Probabilistic Inference of Alternative Splicing Events in Microarray Data

Alternative splicing (AS) is an important and frequent step in mammalian gene expression that allows a single gene to specify multiple products, and is crucial for the regulation of fundamental biological processes. The extent of AS regulation, and the mechanisms involved, are not well understood. We have developed a custom DNA microarray platform for surveying AS levels on a large scale. We present here a generative model for the AS Array Platform (GenASAP) and demonstrate its utility for quantifying AS levels in different mouse tissues. Learning is performed using a variational expectation maximization algorithm, and the parameters are shown to correctly capture expected AS trends. A comparison of the results obtained with a well-established but low through-put experimental method demonstrate that AS levels obtained from GenASAP are highly predictive of AS levels in mammalian tissues.