Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases
Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpreta...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:277657 |
| Acceso en línea: | https://ddd.uab.cat/record/277657 https://dx.doi.org/urn:doi:10.1016/j.jmoldx.2022.02.003 |
| Access Level: | acceso abierto |
| Palabra clave: | Computational Biology Exome Genomics Humans Rare Diseases Whole Exome Sequencing |
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oai:ddd.uab.cat:277657 |
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| dc.title.none.fl_str_mv |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| title |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| spellingShingle |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases Bullich Vilanova, Gemma|||0000-0002-0737-4422 Computational Biology Exome Genomics Humans Rare Diseases Whole Exome Sequencing |
| title_short |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| title_full |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| title_fullStr |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| title_full_unstemmed |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| title_sort |
Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases |
| dc.creator.none.fl_str_mv |
Bullich Vilanova, Gemma|||0000-0002-0737-4422 Matalonga, Leslie Pujadas, Montserrat Papakonstantinou, Anastasios Piscia, Davide Tonda, Raúl Artuch, R.|||0000-0002-3422-9685 Gallano, Pia|||0000-0001-8104-2197 Garrabou, Glòria|||0000-0001-8973-9933 González, Juan Ramón|||0000-0003-3267-2146 Grinberg, Daniel|||0000-0001-9859-2590 Guitart, Maria|||0000-0003-2957-7404 Laurie, Steven|||0000-0003-3913-5829 Lázaro García, Conxi|||0000-0002-7198-5906 Luengo, Cristina Martí, Ramon A.|||0000-0002-8273-9540 Milà, Montserrat Ovelleiro, David|||0000-0002-9415-2229 Parra, Genís Pujol, Aurora|||0000-0002-9606-0600 Tizzano, Eduardo F.|||0000-0002-7116-6310 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Palau, Francesc|||0000-0002-8635-5421 Ribes, Antònia Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Beltran i Agulló, Sergi|||0000-0002-2810-3445 Schlüter, Agatha|||0000-0001-6732-1528 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Cáceres, Alejandro|||0000-0001-8551-6695 Nascimento, Andrés García-Cazorla, Àngels Cueto-González, Anna Mª|||0000-0001-7694-6124 Marcé-Grau, Anna|||0000-0001-5762-4023 Ruiz Nel Lo, Anna Martínez-Monseny, Antonio Sánchez, Aurora|||0000-0003-1167-1451 García, Belén Pérez-Dueñas, Belén|||0000-0002-4979-2788 Gel, Bernat|||0000-0001-8878-349X Fusté, Berta Hernández-Ferrer, Carles Casasnovas, Carlos|||0000-0002-7933-4681 Ortez González, Carlos Ignacio|||0000-0001-8187-8103 Arjona, César Hernando Davalillo, Cristina Natera de Benito, Daniel Picó Amador, Daniel Gómez-Andrés, David|||0000-0001-5654-7791 Yubero, Délia Pelegrí-Sisó, Dolors|||0000-0002-5993-3003 Verdura, Edgard|||0000-0003-3856-2060 García Arumí, Elena|||0000-0003-1848-005X Castellanos, Elisabeth|||0000-0002-8133-5325 Gabau, Elisabeth|||0000-0001-8120-7393 Tobías, Ester|||0000-0002-9968-3651 López-Grondona, Fermina Cardellach, Francesc|||0000-0003-3286-3436 Garcia-Garcia, Francesc Josep Munell Casadesus, Francina|||0000-0001-8580-2819 Tort, Frederic|||0000-0003-2733-1603 Aznar, Gemma Olive Cirera, Gemma Tell-Martí, Gemma|||0000-0003-2728-6961 Muñoz-Pujol, Gerard|||0000-0002-6863-3993 Paramonov, Ida Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Madrigal, Irene|||0000-0002-7229-1199 Valenzuela, Irene|||0000-0003-2350-6058 Gut, Ivo|||0000-0001-7219-632X Cusco, Ivon|||0000-0003-2104-9332 Trotta, Jean-Rémi