ClinPrior
Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to t...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:317391 |
| Acceso en línea: | https://ddd.uab.cat/record/317391 https://dx.doi.org/urn:doi:10.1186/s13073-023-01214-2 |
| Access Level: | acceso abierto |
| Palabra clave: | Algorithm WES/WGS HPOs Variant prioritization Interactome Hereditary spastic paraplegia Cerebellar ataxia Candidate gene |
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ES_b02cc73a4335a5fd3840cd578aa72c8b |
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oai:ddd.uab.cat:317391 |
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España |
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ClinPrior an algorithm for diagnosis and novel gene discovery by network-based prioritization |
| title |
ClinPrior |
| spellingShingle |
ClinPrior Schlüter, Agatha|||0000-0001-6732-1528 Algorithm WES/WGS HPOs Variant prioritization Interactome Hereditary spastic paraplegia Cerebellar ataxia Candidate gene |
| title_short |
ClinPrior |
| title_full |
ClinPrior |
| title_fullStr |
ClinPrior |
| title_full_unstemmed |
ClinPrior |
| title_sort |
ClinPrior |
| dc.creator.none.fl_str_mv |
Schlüter, Agatha|||0000-0001-6732-1528 Vélez-Santamaría, Valentina Verdura, Edgard|||0000-0003-3856-2060 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Fourcade, Stéphane|||0000-0002-8031-5007 Planas-Serra, Laura|||0000-0002-2586-0897 Launay, Nathalie|||0000-0002-7498-217X Guilera, Cristina|||0000-0003-0715-9332 Martínez, Juan José Homedes-Pedret, Christian Albertí-Aguiló, M. Antonia Zulaika, Miren Martí, Itxaso|||0000-0003-0578-9568 Troncoso, Mónica Tomás Vila, Miguel|||0000-0002-8632-3593 Bullich Vilanova, Gemma|||0000-0002-0737-4422 García-Pérez, M. Asunción Sobrido-Gómez, María-Jesús López-Laso, Eduardo Fons, Carme Del Toro, Mireia|||0000-0002-8163-1853 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Beltran i Agulló, Sergi|||0000-0002-2810-3445 González Gutiérrez-Solana, Luis|||0000-0003-2890-4565 Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 de Munain, Adolfo López Casasnovas, Carlos|||0000-0002-7933-4681 Pujol, Aurora|||0000-0002-9606-0600 |
| author |
Schlüter, Agatha|||0000-0001-6732-1528 |
| author_facet |
Schlüter, Agatha|||0000-0001-6732-1528 Vélez-Santamaría, Valentina Verdura, Edgard|||0000-0003-3856-2060 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Fourcade, Stéphane|||0000-0002-8031-5007 Planas-Serra, Laura|||0000-0002-2586-0897 Launay, Nathalie|||0000-0002-7498-217X Guilera, Cristina|||0000-0003-0715-9332 Martínez, Juan José Homedes-Pedret, Christian Albertí-Aguiló, M. Antonia Zulaika, Miren Martí, Itxaso|||0000-0003-0578-9568 Troncoso, Mónica Tomás Vila, Miguel|||0000-0002-8632-3593 Bullich Vilanova, Gemma|||0000-0002-0737-4422 García-Pérez, M. Asunción Sobrido-Gómez, María-Jesús López-Laso, Eduardo Fons, Carme Del Toro, Mireia|||0000-0002-8163-1853 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Beltran i Agulló, Sergi|||0000-0002-2810-3445 González Gutiérrez-Solana, Luis|||0000-0003-2890-4565 Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 de Munain, Adolfo López Casasnovas, Carlos|||0000-0002-7933-4681 Pujol, Aurora|||0000-0002-9606-0600 |
| author_role |
author |
| author2 |
Vélez-Santamaría, Valentina Verdura, Edgard|||0000-0003-3856-2060 Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Fourcade, Stéphane|||0000-0002-8031-5007 Planas-Serra, Laura|||0000-0002-2586-0897 Launay, Nathalie|||0000-0002-7498-217X Guilera, Cristina|||0000-0003-0715-9332 Martínez, Juan José Homedes-Pedret, Christian Albertí-Aguiló, M. Antonia Zulaika, Miren Martí, Itxaso|||0000-0003-0578-9568 Troncoso, Mónica Tomás Vila, Miguel|||0000-0002-8632-3593 Bullich Vilanova, Gemma|||0000-0002-0737-4422 García-Pérez, M. Asunción Sobrido-Gómez, María-Jesús López-Laso, Eduardo Fons, Carme Del Toro, Mireia|||0000-0002-8163-1853 Macaya Ruiz, Alfons|||0000-0001-7998-4185 Beltran i Agulló, Sergi|||0000-0002-2810-3445 González Gutiérrez-Solana, Luis|||0000-0003-2890-4565 Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 de Munain, Adolfo López Casasnovas, Carlos|||0000-0002-7933-4681 Pujol, Aurora|||0000-0002-9606-0600 |
