Isoform and non-isoform specific peptides . (A) Two protein isoforms (1 and 2) from an alternatively spliced gene that differ by a local polymorphism (inclusion/exclusion grey rectangle) yield two different peptide sets (Isoform 1: p1, p2, p4; Isoform 2: p1, p3, p4) when digested. While peptides p1 and p4 are non-specific because they map to both isoforms, peptides p2 and p3 are specific for isoform 1 and isoform 2, respectively. (B) The gene structures (exons correspond to the rectangles and the lines connecting them represent the introns) underlying these protein isoforms show that the AS event that is associated with the variable protein region is an exon-skipping event. In order to confirm the contribution of this specific exon-skipping event to the proteome diversity, both peptides p2 and p3 need to be identified. The dotted line indicates that p3 spans an exon/exon junction. (C) The initial peptide populations that are constructed for the in silico AS detection experiments differ under the two probability assumptions that are used in this study. Under the "equal pooling probability" assumptions, the initial peptide population consists of only unique peptides. Therefore the population contains only four different peptides. Under the "equal expression" assumption, the isoforms are represented by equal numbers of molecules prior to digestion. As a result, non-specific peptides are more abundant than isoform specific peptides.