Cruz, Jordi Diaz-Manera, Jordi|||0000-0003-2941-7988 Milisenda, José César|||0000-0003-0151-7872 Ma Grau, Josep Garcia-Villoria, Judit Armstrong, Judith|||0000-0003-0588-9307 Cantó, Judith Sala-Coromina, Júlia|||0000-0001-5116-6316 Rodríguez-Revenga, Laia Alías, Laura|||0000-0003-2193-6185 Gort, Laura|||0000-0003-4746-1034 González Quereda, Lidia|||0000-0003-0715-6414 Costa, Mar Fernández-Callejo, Marcos López Sánchez, Marcos|||0000-0002-1517-5968 Álvarez Mora, María Isabel|||0000-0003-3788-8915 Gut, Marta|||0000-0002-4063-7159 Serrano, Mercedes|||0000-0002-2056-2428 Raspall-Chaure, Miquel|||0000-0002-3132-3342 Del Toro, Mireia|||0000-0002-8163-1853 Bayés, Mònica Baena Díez, Neus|||0000-0003-0677-240X Spataro, Nino|||0000-0002-2127-2238 Capdevila, Núria|||0000-0003-2080-7381 Ugarteburu, Olatz|||0000-0003-4214-3301 Muñoz-Cabello, Patricia|||0000-0002-5242-9605 Romero Duque, Penélope|||0000-0003-3509-1320 Rabionet, Raquel|||0000-0001-5006-8140 Rojas-Garcia, Ricard|||0000-0003-1411-5573 Calvo-Escalona, Rosa|||0000-0001-9572-4228 Urreizti, Roser|||0000-0003-3617-7134 Bernal, Sara|||0000-0003-4427-0574 Boronat, Susana|||0000-0001-7096-5578 Balcells, Susana|||0000-0003-1211-1907 Vendrell, Teresa |
| author |
Bullich Vilanova, Gemma|||0000-0002-0737-4422 |
| author_facet |
Bullich Vilanova, Gemma|||0000-0002-0737-4422 Matalonga, Leslie Pujadas, Montserrat Papakonstantinou, Anastasios Piscia, Davide Tonda, Raúl Artuch, R.|||0000-0002-3422-9685 Gallano, Pia|||0000-0001-8104-2197 Garrabou, Glòria|||0000-0001-8973-9933 González, Juan Ramón|||0000-0003-3267-2146 Grinberg, Daniel|||0000-0001-9859-2590 Guitart, Maria|||0000-0003-2957-7404 Laurie, Steven|||0000-0003-3913-5829 Lázaro García, Conxi|||0000-0002-7198-5906 Luengo, Cristina Martí, Ramon A.|||0000-0002-8273-9540 Milà, Montserrat Ovelleiro, David|||0000-0002-9415-2229 Parra, Genís Pujol, Aurora|||0000-0002-9606-0600 Tizzano, Eduardo F.|||0000-0002-7116-6310 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Palau, Francesc|||0000-0002-8635-5421 Ribes, Antònia Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Beltran i Agulló, Sergi|||0000-0002-2810-3445 Schlüter, Agatha|||0000-0001-6732-1528 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Cáceres, Alejandro|||0000-0001-8551-6695 Nascimento, Andrés García-Cazorla, Àngels Cueto-González, Anna Mª|||0000-0001-7694-6124 Marcé-Grau, Anna|||0000-0001-5762-4023 Ruiz Nel Lo, Anna Martínez-Monseny, Antonio Sánchez, Aurora|||0000-0003-1167-1451 García, Belén Pérez-Dueñas, Belén|||0000-0002-4979-2788 Gel, Bernat|||0000-0001-8878-349X Fusté, Berta Hernández-Ferrer, Carles Casasnovas, Carlos|||0000-0002-7933-4681 Ortez González, Carlos Ignacio|||0000-0001-8187-8103 Arjona, César Hernando Davalillo, Cristina Natera de Benito, Daniel Picó Amador, Daniel Gómez-Andrés, David|||0000-0001-5654-7791 Yubero, Délia Pelegrí-Sisó, Dolors|||0000-0002-5993-3003 Verdura, Edgard|||0000-0003-3856-2060 García Arumí, Elena|||0000-0003-1848-005X Castellanos, Elisabeth|||0000-0002-8133-5325 Gabau, Elisabeth|||0000-0001-8120-7393 Tobías, Ester|||0000-0002-9968-3651 López-Grondona, Fermina Cardellach, Francesc|||0000-0003-3286-3436 Garcia-Garcia, Francesc Josep Munell Casadesus, Francina|||0000-0001-8580-2819 Tort, Frederic|||0000-0003-2733-1603 Aznar, Gemma Olive Cirera, Gemma Tell-Martí, Gemma|||0000-0003-2728-6961 Muñoz-Pujol, Gerard|||0000-0002-6863-3993 Paramonov, Ida Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Madrigal, Irene|||0000-0002-7229-1199 Valenzuela, Irene|||0000-0003-2350-6058 Gut, Ivo|||0000-0001-7219-632X Cusco, Ivon|||0000-0003-2104-9332 Trotta, Jean-Rémi Cruz, Jordi