| 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 |
| dc.subject.none.fl_str_mv |
Algorithm WES/WGS HPOs Variant prioritization Interactome Hereditary spastic paraplegia Cerebellar ataxia Candidate gene |
| topic |
Algorithm WES/WGS HPOs Variant prioritization Interactome Hereditary spastic paraplegia Cerebellar ataxia Candidate gene |
| description |
Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses. The online version contains supplementary material available at 10.1186/s13073-023-01214-2. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2 2023-01-01 2023 2023-01-01 |
| 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/317391 https://dx.doi.org/urn:doi:10.1186/s13073-023-01214-2 |
| url |
https://ddd.uab.cat/record/317391 https://dx.doi.org/urn:doi:10.1186/s13073-023-01214-2 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Generalitat de Catalunya https://doi.org/10.13039/501100002809 SLT002/16/00174 Fundació la Marató de TV3 https://doi.org/10.13039/100008666 202006-30 Fundació la Marató de TV3 https://doi.org/10.13039/100008666 504/C/2020 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CPII16/00016 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
| dc.source.none.fl_str_mv |
reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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1869416785232527360 |
| spelling |
ClinPrioran algorithm for diagnosis and novel gene discovery by network-based prioritizationSchlüter, Agatha|||0000-0001-6732-1528Vélez-Santamaría, ValentinaVerdura, Edgard|||0000-0003-3856-2060Rodríguez-Palmero, Agustí|||0000-0002-4141-5515Ruiz, Montserrat|||0000-0003-0466-2653Fourcade, Stéphane|||0000-0002-8031-5007Planas-Serra, Laura|||0000-0002-2586-0897Launay, Nathalie|||0000-0002-7498-217XGuilera, Cristina|||0000-0003-0715-9332Martínez, Juan JoséHomedes-Pedret, ChristianAlbertí-Aguiló, M. AntoniaZulaika, MirenMartí, Itxaso|||0000-0003-0578-9568Troncoso, MónicaTomás Vila, Miguel|||0000-0002-8632-3593Bullich Vilanova, Gemma|||0000-0002-0737-4422García-Pérez, M. AsunciónSobrido-Gómez, María-JesúsLópez-Laso, EduardoFons, CarmeDel Toro, Mireia|||0000-0002-8163-1853Macaya Ruiz, Alfons|||0000-0001-7998-4185Beltran i Agulló, Sergi|||0000-0002-2810-3445González Gutiérrez-Solana, Luis|||0000-0003-2890-4565Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005Aguilera-Albesa, Sergio|||0000-0003-3540-1448de Munain, Adolfo LópezCasasnovas, Carlos|||0000-0002-7933-4681Pujol, Aurora|||0000-0002-9606-0600AlgorithmWES/WGSHPOsVariant prioritizationInteractomeHereditary spastic paraplegiaCerebellar ataxiaCandidate geneWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses. The online version contains supplementary material available at 10.1186/s13073-023-01214-2. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/317391https://dx.doi.org/urn:doi:10.1186/s13073-023-01214-2reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengGeneralitat de Catalunya https://doi.org/10.13039/501100002809 SLT002/16/00174Fundació la Marató de TV3 https://doi.org/10.13039/100008666 202006-30Fundació la Marató de TV3 https://doi.org/10.13039/100008666 504/C/2020Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CPII16/00016open 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, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3173912026-06-06T12:50:31Z |
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15.812429 |