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\begin{document}

\title{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}



\author[1]{Frédéric Tran Mau Them}%
\author[1]{Alexis Overs}%
\author[1]{ange-line bruel}%
\author[1]{Romain Duquet}%
\author[1]{Mylene Thareau}%
\author[1]{Anne-Sophie Denommé-Pichon}%
\author[1]{Antonio Vitobello}%
\author[1]{Arthur Sorlin}%
\author[1]{Hana Safraou}%
\author[1]{Sophie Nambot}%
\author[1]{Julian Delanne}%
\author[1]{Sebastien Moutton}%
\author[1]{Caroline RACINE}%
\author[1]{Camille Engel}%
\author[1]{Melchior D’agay}%
\author[1]{Daphné Lehalle}%
\author[2]{Alice Goldenberg}%
\author[3]{Marjolaine Willems}%
\author[3]{christine Coubes}%
\author[3]{David Geneviève}%
\author[4]{Alain Verloes}%
\author[5]{Yline CAPRI}%
\author[5]{Laurence Perrin}%
\author[6]{Marie-Line Jacquemont}%
\author[7]{Laetitia Lambert}%
\author[8]{Elodie Lacaze}%
\author[1]{Julien Thevenon}%
\author[9]{Nadine Hanna}%
\author[10]{Van-Gils Julien}%
\author[11]{Charlotte Dubucs}%
\author[12]{Varoona Bizaoui}%
\author[12]{Marion Gerard}%
\author[13]{James Lespinasse}%
\author[14]{Sandra Mercier}%
\author[2]{Anne-Marie Guerrot}%
\author[15]{Isabelle Maystadt}%
\author[1]{Emilie Tisserant}%
\author[1]{Laurence Faivre}%
\author[1]{Christophe Philippe}%
\author[1]{Yannis Duffourd}%
\author[1]{Christel Thauvin-Robinet}%
\affil[1]{Centre Hospitalier Universitaire Dijon Bourgogne}%
\affil[2]{Centre Hospitalier Universitaire de Rouen}%
\affil[3]{Centre Hospitalier Regional Universitaire de Montpellier}%
\affil[4]{Hopital Universitaire Robert-Debre Departement de genetique}%
\affil[5]{Hopital Universitaire Robert-Debre Unite fonctionnelle de genetique clinique}%
\affil[6]{Centre Hospitalier Universitaire de La Reunion Sites Sud Saint-Pierre}%
\affil[7]{Centre hospitalier regional universitaire de Nancy}%
\affil[8]{Groupe Hospitalier du Havre}%
\affil[9]{Hopital Bichat - Claude-Bernard}%
\affil[10]{Centre Hospitalier Universitaire de Bordeaux}%
\affil[11]{Centre Hospitalier Universitaire de Toulouse}%
\affil[12]{Centre Hospitalier Universitaire de Caen}%
\affil[13]{Centre Hospitalier Metropole Savoie}%
\affil[14]{Centre Hospitalier Universitaire de Nantes}%
\affil[15]{Institut de Pathologie et de Genetique asbl}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
\textbf{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. \textbf{Methods:} For 18 months,
we submitted daily the same 5 keywords of interest (( \emph{intellectual
disability}, ( \emph{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. \textbf{Results}: We \emph{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\%). \textbf{Conclusion}: The GREP command-line is
efficient, and less tedious than complete periodical reanalysis. It is
an interesting reanalysis strategy to improve diagnosis.%
\end{abstract}%



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\textbf{Hosted file}

\verb`GREP_final.docx`  available at \url{https://authorea.com/users/464395/articles/559305-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}\selectlanguage{english}
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