem of detecting differentially expressed genes. We prove the usefulness of a fully integrated approach where background correction and normalization are embedded in a single model-based framework, creating a new tailored model to account for the peculiar features of DNA array data where null expressions are planned by design. We also advocate the use of an alternative normalization device resulting from a suitable reparameterization. The new model is validated by using both simulated and our MTB data. This work suggests that the presence of a substantial fraction of exact null expressions might be the effect of an imperfect background calibration and shows how this can be suitably re-calibrated with the information coming from control spots. The proposed idea can be extended to all experiments in which a subset of genes whose expression levels can be ascribed mainly to background noise is planned by design.