We grouped gene-level synonymous probesets according to gene ID (gene-level), and protein-level ones according to IPI ID (protein-level). Additionally, probesets corresponding to a single protein according to NetAffx probeset-protein mapping tables (see Materials) are grouped as 'Affy-protein' level synonymous probesets. In the case of the HG-U133A array, we included a fourth level, the 'Harbig-protein level', for comparison. The Harbig-protein level reflects the probeset-protein association transformed from a recent alternative annotation of the Affymetrix U133 plus 2.0 array [14] , also proposed in a transcript-level perspective. The downloaded annotation file mapped 33,579 probesets to 287,791 GenBank mRNA accessions, among which 21,669 were found on HG-U133A array, mapped to 186,085 GenBank mRNA accessions. The probeset-mRNA associations related to HG-U133A array were further linked to IPI IDs, finally giving rise to 26,960 probeset-IPI mapping relationships among which 12,146 were one-to-one. The following treatments were the same as those implemented to the standard gene-level annotation, the NetAffx Protein annotations, and our novel annotations. 30 and 28 expression datasets were selected from GEO respectively for MOE430A_2 and HG-U133A, and the original intensity data within each GEO dataset (GDS) were transformed to log 2 base and normalized to a constant median across all samples. For a synonymous group, if the expression values of all probesets in all samples were no larger than the constant median value, the probesets in this group were regarded not moderately expressed, and their expression profiles not informative enough. Therefore, we only kept the synonymous groups with at least one expression value above the constant median value, similar to the filtering procedure used by Tian et al. [62] . For the remaining synonymous groups, Pearson correlation coefficients (PCCs) were calculated for the expression profiles of each probeset pair. The minimum value of these PCCs was taken as a measurement of the expression coherence of this group. We used the minimum aggregation because the gene level synonymous probesets gave rise to within-protein PCCs (which are theoretically higher) and across-protein PCCs (which are theoretically lower), and the former was identical to the result of the protein-level synonymous group. In such a setting, the maximum did not result in any difference, and the average aggregation was not as sensitive as the minimum in terms of differentiating the two groups, so we adopted the minimum aggregation.