biostudies-literatureMendez-Vidal CInstituto de Salud Carlos IIIUniversidad de SevillaConsejería de Salud y Familias, Junta de AndalucíaFundación Isabel Gemio86https://www.ebi.ac.uk/biostudies/studies/S-EPMC11748347biostudies-literatureUnknown23(1)<h4>Background</h4>Despite the use of Next-Generation Sequencing (NGS) as the gold standard for the diagnosis of rare diseases, its clinical implementation has been challenging, limiting the cost-effectiveness of NGS and the understanding, control and safety essential for decision-making in clinical applications. Here, we describe a personalized NGS-based strategy integrating precision medicine into a public healthcare system and its implementation in the routine diagnosis process during a five-year pilot program.<h4>Methods</h4>Our approach involved customized probe designs, the generation of virtual panels and the development of a personalized medicine module (PMM) for variant prioritization. This strategy was applied to 6500 individuals including 6267 index patients and 233 NGS-based caJournal of translational medicineA genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice.PMC11748347FI19/00091FGEMIO-2019-01IMP-0009PI21-00244PEER-0470-2019P20_00887RH-0049-2021PEER-0501-2019PI19-01550PI22-01428Mendez-Vidal CAntinolo GBorrego SGonzalez-Del Pozo MDopazo JCarmona RMartin-Sanchez MBravo-Gil NFernandez-Suarez EPerez-Florido JFernandez-Rueda JLMarcos-Luque IFernandez RMMena MfalseA genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice.<h4>Background</h4>Despite the use of Next-Generation Sequencing (NGS) as the gold standard for the diagnosis of rare diseases, its clinical implementation has been challenging, limiting the cost-effectiveness of NGS and the understanding, control and safety essential for decision-making in clinical applications. Here, we describe a personalized NGS-based strategy integrating precision medicine into a public healthcare system and its implementation in the routine diagnosis process during a five-year pilot program.<h4>Methods</h4>Our approach involved customized probe designs, the generation of virtual panels and the development of a personalized medicine module (PMM) for variant prioritization. This strategy was applied to 6500 individuals including 6267 index patients and 233 NGS-based ca2025-01-01T00:00:00Z2025 Jan2025-04-22T10:23:14.458Z2025-04-05T23:35:57.883ZS-EPMC117483473983386410.1186/s12967-025-06069-2