Proteomics Can Rise to the Challenge of Pseudogenes’ Coding Nature

Throughout the past decade, technological advances in genomics and transcriptomics have revealed pervasive translation throughout mammalian genomes. These putative proteins are usually excluded from proteomics analyses, as they are absent from common protein repositories. A sizable portion of these noncanonical proteins is translated from pseudogenes. Pseudogenes are commonly termed defective copies of coding genes unable to produce proteins. Here, we suggest that proteomics can help in their annotation. First, we define important terms and review specific examples underlining the caveats in pseudogene annotation and their coding potential. Then, we will discuss the challenges inherent to pseudogenes that have thus far rendered complex their confidence in omics data. Finally, we identify recent developments in experimental procedures, instrumentation, and computational methods in proteomics that put the field in a unique position to solve the pseudogene annotation conundrum.