Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation
BackgroundHereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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JMIR Publications
2020-10-01
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| Series: | Journal of Medical Internet Research |
| Online Access: | http://www.jmir.org/2020/10/e19040/ |
| _version_ | 1818405588916240384 |
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| author | Mendoza-Alvarez, Alejandro Muñoz-Barrera, Adrián Rubio-Rodríguez, Luis Alberto Marcelino-Rodriguez, Itahisa Corrales, Almudena Iñigo-Campos, Antonio Callero, Ariel Perez-Rodriguez, Eva Garcia-Robaina, Jose Carlos González-Montelongo, Rafaela Lorenzo-Salazar, Jose Miguel Flores, Carlos |
| author_facet | Mendoza-Alvarez, Alejandro Muñoz-Barrera, Adrián Rubio-Rodríguez, Luis Alberto Marcelino-Rodriguez, Itahisa Corrales, Almudena Iñigo-Campos, Antonio Callero, Ariel Perez-Rodriguez, Eva Garcia-Robaina, Jose Carlos González-Montelongo, Rafaela Lorenzo-Salazar, Jose Miguel Flores, Carlos |
| author_sort | Mendoza-Alvarez, Alejandro |
| collection | DOAJ |
| description | BackgroundHereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common.
ObjectiveIn agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing–based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA).
MethodsHADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics.
ResultsHADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools.
ConclusionsHADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay. |
| first_indexed | 2024-12-14T08:58:26Z |
| format | Article |
| id | doaj.art-5e6f91ba17ba4284980d5c7207f0a09f |
| institution | Directory Open Access Journal |
| issn | 1438-8871 |
| language | English |
| last_indexed | 2024-12-14T08:58:26Z |
| publishDate | 2020-10-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | Journal of Medical Internet Research |
| spelling | doaj.art-5e6f91ba17ba4284980d5c7207f0a09f2022-12-21T23:08:52ZengJMIR PublicationsJournal of Medical Internet Research1438-88712020-10-012210e1904010.2196/19040Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and ValidationMendoza-Alvarez, AlejandroMuñoz-Barrera, AdriánRubio-Rodríguez, Luis AlbertoMarcelino-Rodriguez, ItahisaCorrales, AlmudenaIñigo-Campos, AntonioCallero, ArielPerez-Rodriguez, EvaGarcia-Robaina, Jose CarlosGonzález-Montelongo, RafaelaLorenzo-Salazar, Jose MiguelFlores, CarlosBackgroundHereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common. ObjectiveIn agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing–based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA). MethodsHADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics. ResultsHADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools. ConclusionsHADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay.http://www.jmir.org/2020/10/e19040/ |
| spellingShingle | Mendoza-Alvarez, Alejandro Muñoz-Barrera, Adrián Rubio-Rodríguez, Luis Alberto Marcelino-Rodriguez, Itahisa Corrales, Almudena Iñigo-Campos, Antonio Callero, Ariel Perez-Rodriguez, Eva Garcia-Robaina, Jose Carlos González-Montelongo, Rafaela Lorenzo-Salazar, Jose Miguel Flores, Carlos Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation Journal of Medical Internet Research |
| title | Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation |
| title_full | Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation |
| title_fullStr | Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation |
| title_full_unstemmed | Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation |
| title_short | Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation |
| title_sort | interactive web based resource for annotation of genetic variants causing hereditary angioedema hada database development implementation and validation |
| url | http://www.jmir.org/2020/10/e19040/ |
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