Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis
Introduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories.Pat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1122985/full |
| _version_ | 1827964048545677312 |
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| author | Frédéric Tran Mau-Them Frédéric Tran Mau-Them Alexis Overs Ange-Line Bruel Ange-Line Bruel Romain Duquet Mylene Thareau Anne-Sophie Denommé-Pichon Anne-Sophie Denommé-Pichon Antonio Vitobello Antonio Vitobello Arthur Sorlin Arthur Sorlin Hana Safraou Hana Safraou Sophie Nambot Julian Delanne Sebastien Moutton Caroline Racine Camille Engel Melchior De Giraud d’Agay Daphne Lehalle Alice Goldenberg Alice Goldenberg Marjolaine Willems Christine Coubes David Genevieve Alain Verloes Alain Verloes Yline Capri Laurence Perrin Marie-Line Jacquemont Laetitia Lambert Elodie Lacaze Julien Thevenon Nadine Hana Nadine Hana Julien Van-Gils Charlotte Dubucs Varoona Bizaoui Marion Gerard-Blanluet James Lespinasse Sandra Mercier Anne-Marie Guerrot Anne-Marie Guerrot Isabelle Maystadt Emilie Tisserant Laurence Faivre Laurence Faivre Christophe Philippe Christophe Philippe Yannis Duffourd Yannis Duffourd Christel Thauvin-Robinet Christel Thauvin-Robinet Christel Thauvin-Robinet |
| author_facet | Frédéric Tran Mau-Them Frédéric Tran Mau-Them Alexis Overs Ange-Line Bruel Ange-Line Bruel Romain Duquet Mylene Thareau Anne-Sophie Denommé-Pichon Anne-Sophie Denommé-Pichon Antonio Vitobello Antonio Vitobello Arthur Sorlin Arthur Sorlin Hana Safraou Hana Safraou Sophie Nambot Julian Delanne Sebastien Moutton Caroline Racine Camille Engel Melchior De Giraud d’Agay Daphne Lehalle Alice Goldenberg Alice Goldenberg Marjolaine Willems Christine Coubes David Genevieve Alain Verloes Alain Verloes Yline Capri Laurence Perrin Marie-Line Jacquemont Laetitia Lambert Elodie Lacaze Julien Thevenon Nadine Hana Nadine Hana Julien Van-Gils Charlotte Dubucs Varoona Bizaoui Marion Gerard-Blanluet James Lespinasse Sandra Mercier Anne-Marie Guerrot Anne-Marie Guerrot Isabelle Maystadt Emilie Tisserant Laurence Faivre Laurence Faivre Christophe Philippe Christophe Philippe Yannis Duffourd Yannis Duffourd Christel Thauvin-Robinet Christel Thauvin-Robinet Christel Thauvin-Robinet |
| author_sort | Frédéric Tran Mau-Them |
| collection | DOAJ |
| description | Introduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories.Patients and methods: We applied a reanalysis strategy based on intensive prospective bibliographic monitoring along with direct application of the GREP command-line tool (to “globally search for a regular expression and print matching lines”) in a large ES database. For 18 months, we submitted the same five keywords of interest [(intellectual disability, (neuro)developmental delay, and (neuro)developmental disorder)] to PubMed on a daily basis to identify recently published novel disease–gene associations or new phenotypes in genes already implicated in human pathology. We used the Linux GREP tool and an in-house script to collect all variants of these genes from our 5,459 exome database.Results: After GREP queries and variant filtration, we identified 128 genes of interest and collected 56 candidate variants from 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, GREP queries for only 128 genes over a period of 18 months permitted a causal diagnosis to be established in 21/2875 undiagnosed affected probands (0.7%).Conclusion: The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis. |
| first_indexed | 2024-04-09T17:09:02Z |
| format | Article |
| id | doaj.art-c14e4795329344a3bad7a62c2a7011bd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T17:09:02Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-c14e4795329344a3bad7a62c2a7011bd2023-04-20T09:03:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-04-011410.3389/fgene.2023.11229851122985Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosisFrédéric Tran Mau-Them0Frédéric Tran Mau-Them1Alexis Overs2Ange-Line Bruel3Ange-Line Bruel4Romain Duquet5Mylene Thareau6Anne-Sophie Denommé-Pichon7Anne-Sophie Denommé-Pichon8Antonio Vitobello9Antonio Vitobello10Arthur Sorlin11Arthur Sorlin12Hana Safraou13Hana Safraou14Sophie Nambot15Julian Delanne16Sebastien Moutton17Caroline Racine18Camille Engel19Melchior De Giraud d’Agay20Daphne Lehalle21Alice Goldenberg22Alice Goldenberg23Marjolaine Willems24Christine Coubes25David Genevieve26Alain Verloes27Alain Verloes28Yline Capri29Laurence Perrin30Marie-Line Jacquemont31Laetitia Lambert32Elodie Lacaze33Julien Thevenon34Nadine Hana35Nadine Hana36Julien Van-Gils37Charlotte Dubucs38Varoona Bizaoui39Marion Gerard-Blanluet40James Lespinasse41Sandra Mercier42Anne-Marie Guerrot43Anne-Marie Guerrot44Isabelle Maystadt45Emilie Tisserant46Laurence Faivre47Laurence Faivre48Christophe Philippe49Christophe Philippe50Yannis Duffourd51Yannis Duffourd52Christel Thauvin-Robinet53Christel Thauvin-Robinet54Christel Thauvin-Robinet55Unité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceNormandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, FranceDepartment of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Rouen, FranceDépartement de Génétique Médicale Maladies Rares et Médecine Personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, FranceDépartement de Génétique Médicale Maladies Rares et Médecine Personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, FranceDépartement de Génétique Médicale Maladies Rares et Médecine Personnalisée, Centre de Référence Maladies Rares Anomalies du Développement, Hôpital Arnaud de Villeneuve, Université Montpellier, Montpellier, FranceCentre de Référence Anomalies du Développement et Syndromes Malformatifs, Department of Medical Genetics, AP-HPNord- Université de Paris, Hôpital Robert Debré, Paris, FranceINSERM UMR 1141, Paris, FranceService de Génétique Clinique, CHU Robert Debré, Paris, FranceService de Génétique Clinique, CHU Robert Debré, Paris, France0Unité de Génétique Médicale, Pole Femme-Mère-Enfant, Groupe Hospitalier Sud Réunion, CHU de La Réunion, La Réunion, France1Service de Génétique Clinique, CHRU Nancy, Paris, France2Unité de Génétique Médicale, Groupe Hospitalier du Havre, Le Havre, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, France3Département de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France4INSERM U1148, Laboratory for Vascular Translational Science, Université Paris de Paris, Hôpital Bichat, Paris, France5Service de Génétique Médicale, CHU de Bordeaux, Bordeaux, France6Department of Medical Genetics, Toulouse University Hospital, Toulouse, France7Service de Génétique, Centre Hospitalier Universitaire Caen Normandie, Caen, France7Service de Génétique, Centre Hospitalier Universitaire Caen Normandie, Caen, France8Service de Génétique clinique, CH de Chambéry, Chambéry, France9Service de Génétique Médicale, CHU Nantes, Nantes, France0Department of Genetics and Reference Center for Developmental Disorders, Normandie Univ, UNIROUEN, CHU Rouen, Rouen, France1Inserm U1245, FHU G4 Génomique, Rouen, France2Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, BelgiumUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceUnité Fonctionnelle Innovation en Diagnostic Génomique des maladies rares, CHU Dijon, Dijon, FranceINSERM UMR1231 GAD, Dijon, FranceCentre de Référence Maladies Rares “Anomalies du développement et syndromes malformatifs”, Centre de Génétique, FHUTRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, FranceIntroduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories.Patients and methods: We applied a reanalysis strategy based on intensive prospective bibliographic monitoring along with direct application of the GREP command-line tool (to “globally search for a regular expression and print matching lines”) in a large ES database. For 18 months, we submitted the same five keywords of interest [(intellectual disability, (neuro)developmental delay, and (neuro)developmental disorder)] to PubMed on a daily basis to identify recently published novel disease–gene associations or new phenotypes in genes already implicated in human pathology. We used the Linux GREP tool and an in-house script to collect all variants of these genes from our 5,459 exome database.Results: After GREP queries and variant filtration, we identified 128 genes of interest and collected 56 candidate variants from 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, GREP queries for only 128 genes over a period of 18 months permitted a causal diagnosis to be established in 21/2875 undiagnosed affected probands (0.7%).Conclusion: The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis.https://www.frontiersin.org/articles/10.3389/fgene.2023.1122985/fullGREPintellectual disabilitydevelopmental anomaliesgenomic databasediagnostic improvementexome sequencing (ES) |
| spellingShingle | Frédéric Tran Mau-Them Frédéric Tran Mau-Them Alexis Overs Ange-Line Bruel Ange-Line Bruel Romain Duquet Mylene Thareau Anne-Sophie Denommé-Pichon Anne-Sophie Denommé-Pichon Antonio Vitobello Antonio Vitobello Arthur Sorlin Arthur Sorlin Hana Safraou Hana Safraou Sophie Nambot Julian Delanne Sebastien Moutton Caroline Racine Camille Engel Melchior De Giraud d’Agay Daphne Lehalle Alice Goldenberg Alice Goldenberg Marjolaine Willems Christine Coubes David Genevieve Alain Verloes Alain Verloes Yline Capri Laurence Perrin Marie-Line Jacquemont Laetitia Lambert Elodie Lacaze Julien Thevenon Nadine Hana Nadine Hana Julien Van-Gils Charlotte Dubucs Varoona Bizaoui Marion Gerard-Blanluet James Lespinasse Sandra Mercier Anne-Marie Guerrot Anne-Marie Guerrot Isabelle Maystadt Emilie Tisserant Laurence Faivre Laurence Faivre Christophe Philippe Christophe Philippe Yannis Duffourd Yannis Duffourd Christel Thauvin-Robinet Christel Thauvin-Robinet Christel Thauvin-Robinet Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis Frontiers in Genetics GREP intellectual disability developmental anomalies genomic database diagnostic improvement exome sequencing (ES) |
| title | Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| title_full | Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| title_fullStr | Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| title_full_unstemmed | Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| title_short | Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| title_sort | combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis |
| topic | GREP intellectual disability developmental anomalies genomic database diagnostic improvement exome sequencing (ES) |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1122985/full |
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