학술논문
Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis
Document Type
article
Author
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 De Giraud d’Agay; Daphne Lehalle; Alice Goldenberg; Marjolaine Willems; Christine Coubes; David Genevieve; Alain Verloes; Yline Capri; Laurence Perrin; Marie-Line Jacquemont; Laetitia Lambert; Elodie Lacaze; Julien Thevenon; Nadine Hana; Julien Van-Gils; Charlotte Dubucs; Varoona Bizaoui; Marion Gerard-Blanluet; James Lespinasse; Sandra Mercier; Anne-Marie Guerrot; Isabelle Maystadt; Emilie Tisserant; Laurence Faivre; Christophe Philippe; Yannis Duffourd; Christel Thauvin-Robinet
Source
Frontiers in Genetics, Vol 14 (2023)
Subject
Language
English
ISSN
1664-8021
Abstract
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.