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Analysis of institutional authors

Muñoz-Pujol GAuthorUgarteburu OAuthorSegur-Bailach EAuthorJurado SAuthorGarrabou GAuthorGuitart-Mampel MAuthorGarcía-Villoria JAuthorRibes ACorresponding AuthorTort FCorresponding Author
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Article

CRISPR/Cas9-based functional genomics strategy to decipher the pathogenicity of genetic variants in inherited metabolic disorders

Publicated to:Journal Of Inherited Metabolic Disease. 46 (6): 1029-1042 - 2023-11-01 46(6), DOI: 10.1002/jimd.12681

Authors: Munoz-Pujol, Gerard; Ugarteburu, Olatz; Segur-Bailach, Eulalia; Moliner, Sonia; Jurado, Susana; Garrabou, Gloria; Guitart-Mampel, Mariona; Garcia-Villoria, Judit; Artuch, Rafael; Fons, Carme; Ribes, Antonia; Tort, Frederic

Affiliations

CIBERER, Barcelona, Spain - Author
Clinical Biochemistry and Molecular Medicine and Genetics Departments, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, and CIBERER, Esplugues de Llobregat, Barcelona, Spain. - Author
Hosp Clin Barcelona, Seccio Errors Congenits Metab IBC, Serv Bioquim & Genet Mol, IDIBAPS,CIBERER, Barcelona, Spain - Author
Hosp St Joan Deu, Inst Recerca St Joan Deu, Clin Biochem Dept, Barcelona, Spain - Author
Hosp St Joan Deu, Inst Recerca St Joan Deu, Mol Med & Genet Dept, Barcelona, Spain - Author
Hosp St Joan Deu, Inst Recerca, Neurol Dept, Fetal Neonatal Neurol & Early Epilepsy Unit, Barcelona, Spain - Author
Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic de Barcelona, IDIBAPS, CIBERER, Barcelona, Spain. - Author
Univ Barcelona, Hosp Clin Barcelona, Fac Med & Hlth Sci, Internal Med Serv,Inherited Metab Dis & Muscle Dis, Barcelona, Spain - Author
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Abstract

The determination of the functional impact of variants of uncertain significance (VUS) is one of the major bottlenecks in the diagnostic workflow of inherited genetic diseases. To face this problem, we set up a CRISPR/Cas9-based strategy for knock-in cellular model generation, focusing on inherited metabolic disorders (IMDs). We selected variants in seven IMD-associated genes, including seven reported disease-causing variants and four benign/likely benign variants. Overall, 11 knock-in cell models were generated via homology-directed repair in HAP1 haploid cells using CRISPR/Cas9. The functional impact of the variants was determined by analyzing the characteristic biochemical alterations of each disorder. Functional studies performed in knock-in cell models showed that our approach accurately distinguished the functional effect of pathogenic from non-pathogenic variants in a reliable manner in a wide range of IMDs. Our study provides a generic approach to assess the functional impact of genetic variants to improve IMD diagnosis and this tool could emerge as a promising alternative to invasive tests, such as muscular or skin biopsies. Although the study has been performed only in IMDs, this strategy is generic and could be applied to other genetic disorders. © 2023 SSIEM.

Keywords
ArticleCell modelsControlled studyCrispr cas systemCrispr-cas systemsCrispr-cas9 systemCrispr/cas9Evaluation studyFunctional genomicsGeneGene identificationGenetic associationGenetic variabilityGeneticsGenomicsHap1HaploidyHomology directed repairHumanHuman cellHumansInherited metabolic disordersKnock-inMetabolic diseasesMetabolic disorderPathogenicityVariant of uncertain significanceVirulence

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Inherited Metabolic Disease due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 37/191, thus managing to position itself as a Q1 (Primer Cuartil), in the category Genetics & Heredity.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-29:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 11.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 11 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.9.
  • The number of mentions on the social network X (formerly Twitter): 14 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Muñoz Pujol, Gerard) and Last Author (Tort Escalé, Frederic).

the authors responsible for correspondence tasks have been Ribes Rubio, Antonia and Tort Escalé, Frederic.