{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:44:53Z","timestamp":1792784693031,"version":"4.5.0"},"reference-count":63,"publisher":"American Chemical Society (ACS)","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"Postgraduate Research & Practice Innovation Program of Jiangsu Province","doi-asserted-by":"publisher","award":["26CXJH7401"],"award-info":[{"award-number":["26CXJH7401"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Natural Science Research Start-up Foundation of Recruiting Talents of Nanjing University of Posts and Telecommunications","doi-asserted-by":"publisher","award":["NY223062"],"award-info":[{"award-number":["NY223062"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/043bpky34","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/na","name":"Natural Science Foundation of Nanjing University of Posts and Telecommunications","doi-asserted-by":"publisher","award":["NY224158"],"award-info":[{"award-number":["NY224158"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/043bpky34","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genetic variants in untranslated regions (UTRs) can alter post-transcriptional regulation, yet functional interpretation remains difficult because regulatory mechanisms differ between 5\u2032UTR and 3\u2032UTR contexts and are not fully captured by generic noncoding-variant scores. We developed UTR-FNex, an interpretable machine-learning framework for prioritizing candidate functional variants in both UTR regions. We first constructed MetaUTR, a harmonized resource of approximately 200,000 UTR variant loci, and derived model-development sets containing 14,627 3\u2032UTR and 3533 5\u2032UTR variants after confidence-based filtering. UTR-FNex integrates region-specific sequence, RNA-structure, regulatory-motif, miRNA, conservation, and DNABERT-derived allele representations, with a neural feature enhancement (NFE) module providing additional interaction summaries. Across 10 repeated random hold-outs, mean AUROCs were 0.876 for 3\u2032UTR and 0.974 for 5\u2032UTR. Under gene-grouped evaluation, AUROCs decreased to 0.769 and 0.672, respectively, indicating substantial context dependence, especially for 5\u2032UTR. In an external prostate-cancer 3\u2032UTR cohort, UTR-FNex achieved an AUROC of 0.720 (95% CI 0.690\u20130.750), compared with 0.696 (95% CI 0.660\u20130.733) for FunUV; however, FunUV achieved higher AUPRC and stronger top-k enrichment. A TP53 rs78378222 case study connected model sensitivity to a known polyadenylation-signal context, whereas RNAfold-derived differences were window-dependent and were treated as exploratory. These results support UTR-FNex as a multimodal prioritization framework while defining important limits in cross-gene and cross-source generalization. Source code is available at https:\/\/github.com\/liyaning233\/UTR-FNex, and MetaUTR is deposited at 10.5281\/zenodo.19719670.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01582","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:01:45Z","timestamp":1790596905000},"page":"12989-13004","source":"Crossref","is-referenced-by-count":0,"title":["Untranslated Region-FNex:\nAn Integrative Multimodal\nFramework for Functional Untranslated Region Variant Prioritization"],"prefix":"10.1021","volume":"66","author":[{"given":"Yaning","family":"Li","sequence":"first","affiliation":[{"name":"Jiangsu University of Science and Technology , , 666 Changhui Road , ,","place":["Zhenjiang, China, 212100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ge","sequence":"additional","affiliation":[{"name":"Nanjing University of Posts & Telecommunications , , 9 Wenyuan Road , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Pan","sequence":"additional","affiliation":[{"name":"Jiangsu University of Science and Technology , , 666 Changhui Road , ,","place":["Zhenjiang, China, 212100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3197-3523","authenticated-orcid":true,"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu University of Science and Technology , , 666 Changhui Road , ,","place":["Zhenjiang, China, 212100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"4","key":"2026101208065692200_cit1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.trecan.2019.02.011","article-title":"The Untranslated Regions of mRNAs in Cancer","volume":"5","author":"Schuster","year":"2019","journal-title":"Trends Cancer"},{"issue":"6","key":"2026101208065692200_cit2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1101\/gr.242552.118","article-title":"A massively parallel\n3\u2032 UTR reporter assay reveals relationships between nucleotide\ncontent, sequence conservation, and mRNA destabilization","volume":"29","author":"Litterman","year":"2019","journal-title":"Genome Res."},{"issue":"13\u201314","key":"2026101208065692200_cit3","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1101\/gad.351649.124","article-title":"A developmental mechanism\nto regulate alternative polyadenylation in an adult stem cell lineage","volume":"38","author":"Gallicchio","year":"2024","journal-title":"Genes Dev."},{"issue":"12","key":"2026101208065692200_cit4","doi-asserted-by":"publisher","first-page":"gkaf568","DOI":"10.1093\/nar\/gkaf568","article-title":"The quantitative impact of 3\u2032UTRs\non gene expression","volume":"53","author":"West","year":"2025","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"2026101208065692200_cit5","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/nrm.2017.103","article-title":"Functional 5\u2032\nUTR mRNA structures in eukaryotic\ntranslation regulation and how to find them","volume":"19","author":"Leppek","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"2026101208065692200_cit6","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1146\/annurev-genet-120116-024704","article-title":"Regulation\nby 3\u2032-Untranslated Regions","volume":"51","author":"Mayr","year":"2017","journal-title":"Annu. Rev.\nGenet."},{"issue":"10","key":"2026101208065692200_cit7","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1007\/s00439-021-02395-9","article-title":"Disease-associated\nhuman genetic\nvariation through the lens of precursor and mature RNA structure","volume":"141","author":"Waldern","year":"2022","journal-title":"Hum. 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