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Analysis of institutional authors

Munte, EAuthorFeliubadalo, LAuthorDel Valle, JAuthorGonzalez, SAuthorBrunet, JAuthorCapella, GAuthorLazaro, CCorresponding AuthorPineda, MCorresponding Author

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November 21, 2024
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Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data

Publicated to:Journal Of Molecular Diagnostics. 26 (8): 727-738 - 2024-08-01 26(8), DOI: 10.1016/j.jmoldx.2024.05.005

Authors: Munté, E; Feliubadaló, L; Del Valle, J; González, S; Ramos-Muntada, M; Balmaña, J; Ramon y Caja, T; Tuset, N; Llort, G; Cadiñanos, J; Brunet, J; Capellá, G; Lázaro, C; Pineda, M

Affiliations

Fdn Ctr Med Asturias IMOMA, R&D Lab - Author
Hosp Arnau Vilanova, Med Oncol Dept - Author
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Familial Canc Clin - Author
Hosp Univ Parc Tauli Sabadell, Dept Med Oncol Parc Tauli - Author
Inst Invest Biomed Bellvitge, Mol Mech & Expt Therapy Oncol Program, Hereditary Canc Grp - Author
Inst Invest Biomed Girona, Precis Oncol Grp OncoGir Pro - Author
Inst Salud Carlos III, Ciber Oncol - Author
Univ Hosp Vall dHebron, Med Oncol Dept - Author
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Abstract

The molecular diagnosis of mismatch repair- de fi cient cancer syndromes is hampered by difficulties fi culties in sequencing the PMS2 gene, mainly owing to the PMS2CL pseudogene. Next-generation sequencing short reads cannot be mapped unambiguously by standard pipelines, compromising variant calling accuracy. This study aimed to provide a refined fi ned bioinformatic pipeline for PMS2 mutational analysis and explore PMS2 germline pathogenic variant prevalence in an unselected hereditary cancer (HC) cohort. PMS2 mutational analysis was optimized using two cohorts: 192 unselected HC patients for assessing the allelic ratio of paralogous sequence variants, and 13 samples enriched with PMS2 (likely) pathogenic variants screened previously by long-range genomic DNA PCR amplification. fi cation. Reads were forced to align with the PMS2 reference sequence, except those corresponding to exon 11, where only those intersecting gene-specific fi c invariant positions were considered. Afterward, the refined fi ned pipeline's accuracy was validated in a cohort of 40 patients and used to screen 5619 HC patients. Compared with our routine diagnostic pipeline, the PMS2_vaR pipeline showed increased technical sensitivity (0.853 to 0.956, respectively) in the validation cohort, identifying all previously PMS2 pathogenic variants found by long-range genomic DNA PCR amplification. fi cation. Fifteen HC cohort samples carried a pathogenic PMS2 variant (15 of 5619; 0.285%), doubling the estimated prevalence in the general population. The refined fi ned open-source approach improved PMS2 mutational analysis accuracy, allowing its inclusion in the routine next-generation sequencing pipeline streamlining PMS2 screening. (J Mol Diagn 2024, 26: 727-738; https://doi.org/10.1016/j.jmoldx.2024.05.005)

Keywords

ArticleBioinformaticsCancer patientCohort analysisComputational biologyControlled studyDiagnosisDiagnostic test accuracy studyDna mutational analysisExonGenetic screeningGenetic testingGenetic variabilityGeneticsGenomic dnaGerm-line mutationGermline mutationHereditary tumor syndromeHigh throughput sequencingHigh-throughput nucleotide sequencingHumanHumansLynch-syndromeMajor clinical studyMismatch repair deficiencyMismatch repair endonuclease pms2Mismatch repair protein pms2Mutation detectionMutational analysisNeoplastic syndromes, hereditaryPms2 protein, humanPolymerase chain reactionPredictive valueProceduresProteinRecommendationsSensitivity and specificity

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Molecular Diagnostics 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, 2024 there are still no calculated indicators, but in 2023, it was in position 22/88, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pathology.

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 2025-07-10:

  • 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: 9.
  • 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: 13.6.
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).
  • The number of mentions in news outlets: 1 (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 (MUNTÉ ROCA, ELISABET) and Last Author (PINEDA RIU, MARTA).

the authors responsible for correspondence tasks have been Lazaro Garcia, Concepcion and PINEDA RIU, MARTA.