There are two types of protein microarrays [3] . A 'functional protein microarray' contains a set of proteins individually produced and positioned in an addressable format on a microarray surface. Functional protein microarrays are useful for identifying binding activities or targets of modification enzymes. The first version of a proteome microarray was reported in 2001 and contained 5,800 yeast proteins with amino-terminal glutathione S-transferase (GST) tags printed on the array [4] . A second version of yeast protein microarrays was generated recently and contained 5,600 proteins with carboxy-terminal 6His-HA-ZZ domain tags [5] . Proteins from both collections were overexpressed, purified and spotted onto the protein microarrays. Global proteome studies were performed on these chips to understand various biological mechanisms. For example, 87 yeast kinases were examined for their substrates using yeast protein microarrays and over 4,200 in vitro substrates representing 1,325 unique proteins were identified [6] . Compared with the approximately 150 known in vivo kinase-substrate interactions, this global study served as an important first step for dissecting yeast signaling networks. In addition to searching for kinase substrates, proteome chips can be probed with labeled proteins, DNA, lipids, antibodies and many other molecules to search for interacting proteins [4, 7, 8] . Large amounts of data have been generated using protein microarrays, presenting significant challenges in developing robust methods to process the raw data and building reasonable biological hypotheses from the datasets.