MEGUERDITCHIAN, Caroline; BAUX, David; LUDWIG, Thomas E; GENIN, Emmanuelle; TREGOUET, David-Alexandre; SOUKARIEH, Omar

doi:10.1093/nargab/lqaf017

MEGUERDITCHIAN, Caroline
Bordeaux population health [BPH]

BAUX, David

LUDWIG, Thomas E

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Article de revue

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NAR Genomics and Bioinformatics. 2025-03-01, vol. 7, n° 1, p. lqaf017

Résumé en anglais

Non-canonical small open reading frames (sORFs) are among the main regulators of gene expression. The most studied of these are upstream ORFs (upORFs) located in the 5,-untranslated region (UTR) of coding genes. Internal ORFs (intORFs) in the coding sequence and downstream ORFs (dORFs) in the 3,UTR have received less attention. Different bioinformatics tools permit the prediction of single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool predicts variants altering non-canonical translation initiation sites and those altering intORFs or dORFs. We propose an upgrade of our MORFEE bioinformatics tool to identify SNVs that may alter all types of sORFs in coding transcripts from a VCF file. Moreover, we generate an exhaustive catalog, named MORFEEdb, reporting all possible SNVs altering existing upORFs or creating new ones in human transcripts, and provide an R script for visualizing the results. MORFEEdb has been implemented in the public platform Mobidetails. Finally, the annotation of ClinVar variants with MORFEE reveals that > 45% of UTR-SNVs can alter upORFs or dORFs. In conclusion, MORFEE and MORFEEdb have the potential to improve the molecular diagnosis of rare human diseases and to facilitate the identification of functional variants from genome-wide association studies of complex traits. © The Author(s) 2025.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/206359

DOI

http://dx.doi.org/10.1093/nargab/lqaf017

Project ANR

Etude du caractère pathogène de variants créant des cadres de lecture ouverts en amont de la séquence codante de l'endogline - Nouvelles perspectives thérapeutiques pour la maladie du Rendu-Osler - ANR-23-CE17-0042
Vaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutique - ANR-23-IAHU-0001

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5,UTRs

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Résumé en anglais

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