Diaz-Manera, Jordi|||0000-0003-2941-7988 Milisenda, José César|||0000-0003-0151-7872 Ma Grau, Josep Garcia-Villoria, Judit Armstrong, Judith|||0000-0003-0588-9307 Cantó, Judith Sala-Coromina, Júlia|||0000-0001-5116-6316 Rodríguez-Revenga, Laia Alías, Laura|||0000-0003-2193-6185 Gort, Laura|||0000-0003-4746-1034 González Quereda, Lidia|||0000-0003-0715-6414 Costa, Mar Fernández-Callejo, Marcos López Sánchez, Marcos|||0000-0002-1517-5968 Álvarez Mora, María Isabel|||0000-0003-3788-8915 Gut, Marta|||0000-0002-4063-7159 Serrano, Mercedes|||0000-0002-2056-2428 Raspall-Chaure, Miquel|||0000-0002-3132-3342 Del Toro, Mireia|||0000-0002-8163-1853 Bayés, Mònica Baena Díez, Neus|||0000-0003-0677-240X Spataro, Nino|||0000-0002-2127-2238 Capdevila, Núria|||0000-0003-2080-7381 Ugarteburu, Olatz|||0000-0003-4214-3301 Muñoz-Cabello, Patricia|||0000-0002-5242-9605 Romero Duque, Penélope|||0000-0003-3509-1320 Rabionet, Raquel|||0000-0001-5006-8140 Rojas-Garcia, Ricard|||0000-0003-1411-5573 Calvo-Escalona, Rosa|||0000-0001-9572-4228 Urreizti, Roser|||0000-0003-3617-7134 Bernal, Sara|||0000-0003-4427-0574 Boronat, Susana|||0000-0001-7096-5578 Balcells, Susana|||0000-0003-1211-1907 Vendrell, Teresa |
| author_role |
author |
| author2 |
Matalonga, Leslie Pujadas, Montserrat Papakonstantinou, Anastasios Piscia, Davide Tonda, Raúl Artuch, R.|||0000-0002-3422-9685 Gallano, Pia|||0000-0001-8104-2197 Garrabou, Glòria|||0000-0001-8973-9933 González, Juan Ramón|||0000-0003-3267-2146 Grinberg, Daniel|||0000-0001-9859-2590 Guitart, Maria|||0000-0003-2957-7404 Laurie, Steven|||0000-0003-3913-5829 Lázaro García, Conxi|||0000-0002-7198-5906 Luengo, Cristina Martí, Ramon A.|||0000-0002-8273-9540 Milà, Montserrat Ovelleiro, David|||0000-0002-9415-2229 Parra, Genís Pujol, Aurora|||0000-0002-9606-0600 Tizzano, Eduardo F.|||0000-0002-7116-6310 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Palau, Francesc|||0000-0002-8635-5421 Ribes, Antònia Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Beltran i Agulló, Sergi|||0000-0002-2810-3445 Schlüter, Agatha|||0000-0001-6732-1528 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Cáceres, Alejandro|||0000-0001-8551-6695 Nascimento, Andrés García-Cazorla, Àngels Cueto-González, Anna Mª|||0000-0001-7694-6124 Marcé-Grau, Anna|||0000-0001-5762-4023 Ruiz Nel Lo, Anna Martínez-Monseny, Antonio Sánchez, Aurora|||0000-0003-1167-1451 García, Belén Pérez-Dueñas, Belén|||0000-0002-4979-2788 Gel, Bernat|||0000-0001-8878-349X Fusté, Berta Hernández-Ferrer, Carles Casasnovas, Carlos|||0000-0002-7933-4681 Ortez González, Carlos Ignacio|||0000-0001-8187-8103 Arjona, César Hernando Davalillo, Cristina Natera de Benito, Daniel Picó Amador, Daniel Gómez-Andrés, David|||0000-0001-5654-7791 Yubero, Délia Pelegrí-Sisó, Dolors|||0000-0002-5993-3003 Verdura, Edgard|||0000-0003-3856-2060 García Arumí, Elena|||0000-0003-1848-005X Castellanos, Elisabeth|||0000-0002-8133-5325 Gabau, Elisabeth|||0000-0001-8120-7393 Tobías, Ester|||0000-0002-9968-3651 López-Grondona, Fermina Cardellach, Francesc|||0000-0003-3286-3436 Garcia-Garcia, Francesc Josep Munell Casadesus, Francina|||0000-0001-8580-2819 Tort, Frederic|||0000-0003-2733-1603 Aznar, Gemma Olive Cirera, Gemma Tell-Martí, Gemma|||0000-0003-2728-6961 Muñoz-Pujol, Gerard|||0000-0002-6863-3993 Paramonov, Ida Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Madrigal, Irene|||0000-0002-7229-1199 Valenzuela, Irene|||0000-0003-2350-6058 Gut, Ivo|||0000-0001-7219-632X Cusco, Ivon|||0000-0003-2104-9332 Trotta, Jean-Rémi Cruz, Jordi Diaz-Manera, Jordi|||0000-0003-2941-7988 Milisenda, José César|||0000-0003-0151-7872 Ma Grau, Josep