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330: Base by Base Ep.330 — 5ULTRA: Mapping 5′ UTR variants that alter protein translation

30 Mar 2026

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Chaldebas M et al., The American Journal of Human Genetics - Chaldebas et al. present 5ULTRA, a computational pipeline that integrates uORF databases, Kozak-motif features, splicing prediction, and a random-forest score to detect and prioritize 5′ UTR variants predicted to alter protein translation. The score correlates with proteomic and MPRA measures and is applied to population, somatic, GWAS, and rare-disease datasets to nominate candidate functional variants. Key terms: 5' UTR, uORF, Kozak motif, translation regulation, machine learning. Study Highlights:The authors developed 5ULTRA to annotate SNVs, indels, and splicing variants that create/disrupt uORFs or alter Kozak strength, integrating comprehensive uORF databases and SpliceAI. A random-forest 5ULTRA score trained on HGMD and gnomAD distinguishes likely translation-impacting variants and achieved strong cross-validation performance and AUC = 0.82 on an independent ClinVar test. The score correlates with cis-pQTL effect sizes (Spearman rho = 0.57) and with MPRA ribosome-load measurements (rho = 0.78). Genome-wide screening found thousands of candidate variants, highlighted rare/conserved signals in disease genes, and nominated examples in cancer, GWAS loci, and rare infections. Conclusion:5ULTRA provides a validated, transcript-aware framework to detect and prioritize 5′ UTR variants that modulate translation, offering mechanistic hypotheses for noncoding variant interpretation in rare disease, cancer, and complex-trait genetics; the tool and data are publicly available under a CC BY license. QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-30.Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.Factual QC score: 10/10.Metadata QC score: 10/10.Supported core claims: 8.Claims flagged for review: 0.Metadata checks passed: 4.Metadata issues found: 0.QC result: Pass. Music:Enjoy the music based on this article at the end of the episode. Article title:Genome-wide detection of human 5′ UTR variants that impact protein translation First author:Chaldebas M Journal:The American Journal of Human Genetics DOI:https://doi.org/10.1016/j.ajhg.2026.02.020 Reference:Chaldebas M, Ponsin K, Bohlen J, et al. Genome-wide detection of human 5′ UTR variants that impact protein translation. The American Journal of Human Genetics. 2026;113:1–19. https://doi.org/10.1016/j.ajhg.2026.02.020 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/5ultra-5utr-variants Chapters (00:00:08) - Genome Wide Detection of Human 5 UTR Variants(00:06:41) - How a Deep Learning Algorithm Can Identify Dangerous Human Variants(00:12:35) - 5 Ultra: The computational genetics of cancer(00:18:46) - How to decode the secrets of the human genome

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13:00H | 21 DIC 2025 | Fin de Semana

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Base by Base

330: Base by Base Ep.330 — 5ULTRA: Mapping 5′ UTR variants that alter protein translation

This episode hasn't been transcribed yet

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13:00H | 21 DIC 2025 | Fin de Semana

10:00H | 21 DIC 2025 | Fin de Semana

12:00H | 20 DIC 2025 | Fin de Semana

2ª PARTE | 06 ENE 2026 | EL PARTIDAZO DE COPE

3ª PARTE | 22 ENE 2026 | EL PARTIDAZO DE COPE

3ª PARTE | 04 MAR 2026 | EL PARTIDAZO DE COPE

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