A major focus after the completion of many genome sequencing projects in how the genes encoded in the genome are expressed at the messenger RNA (transcriptomics) and protein (proteomics) levels. Expression Proteomics is concerned with correlating cellular protein changes with cell behavioral changes. A typical question is: what protein changes correlate with the transformation of a normal cell into a cancerous cell? We have developed an approach that greatly accelerates the discovery of these protein changes. There are several computational challenges that need to be met to reach the full potential of this methodology: (1) automated detection of protein changes, (2) expanding the sensitivity range of protein detection and (3) data handling and management. The current protein detection technology outstrips our ability to identify the genes that encode low-abundance proteins of interest. We have embarked on developing a novel technology to overcome this barrier. Our first step was to formalize an idealized version of the problem in a well-known setting of set-covering problems, and to exploit the special structure to make our solution strategies computationally feasible. Our second step has been to perform computer simulations to model a more robust version of the problem including errors that is also somewhat more universal in its design. Jon will describe the biological context and framework of our new approach while Ravi will elaborate on the two models and solution strategies that we are developing. We will be describing joint work with Bjarni Halldorsson, a doctoral student in the ACO program in Mathematics, who is currently supported by a Merck Computational Biology Graduate Fellowship.