Analyzing alternate translation

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A single amino acid substitution (AAS) can substantially alter protein function and even cause disease. These protein sequence changes can arise from genetic mutations, RNA editing or alternate translation — mRNA translation that deviates from the standard genetic code. AASs that result from alternate translation were once thought to be rare. However, a recent study by Tsour et al. has overturned this notion, demonstrating that such AASs are more pervasive than previously thought.

The team conducted a comprehensive analysis of paired proteomic, transcriptomic and genomic data from 1,094 human samples, including 6 cancer types and 26 healthy tissue types. They then created a predicted protein database based on transcriptomes and cross-referenced it against mass spectrometry proteomic data to identify modified peptides that arise from alternate translation. A rigorous filtering and validation pipeline enabled them to exclude interference from post-translational modifications and alternative reading frames. As a result, they identified 8,746 unique AASs mapping to 1,767 genes, most of which had not been previously predicted.