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The Globally search for a Regular Expression and Print matching lines (GREP) strategy: an innovative reanalysis strategy combining bibliographic monitoring with fast GREP directly applied to a massive genomic database to rapidly improve diagnosis
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  • Frédéric Tran Mau Them,
  • Alexis Overs,
  • ange-line bruel,
  • Romain Duquet,
  • Mylene Thareau,
  • Anne-Sophie Denommé-Pichon,
  • Antonio Vitobello,
  • Arthur Sorlin,
  • Hana Safraou,
  • Sophie Nambot,
  • Julian Delanne,
  • Sebastien Moutton,
  • Caroline RACINE,
  • Camille Engel,
  • Melchior D’agay,
  • Daphné Lehalle,
  • Alice Goldenberg,
  • Marjolaine Willems,
  • christine Coubes,
  • David Geneviève,
  • Alain Verloes,
  • Yline CAPRI,
  • Laurence Perrin,
  • Marie-Line Jacquemont,
  • Laetitia Lambert,
  • Elodie Lacaze,
  • Julien Thevenon,
  • Nadine Hanna,
  • Van-Gils Julien,
  • Charlotte Dubucs,
  • Varoona Bizaoui,
  • Marion Gerard,
  • James Lespinasse,
  • Sandra Mercier,
  • Anne-Marie Guerrot,
  • Isabelle Maystadt,
  • Emilie Tisserant,
  • Laurence Faivre,
  • Christophe Philippe,
  • Yannis Duffourd,
  • Christel Thauvin-Robinet
Frédéric Tran Mau Them
Centre Hospitalier Universitaire Dijon Bourgogne

Corresponding Author:frederic.tran-mau-them@u-bourgogne.fr

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Alexis Overs
Centre Hospitalier Universitaire Dijon Bourgogne
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ange-line bruel
Centre Hospitalier Universitaire Dijon Bourgogne
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Romain Duquet
Centre Hospitalier Universitaire Dijon Bourgogne
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Mylene Thareau
Centre Hospitalier Universitaire Dijon Bourgogne
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Anne-Sophie Denommé-Pichon
Centre Hospitalier Universitaire Dijon Bourgogne
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Antonio Vitobello
Centre Hospitalier Universitaire Dijon Bourgogne
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Arthur Sorlin
Centre Hospitalier Universitaire Dijon Bourgogne
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Hana Safraou
Centre Hospitalier Universitaire Dijon Bourgogne
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Sophie Nambot
Centre Hospitalier Universitaire Dijon Bourgogne
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Julian Delanne
Centre Hospitalier Universitaire Dijon Bourgogne
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Sebastien Moutton
Centre Hospitalier Universitaire Dijon Bourgogne
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Caroline RACINE
Centre Hospitalier Universitaire Dijon Bourgogne
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Camille Engel
Centre Hospitalier Universitaire Dijon Bourgogne
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Melchior D’agay
Centre Hospitalier Universitaire Dijon Bourgogne
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Daphné Lehalle
Centre Hospitalier Universitaire Dijon Bourgogne
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Alice Goldenberg
Centre Hospitalier Universitaire de Rouen
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Marjolaine Willems
Centre Hospitalier Regional Universitaire de Montpellier
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christine Coubes
Centre Hospitalier Regional Universitaire de Montpellier
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David Geneviève
Centre Hospitalier Regional Universitaire de Montpellier
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Alain Verloes
Hopital Universitaire Robert-Debre Departement de genetique
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Yline CAPRI
Hopital Universitaire Robert-Debre Unite fonctionnelle de genetique clinique
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Laurence Perrin
Hopital Universitaire Robert-Debre Unite fonctionnelle de genetique clinique
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Marie-Line Jacquemont
Centre Hospitalier Universitaire de La Reunion Sites Sud Saint-Pierre
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Laetitia Lambert
Centre hospitalier regional universitaire de Nancy
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Elodie Lacaze
Groupe Hospitalier du Havre
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Julien Thevenon
Centre Hospitalier Universitaire Dijon Bourgogne
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Nadine Hanna
Hopital Bichat - Claude-Bernard
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Van-Gils Julien
Centre Hospitalier Universitaire de Bordeaux
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Charlotte Dubucs
Centre Hospitalier Universitaire de Toulouse
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Varoona Bizaoui
Centre Hospitalier Universitaire de Caen
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Marion Gerard
Centre Hospitalier Universitaire de Caen
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James Lespinasse
Centre Hospitalier Metropole Savoie
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Sandra Mercier
Centre Hospitalier Universitaire de Nantes
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Anne-Marie Guerrot
Centre Hospitalier Universitaire de Rouen
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Isabelle Maystadt
Institut de Pathologie et de Genetique asbl
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Emilie Tisserant
Centre Hospitalier Universitaire Dijon Bourgogne
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Laurence Faivre
Centre Hospitalier Universitaire Dijon Bourgogne
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Christophe Philippe
Centre Hospitalier Universitaire Dijon Bourgogne
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Yannis Duffourd
Centre Hospitalier Universitaire Dijon Bourgogne
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Christel Thauvin-Robinet
Centre Hospitalier Universitaire Dijon Bourgogne
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Abstract

Purpose: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Prospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories. We applied a reanalysis strategy based on intensive prospective bibliographic monitoring, and directly applied the Globally search for a Regular Expression and Print matching lines (GREP) command-line to a massive ES database. Methods: For 18 months, we submitted daily the same 5 keywords of interest (( intellectual disability, ( neuro)developmental delay, (neuro)developmental disorder)) to PubMed, to identify recently published, novel disease-gene associations, or new phenotypes in genes already implicated in human pathology. We used the Linux GREP command-line and an in-house script, to collect all variants in these genes from our 5459 exome database. Results: We grepped 128 genes and collected 56 candidate variants in 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, we confirmed pathogenicity in 21/2875 undiagnosed affected probands (0.7%). Conclusion: The GREP command-line is efficient, and less tedious than complete periodical reanalysis. It is an interesting reanalysis strategy to improve diagnosis.