Garcia-Villoria, Judit Armstrong, Judith|||0000-0003-0588-9307 Cantó, Judith Sala-Coromina, Júlia|||0000-0001-5116-6316 Rodríguez-Revenga, Laia Alías, Laura|||0000-0003-2193-6185 Gort, Laura|||0000-0003-4746-1034 González Quereda, Lidia|||0000-0003-0715-6414 Costa, Mar Fernández-Callejo, Marcos López Sánchez, Marcos|||0000-0002-1517-5968 Álvarez Mora, María Isabel|||0000-0003-3788-8915 Gut, Marta|||0000-0002-4063-7159 Serrano, Mercedes|||0000-0002-2056-2428 Raspall-Chaure, Miquel|||0000-0002-3132-3342 Del Toro, Mireia|||0000-0002-8163-1853 Bayés, Mònica Baena Díez, Neus|||0000-0003-0677-240X Spataro, Nino|||0000-0002-2127-2238 Capdevila, Núria|||0000-0003-2080-7381 Ugarteburu, Olatz|||0000-0003-4214-3301 Muñoz-Cabello, Patricia|||0000-0002-5242-9605 Romero Duque, Penélope|||0000-0003-3509-1320 Rabionet, Raquel|||0000-0001-5006-8140 Rojas-Garcia, Ricard|||0000-0003-1411-5573 Calvo-Escalona, Rosa|||0000-0001-9572-4228 Urreizti, Roser|||0000-0003-3617-7134 Bernal, Sara|||0000-0003-4427-0574 Boronat, Susana|||0000-0001-7096-5578 Balcells, Susana|||0000-0003-1211-1907 Vendrell, Teresa |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Computational Biology Exome Genomics Humans Rare Diseases Whole Exome Sequencing |
| topic |
Computational Biology Exome Genomics Humans Rare Diseases Whole Exome Sequencing |
| description |
Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/277657 https://dx.doi.org/urn:doi:10.1016/j.jmoldx.2022.02.003 |
| url |
https://ddd.uab.cat/record/277657 https://dx.doi.org/urn:doi:10.1016/j.jmoldx.2022.02.003 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
European Commission https://doi.org/10.13039/501100000780 305444 European Commission https://doi.org/10.13039/501100000780 779257 European Commission https://doi.org/10.13039/501100000780 825575 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 SLT002/16/00174 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PT13/0001/0044 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT17/0009/0019 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01048 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/01310 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00451 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00498 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00935 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SEV-2016-0571 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 CEX2018-000806-S |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
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Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare DiseasesBullich Vilanova, Gemma|||0000-0002-0737-4422Matalonga, LesliePujadas, MontserratPapakonstantinou, AnastasiosPiscia, DavideTonda, RaúlArtuch, R.|||0000-0002-3422-9685Gallano, Pia|||0000-0001-8104-2197Garrabou, Glòria|||0000-0001-8973-9933González, Juan Ramón|||0000-0003-3267-2146Grinberg, Daniel|||0000-0001-9859-2590Guitart, Maria|||0000-0003-2957-7404Laurie, Steven|||0000-0003-3913-5829Lázaro García, Conxi|||0000-0002-7198-5906Luengo, CristinaMartí, Ramon A.|||0000-0002-8273-9540Milà, MontserratOvelleiro, David|||0000-0002-9415-2229Parra, GenísPujol, Aurora|||0000-0002-9606-0600Tizzano, Eduardo F.