ORFeus: a computational method to detect programmed ribosomal frameshifts and other non-canonical translation events

Abstract

Abstract Background In canonical protein translation, ribosomes initiate translation at a specific start codon, maintain a single reading frame throughout elongation, and terminate at the first in-frame stop codon. However, ribosomal behavior can deviate at each of these steps, sometimes in a programmed manner. Certain mRNAs contain sequence and structural elements that cause ribosomes to begin translation at alternative start codons, shift reading frame, read through stop codons, or reinitiate on the same mRNA. These processes represent important translational control mechanisms that can allow an mRNA to encode multiple functional protein products or regulate protein expression. The prevalence of these events remains uncertain, due to the difficulty of systematic detection. Results We have developed a computational model to infer non-canonical translation events from ribosome profiling data. Conclusion ORFeus identifies known examples of alternative open reading frames and recoding events across different organisms and enables transcriptome-wide searches for novel events.

Keywords

• Non-canonical ORF
• Alternative ORF
• Ribosome profiling
• HMM