Splice variants in the proteome: a promising and challenging field to targeted drug discovery

•Many human genes are affected by alternative splicing.•There are several alternative spliced transcripts with their structures already solved.•Alternative splicing can be detected in different MS database searches.•Advances in computational approaches using transcriptome data in MS database search have been accomplished.•High-throughput transcriptomics and proteomics data are great sources for targeted drug discovery. The advent and improvement of high-throughput sequencing over the past decade leveraged the study of whole genomes and transcriptomes of different organisms at lower costs. In transcriptomics, RNA-Seq expands our capacity to understand gene expression in different tissues and pathologies, and how alternative splicing might affect the final protein sequence. Here, we discuss the association of using transcriptome and proteome high-throughput data to foster drug discovery. Using this innovative strategy, some research groups have already identified computationally predicted novel peptides derived from putative splice variants in experimental human proteome data. These discoveries provide new opportunities for targeted drug development.