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Phenotype-aware prioritisation of rare Mendelian disease variants
A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950798/ https://www.ncbi.nlm.nih.gov/pubmed/35934592 http://dx.doi.org/10.1016/j.tig.2022.07.002 |
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author | Kelly, Catherine Szabo, Anita Pontikos, Nikolas Arno, Gavin Robinson, Peter N. Jacobsen, Jules O.B. Smedley, Damian Cipriani, Valentina |
author_facet | Kelly, Catherine Szabo, Anita Pontikos, Nikolas Arno, Gavin Robinson, Peter N. Jacobsen, Jules O.B. Smedley, Damian Cipriani, Valentina |
author_sort | Kelly, Catherine |
collection | PubMed |
description | A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic odyssey, but performance statistics on real patient data are limited. Here we identify, assess, and compare the performance of all up-to-date, freely available, and programmatically accessible tools using a whole-exome, retinal disease dataset from 134 individuals with a molecular diagnosis. All tools were able to identify around two-thirds of the genetic diagnoses as the top-ranked candidate, with LIRICAL performing best overall. Finally, we discuss the challenges to overcome most cases remaining undiagnosed after current, state-of-the-art practices. |
format | Online Article Text |
id | pubmed-9950798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-99507982023-02-24 Phenotype-aware prioritisation of rare Mendelian disease variants Kelly, Catherine Szabo, Anita Pontikos, Nikolas Arno, Gavin Robinson, Peter N. Jacobsen, Jules O.B. Smedley, Damian Cipriani, Valentina Trends Genet Article A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic odyssey, but performance statistics on real patient data are limited. Here we identify, assess, and compare the performance of all up-to-date, freely available, and programmatically accessible tools using a whole-exome, retinal disease dataset from 134 individuals with a molecular diagnosis. All tools were able to identify around two-thirds of the genetic diagnoses as the top-ranked candidate, with LIRICAL performing best overall. Finally, we discuss the challenges to overcome most cases remaining undiagnosed after current, state-of-the-art practices. 2022-12 2022-08-04 /pmc/articles/PMC9950798/ /pubmed/35934592 http://dx.doi.org/10.1016/j.tig.2022.07.002 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Kelly, Catherine Szabo, Anita Pontikos, Nikolas Arno, Gavin Robinson, Peter N. Jacobsen, Jules O.B. Smedley, Damian Cipriani, Valentina Phenotype-aware prioritisation of rare Mendelian disease variants |
title | Phenotype-aware prioritisation of rare Mendelian disease variants |
title_full | Phenotype-aware prioritisation of rare Mendelian disease variants |
title_fullStr | Phenotype-aware prioritisation of rare Mendelian disease variants |
title_full_unstemmed | Phenotype-aware prioritisation of rare Mendelian disease variants |
title_short | Phenotype-aware prioritisation of rare Mendelian disease variants |
title_sort | phenotype-aware prioritisation of rare mendelian disease variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950798/ https://www.ncbi.nlm.nih.gov/pubmed/35934592 http://dx.doi.org/10.1016/j.tig.2022.07.002 |
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