Stable noncanonical peptides identified across five eukaryotes using ribosome profiling and ORF feature analysis (nature.com)

• PepScore model accurately predicts stable noncanonical peptides with AUROC 0.944.
• 4,812 human ncORFs have high PepScore (>0.6); most are species-specific and poorly conserved.
• uSLC35A4 and iPGRMC1 microproteins localize to mitochondria and have functional roles in cell growth and signaling.

"Researchers at Northwestern University used ribosome profiling data from five eukaryotic species (human, mouse, zebrafish, worm, yeast) to identify thousands of translated noncanonical open reading frames (ncORFs). They developed a logistic regression model, PepScore, that integrates ORF length, conservation, and domain content to predict peptide stability. Ectopic expression of 29 uORFs validated the model; high-PepScore peptides were stable and often localized to mitochondria. The study also characterized uSLC35A4 and iPGRMC1 microproteins, revealing roles in mitochondrial function."