ArticlePLoS biology2023
Biological factors and statistical limitations prevent detection of most noncanonical proteins by mass spectrometry.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- Activity-dependent ribosome profiling reveals the landscape of canonical and non-canonical translation in brain tissue.Nature communications · 2026Article
- Cervical mucus proteomics approach for swamp buffalo secreted fertility biomarker identification.Journal of veterinary research · 2026Article
- A Proteogenomic Approach to Discover Novel lncRNA-Derived Microproteins and Their Potential Clinical Utility in Hepatocellular Carcinoma.Molecular & cellular proteomics : MCP · 2026Article
- Integrating Spatial Proteogenomics in Cancer Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mistranslation suppresses mistranscription in eukaryotes.Nature communications · 2026Article
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- Community benchmarking and evaluation of human unannotated microprotein detection by mass spectrometry based proteomics.Nature communications · 2026Article
- The 'non-conventional' peptidome: A new layer in plant regulatory mechanisms.Plant communications · 2025Review
- The impact of ribosome association on lncRNA stability: a new layer of post-transcriptional control?Biochemical Society transactions · 2025Review
- De Novo Gene Emergence: Summary, Classification, and Challenges of Current Methods.Genome biology and evolution · 2025Review
- Propensity for proto-gene emergence in bacteria.Genome biology · 2025Article
- Functional analysis and transcriptional profiling of non-coding RNAs in yeast.The Biochemical journal · 2025Review
- Comprehensive profiling of ribo-seq detected small sequences in yeast reveals robust conservation patterns and their potential mechanisms of origin.BMC genomics · 2025Article
- Detection and Quantitation of Small Proteins Using Mass Spectrometry.Molecular & cellular proteomics : MCP · 2025Article
- High-quality peptide evidence for annotating non-canonical open reading frames as human proteins.bioRxiv : the preprint server for biology · 2025Article
- Proteogenomics-enabled discovery of novel small open reading frame (sORF)-encoded polypeptides in human and mouse tissues.Nucleic acids research · 2025Article
- Core gene set of the speciesbioRxiv : the preprint server for biology · 2025Article
- Saccharomyces Genome Database: advances in genome annotation, expanded biochemical pathways, and other key enhancements.Genetics · 2025Article
- The hidden bacterial microproteome.Molecular cell · 2025Article
Corrections and comments
- Update of
Authors and funding
2 authors.
Funding
Abstract
Ribosome profiling experiments indicate pervasive translation of short open reading frames (ORFs) outside of annotated protein-coding genes. However, shotgun mass spectrometry (MS) experiments typically detect only a small fraction of the predicted protein products of this noncanonical translation. The rarity of detection could indicate that most predicted noncanonical proteins are rapidly degraded and not present in the cell; alternatively, it could reflect technical limitations. Here, we leveraged recent advances in ribosome profiling and MS to investigate the factors limiting detection of noncanonical proteins in yeast. We show that the low detection rate of noncanonical ORF products can largely be explained by small size and low translation levels and does not indicate that they are unstable or biologically insignificant. In particular, proteins encoded by evolutionarily young genes, including those with well-characterized biological roles, are too short and too lowly expressed to be detected by shotgun MS at current detection sensitivities. Additionally, we find that decoy biases can give misleading estimates of noncanonical protein false discovery rates, potentially leading to false detections. After accounting for these issues, we found strong evidence for 4 noncanonical proteins in MS data, which were also supported by evolution and translation data. These results illustrate the power of MS to validate unannotated genes predicted by ribosome profiling, but also its substantial limitations in finding many biologically relevant lowly expressed proteins.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.