MoBiDiC Prioritization Algorithm, a Free, Accessible, and Efficient Pipeline for Single-Nucleotide Variant Annotation and Prioritization for Next-Generation Sequencing Routine Molecular Diagnosis
| Autor: | Sylvie Tuffery-Giraud, Michel Koenig, Raul Juntas Morales, David Baux, Charles Van Goethem, Mireille Cossée, Charly Mathieu, Vilma-Lotta Lehtokari, Kevin Yauy, Gisèle Bonne, Martin Krahn, Thomas Guignard, Delphine Lacourt, Henri Pegeot |
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| Přispěvatelé: | Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Computer science RNA Splicing In silico Mutation Missense High-Throughput Nucleotide Sequencing Molecular Sequence Annotation Molecular diagnostics Polymorphism Single Nucleotide DNA sequencing Pathology and Forensic Medicine 03 medical and health sciences Annotation 030104 developmental biology Molecular Diagnostic Techniques [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Humans Molecular Medicine Missense mutation Computer Simulation splice Algorithm Algorithms Exome sequencing Selection (genetic algorithm) |
| Zdroj: | Journal of Molecular Diagnostics Journal of Molecular Diagnostics, American Society for Investigative Pathology (ASIP), 2018, 20 (4), pp.465-473. ⟨10.1016/j.jmoldx.2018.03.009⟩ |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2018.03.009⟩ |
| Popis: | International audience; Interpretation of next-generation sequencing constitutes the main limitation of molecular diagnostics. In diagnosing myopathies and muscular dystrophies, another issue is efficiency in predicting the pathogenicity of variants identified in large genes, especially TTN; current in silico prediction tools show limitations in predicting and ranking the numerous variants of such genes. We propose a variant-prioritization tool, the MoBiDiC prioritization algorithm (MPA). MPA is based on curated interpretation of data on previously reported variants, biological assumptions, and splice and missense predictors, and is used to prioritize all types of single-nucleotide variants. MPA was validated by comparing its sensitivity and specificity to those of dbNSFP database prediction tools, using a data set composed of DYSF, DMD, LMNA, NEB, and TTN variants extracted from expert-reviewed and ExAC databases. MPA obtained the best annotation rates for missense and splice variants. As MPA aggregates the results from several predictors, individual predictor errors are counterweighted, improving the sensitivity and specificity of missense and splice variant predictions. We propose a sequential use of MPA, beginning with the selection of variants with higher scores and followed by, in the absence of candidate pathologic variants, consideration of variants with lower scores. We provide scripts and documentation for free academic use and a validated annotation pipeline scaled for panel and exome sequencing to prioritize single-nucleotide variants from a VCF file. |
| Databáze: | OpenAIRE |
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