{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kaschta D"],"funding":["M.S. is a DZHK principal investigator and is supported by grants from the Deutsche Forschungsgemeinschaft","Universität zu Lübeck"],"pagination":["100"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12445032"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["<h4>Background</h4>Short-read genome sequencing (GS) is among the most comprehensive genetic testing methods available, capable of detecting single-nucleotide variants, copy-number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite its technical advantages, the full clinical utility of GS in real-world diagnostic settings remains to be fully established.<h4>Methods</h4>This study systematically compared singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) genetic testing in 416 patients with rare diseases in a blinded, prospective study. Three independent teams with divergent baseline expertise evaluated the diagnostic yield of GS as a unifying first-tier test and directly compared its variant detection ca"],"journal":["Genome medicine"],"pubmed_title":["Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis."],"pmcid":["PMC12445032"],"funding_grant_id":["(DFG; SP1532/13-1, SP1532/3-2 and SP1532/5-1)"],"pubmed_authors":["Franzenburg S","Wilson S","Nagel I","van der Ven AT","Hoffmann B","Handler K","Woitschach R","Kaschta D","Hornig N","Gehring B","Schlein C","Munchau A","Greiten B","Rosenstiel P","Yumiceba V","Herrmann G","Pozojevic J","Utermann-Thusing C","Berge V","Caliebe A","Spielmann M","Papingi D","Hellenbroich Y","Post C","Birgel F","Herget T","Schau-Romer K","Hoff K","Dalski A","Dittmar M","Lisfeld J","Rust F","Gaass F","Arriens V","Sreenivasan VKA","Wehnert J","Volk AE","Franke A","Loscher BS","Gembicki R","Grohte K","Muhle H","Bruggemann N","Recke A","Kautza-Lucht M","Rosler L","Hiort O","Penas EMM","Zuhlke C","Fuß J","Balachandran S","Harder L","Vater I","Margraf NG","Toutouna L","Al-Tawil M","Salewski MB","Liegmann AS","Meyenborg M","Mollring A","Nommels H","Huning I","Baumer T","Kohler J","Roberts K","Hanker B","Poggenburg I"],"additional_accession":[]},"is_claimable":false,"name":"Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis.","description":"<h4>Background</h4>Short-read genome sequencing (GS) is among the most comprehensive genetic testing methods available, capable of detecting single-nucleotide variants, copy-number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite its technical advantages, the full clinical utility of GS in real-world diagnostic settings remains to be fully established.<h4>Methods</h4>This study systematically compared singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) genetic testing in 416 patients with rare diseases in a blinded, prospective study. Three independent teams with divergent baseline expertise evaluated the diagnostic yield of GS as a unifying first-tier test and directly compared its variant detection ca","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T14:36:09.991Z","creation":"2026-04-28T03:11:42.156Z"},"accession":"S-EPMC12445032","cross_references":{"pubmed":["40963120"],"doi":["10.1186/s13073-025-01516-7"]}}