We noticed that in these genome-scale studies PPI information was always first converted to gene pairs, after which the Pearson correlations of the probeset pairs corresponding to the gene pairs were evaluated. That is, the analysis targets were expanded from real interacting protein pairs to all possible cross-gene protein pairs for which interaction may not always exist. As illustrated in Figure 3 , suppose we have gene a (abbreviated to Ga) and gene b (Gb), with Ga encoding protein a1 (Pa1) and protein a2 (Pa2), Gb encoding protein b1 (Pb1) and protein b2 (Pb2). Among these protein variants, only proteins Pa2 and Pb1 interact with each other, while the other three possible cross-gene interactions, including Pa1-Pb1, Pa1-Pb2 and Pa2-Pb2, do not really happen. The four probesets, Pst_a1, Pst_a2, Pst_b1, and Pst_b2, recognize transcript variants Ta1, Ta2, Tb1 and Tb2 respectively, producing proteins Pa1, Pa2, Pb1 and Pb2. In the conventional genome-scale studies mentioned above, besides the probeset pair (Pst_a2, Pst_b1) corresponding to the real interacting protein pair, the other three cross-gene pairs, (Pst_a1, Pst_b1), (Pst_a1, Pst_b2) and (Pst_a2, Pst_b2), were also included, which would blunt the expression cor-Expression profiles of synonymous probesets Figure 2 Expression profiles of synonymous probesets. A) Three probesets on the array MOE430A_2 are associated with the mouse gene Prlr. Probeset 1448556_at correlates to protein IPI00321091, or PRL-R3; probesets 1421382_at and 1451844_at both point to protein IPI00408593, or PRL-R2. GEO dataset GDS1277 was analyzed. B) Three probesets on the array MOE430A_2 are associated with the mouse gene Alg14. Probesets 149114_at and 149115_at both point to protein IPI00132168; probeset 1419116_at correlates to protein IPI00405947. GEO dataset GDS1076 was analyzed.