{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:26:35Z","timestamp":1772994395115,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The introduction of Next\u2010Generation Sequencing technologies in the clinics has improved rare disease diagnosis. Nonetheless, for very heterogeneous or very rare diseases, more than half of cases still lack molecular diagnosis. Novel strategies are needed to prioritize variants within a single individual. The Population Sampling Probability (PSAP) method was developed to meet this aim but only for coding variants in exome data. Here, we propose an extension of the PSAP method to the non\u2010coding genome called PSAP\u2010genomic\u2010regions. In this extension, instead of considering genes as testing units (PSAP\u2010genes strategy), we use genomic regions defined over the whole genome that pinpoint potential functional constraints. We conceived an evaluation protocol for our method using artificially generated disease exomes and genomes, by inserting coding and non\u2010coding pathogenic ClinVar variants in large data sets of exomes and genomes from the general population. PSAP\u2010genomic\u2010regions significantly improves the ranking of these variants compared to using a pathogenicity score alone. Using PSAP\u2010genomic\u2010regions, more than 50% of non\u2010coding ClinVar variants were among the top 10 variants of the genome. On real sequencing data from six patients with Cerebral Small Vessel Disease and nine patients with male infertility, all causal variants were ranked in the top 100 variants with PSAP\u2010genomic\u2010regions. By revisiting the testing units used in the PSAP method to include non\u2010coding variants, we have developed PSAP\u2010genomic\u2010regions, an efficient whole\u2010genome prioritization tool which offers promising results for the diagnosis of unresolved rare diseases.<\/jats:p>","DOI":"10.1002\/gepi.22593","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T09:34:44Z","timestamp":1727256884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PSAP\u2010Genomic\u2010Regions: A Method Leveraging Population Data to Prioritize Coding and Non\u2010Coding Variants in Whole Genome Sequencing for Rare Disease Diagnosis"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-5468","authenticated-orcid":false,"given":"Marie\u2010Sophie C.","family":"Ogloblinsky","sequence":"first","affiliation":[{"name":"Univ Brest, Inserm, EFS, UMR 1078, GGB Brest 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France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozan","family":"Ozisik","sequence":"additional","affiliation":[{"name":"INSERM, Marseille Medical Genetics (MMG) Aix Marseille University Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00efs","family":"Baudot","sequence":"additional","affiliation":[{"name":"INSERM, Marseille Medical Genetics (MMG) Aix Marseille University Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Tournier\u2010Lasserve","sequence":"additional","affiliation":[{"name":"Inserm, NeuroDiderot, Unit\u00e9 Mixte de Recherche Universit\u00e9 Paris Cit\u00e9 Paris France"},{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris Service de G\u00e9n\u00e9tique Mol\u00e9culaire Neurovasculaire, H\u00f4pital Saint\u2010Louis Paris 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