Probabilistic discovery of overlapping cellular processes and their regulation

摘要

Many of the functions carried out by a living cell are regulated at the transcriptional level, to ensure that genes are expressed when they are needed. Thus, to understand biological processes, it is thus necessary to understand the cell's transcriptional network. In this paper, we propose a novel probabilistic model of gene regulation for the task of identifying overlapping biological processes and the regulatory mechanism controlling their activation. A key feature of our approach is that we allow genes to participate in multiple processes, thus providing a more biologically plausible model for the process of gene regulation. We present an algorithm to learn this model automatically from data, using only genome-wide measurements of gene expression as input. We compare our results to those obtained by other approaches, and show significant benefits can be gained by modeling both the organization of genes into overlapping cellular processes and the regulatory programs of these processes. Moreover,our method successfully grouped genes known to function together, recovered many regulatory relationships that are known in the literature, and suggested novel hypotheses regarding the regulatory role of previously uncharacterized proteins.