Microproteins and peptideins expand the human proteome

What the study found: The study found that about 25% of a set of 7,264 noncoding open reading frames (ncORFs) gave rise to detectable peptides in a large-scale proteomics analysis. The authors also introduced an annotation framework for ncORF-encoded microproteins as human proteins and defined a new concept, "peptideins," for microproteins with indeterminate potential as functional proteins.
Why the authors say this matters: The authors conclude that these results advance biomedical discovery for understudied components of the human proteome, and they present public research tools supported by GENCODE and PeptideAtlas. They also suggest that their evolutionary analysis may help probe the biological implications of peptideins.
What the researchers tested: The researchers analyzed 95,520 proteomics experiments to build a consensus landscape of protein-level evidence for ncORFs. They created an evolutionary analysis approach called ORF relative branch length (ORBL) and used it to examine constraint among ncORF-derived peptides, and they characterized one peptidein from the OLMALINC long non-coding RNA.
What worked and what didn't: The large-scale proteomics analysis detected peptides from roughly one quarter of the ncORFs examined. The ORBL analysis showed that evolutionary constraint is common and is associated with observation of ncORF-derived peptides. The study also identified a pan-essential cellular phenotype for one peptidein from OLMALINC.
What to keep in mind: The abstract does not describe detailed limitations beyond noting that peptideins have indeterminate potential as functional proteins. The results are limited to the ncORFs, proteomics data, and specific example discussed in the abstract.

Key points

• About 25% of 7,264 ncORFs produced detectable peptides in 95,520 proteomics experiments.
• The authors introduced an annotation framework for ncORF-encoded microproteins as human proteins.
• They defined "peptideins" as microproteins with indeterminate potential as functional proteins.
• ORF relative branch length (ORBL) was used to study evolutionary constraint in ncORFs.
• Evolutionary constraint was reported as common and associated with ncORF-derived peptide observation.
• One peptidein from the OLMALINC long non-coding RNA showed a pan-essential cellular phenotype.