High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant sub-pathways in relation to the unfolding of the biological process under study.
Bioinformatics | Computational Biology
Telesca, Donatello; Muller, Peter; Kornblau, Steven; Suchard, Marc; and Ji, Yuan, "Modeling Protein Expression and Protein Signaling Pathways" (December 2011). COBRA Preprint Series. Working Paper 87.