A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice
Abstract Background 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 clinica...
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06069-2 |
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| author | Cristina Méndez-Vidal Nereida Bravo-Gil Javier Pérez-Florido Irene Marcos-Luque Raquel M. Fernández José Luis Fernández-Rueda María González-del Pozo Marta Martín-Sánchez Elena Fernández-Suárez Marcela Mena Rosario Carmona Joaquín Dopazo Salud Borrego Guillermo Antiñolo |
| author_facet | Cristina Méndez-Vidal Nereida Bravo-Gil Javier Pérez-Florido Irene Marcos-Luque Raquel M. Fernández José Luis Fernández-Rueda María González-del Pozo Marta Martín-Sánchez Elena Fernández-Suárez Marcela Mena Rosario Carmona Joaquín Dopazo Salud Borrego Guillermo Antiñolo |
| author_sort | Cristina Méndez-Vidal |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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 carrier screenings. Results Causative variants were identified in 2061 index patients (average 32.9%, ranging from 12 to 62% by condition). Also, 131 autosomal-recessive cases could be partially genetically diagnosed. These results led to over 5000 additional studies including carrier, prenatal and preimplantational tests or pharmacological and gene therapy treatments. Conclusion This strategy has shown promising improvements in the diagnostic rate, facilitating timely diagnosis and gradually expanding our services portfolio for rare diseases. The steps taken towards the integration of clinical and genomic data are opening new possibilities for conducting both retrospective and prospective healthcare studies. Overall, this study represents a major milestone in the ongoing efforts to improve our understanding and clinical management of rare diseases, a crucial area of medical research and care. |
| format | Article |
| id | doaj-art-1fc059a5457b4ce1b024f0d76c9adc7c |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-1fc059a5457b4ce1b024f0d76c9adc7c2025-01-26T12:50:15ZengBMCJournal of Translational Medicine1479-58762025-01-0123111510.1186/s12967-025-06069-2A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practiceCristina Méndez-Vidal0Nereida Bravo-Gil1Javier Pérez-Florido2Irene Marcos-Luque3Raquel M. Fernández4José Luis Fernández-Rueda5María González-del Pozo6Marta Martín-Sánchez7Elena Fernández-Suárez8Marcela Mena9Rosario Carmona10Joaquín Dopazo11Salud Borrego12Guillermo Antiñolo13Institute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleCentre for Biomedical Network Research on Rare Diseases (CIBERER)Centre for Biomedical Network Research on Rare Diseases (CIBERER)Platform of Computational Medicine. Fundación Progreso y Salud (FPS). CDCA, University Hospital Virgen del RocioInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleInstitute of Biomedicine of Seville, IBiS/University Hospital Virgen del Rocio, CSIC/University of SevilleCentre for Biomedical Network Research on Rare Diseases (CIBERER)Centre for Biomedical Network Research on Rare Diseases (CIBERER)Abstract Background 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. Methods 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 carrier screenings. Results Causative variants were identified in 2061 index patients (average 32.9%, ranging from 12 to 62% by condition). Also, 131 autosomal-recessive cases could be partially genetically diagnosed. These results led to over 5000 additional studies including carrier, prenatal and preimplantational tests or pharmacological and gene therapy treatments. Conclusion This strategy has shown promising improvements in the diagnostic rate, facilitating timely diagnosis and gradually expanding our services portfolio for rare diseases. The steps taken towards the integration of clinical and genomic data are opening new possibilities for conducting both retrospective and prospective healthcare studies. Overall, this study represents a major milestone in the ongoing efforts to improve our understanding and clinical management of rare diseases, a crucial area of medical research and care.https://doi.org/10.1186/s12967-025-06069-2Rare diseasesGenetic diagnosisNext generation sequencingPrecision medicineResearch implementationGenomic medicine |
| spellingShingle | Cristina Méndez-Vidal Nereida Bravo-Gil Javier Pérez-Florido Irene Marcos-Luque Raquel M. Fernández José Luis Fernández-Rueda María González-del Pozo Marta Martín-Sánchez Elena Fernández-Suárez Marcela Mena Rosario Carmona Joaquín Dopazo Salud Borrego Guillermo Antiñolo A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice Journal of Translational Medicine Rare diseases Genetic diagnosis Next generation sequencing Precision medicine Research implementation Genomic medicine |
| title | A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice |
| title_full | A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice |
| title_fullStr | A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice |
| title_full_unstemmed | A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice |
| title_short | A genomic strategy for precision medicine in rare diseases: integrating customized algorithms into clinical practice |
| title_sort | genomic strategy for precision medicine in rare diseases integrating customized algorithms into clinical practice |
| topic | Rare diseases Genetic diagnosis Next generation sequencing Precision medicine Research implementation Genomic medicine |
| url | https://doi.org/10.1186/s12967-025-06069-2 |
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