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Articles by Jonathan Mudge
Expanding the human proteome with microproteins and peptideins
Abstract A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states1,2,3, with major implications for biomedical science.
Community benchmarking and evaluation of human unannotated microprotein detection by mass spectrometry based proteomics - Nature Communications
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Abstract Thousands of short open reading frames (sORFs) are translated outside of annotated coding sequences. Recent studies have pioneered searching for sORF-encoded microproteins in mass spectrometry (MS)-based proteomics and peptidomics datasets. Here, we assessed literature-reported MS-based identifications of unannotated human proteins. We find that studies vary by three orders of magnitude in the number of unannotated proteins they report.
By Aaron Wacholder, Eric Deutsch, Leron W. Kok, Jiwon Lee, James Wright, Kevin Jiang Verified, Francis Bourassa, Michal Bassani-Sternberg, Sonia Chothani, Ivo Fierro-Monti, Kris Gevaert, Norbert Hubner, Jonathan Mudge, Jorge Ruiz-Orera, Juan Antonio Vizcaino, John R. Prensner, Marie A. Brunet, Thomas Martinez, Sarah A. Slavoff, Xavier Roucou, Jyoti Choudhary, Robert L. Moritz
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Nature
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Programmed ribosomal frameshifting during PLEKHM2 mRNA decoding generates a constitutively active proteoform that supports myocardial function
Abstract Programmed ribosomal frameshifting is a process where a proportion of ribosomes change their reading frame on an mRNA. While frameshifting is commonly used by viruses, very few phylogenetically conserved examples are known in nuclear encoded genes. Here, we report a +1 frameshifting event during decoding of the human gene PLEKHM2 that provides access to a second internally overlapping ORF.
High-quality peptide evidence for annotating non-canonical open reading frames as human proteins
Abstract A major scientific drive is to characterize the protein-coding genome as it provides the primary basis for the study of human health. But the fundamental question remains: what has been missed in prior genomic analyses? Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states, with major implications for proteomics, genomics, and clinical science.
Ribosome decision graphs for the representation of eukaryotic RNA translation complexity
1 1School of Biochemistry and Cell Biology, University College Cork, Cork T12 K8AF, Ireland; 2SFI Centre for Research Training in Genomics Data Science, University College Cork, Cork T12 K8AF, Ireland; 3Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland; 4Computational Biology Unit, Department of Informatics, University of Bergen, NO-5020 Bergen, Norway; 5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome...
Addendum: Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals - Nature Communications
Addendum to: Nature Communications https://doi.org/10.1038/s41467-022-35595-6, published online 23 December 2022 We would like to make readers aware that after the publication of the original article, we found that the parameters for PhyloCSF score calculation were obtained for an alignment other than 120 mammals. This made our analysis less sensitive than intended.
Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity
Abstract The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, both within annotated protein-coding and non-coding regions. The biological significance of this translation is a matter of intensive investigation.
Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals - Nature Communications
Abstract The synthesis of most proteins begins at AUG codons, yet a small number of non-AUG initiated proteoforms are also known. Here we analyse a large number of publicly available Ribo-seq datasets to identify novel, previously uncharacterised non-AUG proteoforms using Trips-Viz implementation of a novel algorithm for detecting translated ORFs. In parallel we analyse genomic alignment of 120 mammals to identify evidence of protein coding evolution in sequences encoding potential extensions.
Standardized annotation of translated open reading frames - Nature Biotechnology
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To the Editor — Ribosome profiling (Ribo-seq) has extended our understanding of the translational ‘vocabulary’ of the human genome, uncovering thousands of open reading frames (ORFs) within long noncoding RNAs (lncRNAs) and presumed untranslated regions (UTRs) of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs because of uncertainties about their experimental reproducibility and physiological roles.
By Jonathan Mudge, Jorge Ruiz-Orera, John R. Prensner, Marie A. Brunet, Irwin Jungreis, Jose Gonzalez, José González Verified, Thomas Martinez, Yucheng Yang, Pavel V. Baranov, Ariel A. Bazzini, Elspeth A. Bruford, Anne-Ruxandra Carvunis, Jin Chen, Eric Deutsch, Paul Flicek, Norbert Hubner, Nicholas T. Ingolia, Manolis Kellis, Uwe Ohler, Xavier Roucou, Alan Saghatelian, Sebastiaan van Heesch, Ferriol Calvet, Michele Magrane, Jana Felicitas Schulz, Juan Pablo Couso, Robert L. Moritz
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Nature
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Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals
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Functional signatures of evolutionarily young CTCF binding sites
Abstract Background The introduction of novel CTCF binding sites in gene regulatory regions in the rodent lineage is partly the effect of transposable element expansion, particularly in the murine lineage. The exact mechanism and functional impact of evolutionarily novel CTCF binding sites are not yet fully understood.
Nearly all new protein-coding predictions in the CHESS database are not protein-coding
Nearly all new protein-coding predictions in the CHESS database are not protein-coding Irwin Jungreis, Michael L. Tress, Jonathan Mudge, Cristina Sisu, Toby Hunt, Rory Johnson, Barbara Uszczynska-Ratajczak, Julien Lagarde, James Wright, Paul Muir, Mark Gerstein, Roderic Guigo, Manolis Kellis, Adam Frankish, Paul Flicek, The GENCODE Consortium bioRxiv 360602; doi: https://doi.org/10.1101/360602
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