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What can Ribo-seq, immunopeptidomics, and proteomics tell us about the non-canonical proteome?

Title: What can Ribo-seq, immunopeptidomics, and proteomics tell us about the non-canonical proteome?
Authors: Prensner, J.R.; Abelin, J.G.; Kok, L.W.; Clauser, K.R.; Mudge, J.M.; Ruiz-Orera, J.; Bassani-Sternberg, M.; Moritz, R.L.; Deutsch, E.W.; van Heesch, S.
Publisher Information: American Society for Biochemistry and Molecular Biology
Publication Year: 2023
Collection: Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository
Subject Terms: Cardiovascular and Metabolic Diseases; Topic 1: Genes; Cells and Cell-Based Medicine
Description: Ribosome profiling (Ribo-seq) has proven transformative for our understanding of the human genome and proteome by illuminating thousands of non-canonical sites of ribosome translation outside of the currently annotated coding sequences (CDSs). A conservative estimate suggests that at least 7,000 non-canonical open reading frames (ORFs) are translated, which, at first glance, has the potential to expand the number of human protein-coding sequences by 30%, from ∼19,500 annotated CDSs to over 26,000. Yet, additional scrutiny of these ORFs has raised numerous questions about what fraction of them truly produce a protein product and what fraction of those can be understood as proteins according to conventional understanding of the term. Adding further complication is the fact that published estimates of non-canonical ORFs vary widely by around 30-fold, from several thousand to several hundred thousand. The summation of this research has left the genomics and proteomics communities both excited by the prospect of new coding regions in the human genome, but searching for guidance on how to proceed. Here, we discuss the current state of non-canonical ORF research, databases, and interpretation, focusing on how to assess whether a given ORF can be said to be "protein-coding".
Document Type: article in journal/newspaper
File Description: application/pdf; other
Language: English
Relation: https://edoc.mdc-berlin.de/id/eprint/23670/1/23670oa.pdf; https://edoc.mdc-berlin.de/id/eprint/23670/7/23670suppl.zip; What can Ribo-seq, immunopeptidomics, and proteomics tell us about the non-canonical proteome? Prensner, J.R., Abelin, J.G., Kok, L.W., Clauser, K.R., Mudge, J.M., Ruiz-Orera, J., Bassani-Sternberg, M., Moritz, R.L., Deutsch, E.W. and van Heesch, S. Molecular & Cellular Proteomics 22 (9): 100631. September 2023; PMID:37572790; https://doi.org/10.1016/j.mcpro.2023.100631
DOI: 10.1016/j.mcpro.2023.100631
Availability: https://edoc.mdc-berlin.de/id/eprint/23670/; https://edoc.mdc-berlin.de/23670/; https://doi.org/10.1016/j.mcpro.2023.100631
Rights: cc_by_4
Accession Number: edsbas.4798A69D
Database: BASE