|||0000-0002-7116-6310Macaya Ruiz, Alfons|||0000-0001-7998-4185Palau, Francesc|||0000-0002-8635-5421Ribes, AntòniaPérez-Jurado, Luis Alberto|||0000-0002-1988-3005Beltran i Agulló, Sergi|||0000-0002-2810-3445Schlüter, Agatha|||0000-0001-6732-1528Rodríguez-Palmero, Agustí|||0000-0002-4141-5515Cáceres, Alejandro|||0000-0001-8551-6695Nascimento, AndrésGarcía-Cazorla, ÀngelsCueto-González, Anna Mª|||0000-0001-7694-6124Marcé-Grau, Anna|||0000-0001-5762-4023Ruiz Nel Lo, AnnaMartínez-Monseny, AntonioSánchez, Aurora|||0000-0003-1167-1451García, BelénPérez-Dueñas, Belén|||0000-0002-4979-2788Gel, Bernat|||0000-0001-8878-349XFusté, BertaHernández-Ferrer, CarlesCasasnovas, Carlos|||0000-0002-7933-4681Ortez González, Carlos Ignacio|||0000-0001-8187-8103Arjona, CésarHernando Davalillo, CristinaNatera de Benito, DanielPicó Amador, DanielGómez-Andrés, David|||0000-0001-5654-7791Yubero, DéliaPelegrí-Sisó, Dolors|||0000-0002-5993-3003Verdura, Edgard|||0000-0003-3856-2060García Arumí, Elena|||0000-0003-1848-005XCastellanos, Elisabeth|||0000-0002-8133-5325Gabau, Elisabeth|||0000-0001-8120-7393Tobías, Ester|||0000-0002-9968-3651López-Grondona, FerminaCardellach, Francesc|||0000-0003-3286-3436Garcia-Garcia, Francesc JosepMunell Casadesus, Francina|||0000-0001-8580-2819Tort, Frederic|||0000-0003-2733-1603Aznar, GemmaOlive Cirera, GemmaTell-Martí, Gemma|||0000-0003-2728-6961Muñoz-Pujol, Gerard|||0000-0002-6863-3993Paramonov, IdaBlanco Guillermo, Ignacio|||0000-0002-7414-7481Madrigal, Irene|||0000-0002-7229-1199Valenzuela, Irene|||0000-0003-2350-6058Gut, Ivo|||0000-0001-7219-632XCusco, Ivon|||0000-0003-2104-9332Trotta, Jean-RémiCruz, JordiDiaz-Manera, Jordi|||0000-0003-2941-7988Milisenda, José César|||0000-0003-0151-7872Ma Grau, JosepGarcia-Villoria, JuditArmstrong, Judith|||0000-0003-0588-9307Cantó, JudithSala-Coromina, Júlia|||0000-0001-5116-6316Rodríguez-Revenga, LaiaAlías, Laura|||0000-0003-2193-6185Gort, Laura|||0000-0003-4746-1034González Quereda, Lidia|||0000-0003-0715-6414Costa, MarFernández-Callejo, MarcosLópez Sánchez, Marcos|||0000-0002-1517-5968Álvarez Mora, María Isabel|||0000-0003-3788-8915Gut, Marta|||0000-0002-4063-7159Serrano, Mercedes|||0000-0002-2056-2428Raspall-Chaure, Miquel|||0000-0002-3132-3342Del Toro, Mireia|||0000-0002-8163-1853Bayés, MònicaBaena Díez, Neus|||0000-0003-0677-240XSpataro, Nino|||0000-0002-2127-2238Capdevila, Núria|||0000-0003-2080-7381Ugarteburu, Olatz|||0000-0003-4214-3301Muñoz-Cabello, Patricia|||0000-0002-5242-9605Romero Duque, Penélope|||0000-0003-3509-1320Rabionet, Raquel|||0000-0001-5006-8140Rojas-Garcia, Ricard|||0000-0003-1411-5573Calvo-Escalona, Rosa|||0000-0001-9572-4228Urreizti, Roser|||0000-0003-3617-7134Bernal, Sara|||0000-0003-4427-0574Boronat, Susana|||0000-0001-7096-5578Balcells, Susana|||0000-0003-1211-1907Vendrell, TeresaComputational BiologyExomeGenomicsHumansRare DiseasesWhole Exome SequencingMany patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%).Universitat Autònoma de Barcelona 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/277657https://dx.doi.org/urn:doi:10.1016/j.jmoldx.2022.02.003reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 305444European Commission https://doi.org/10.13039/501100000780 779257European Commission https://doi.org/10.13039/501100000780 825575Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 SLT002/16/00174Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PT13/0001/0044Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT17/0009/0019Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01048Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/01310Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00451Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00498Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00935Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SEV-2016-0571Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 CEX2018-000806-Sopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2776572026-06-06T12:50:31Z |
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