How good are pathogenicity predictors in detecting benign variants?
PLoS Comput Biol
; 15(2): e1006481, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30742610
ABSTRACT
Computational tools are widely used for interpreting variants detected in sequencing projects. The choice of these tools is critical for reliable variant impact interpretation for precision medicine and should be based on systematic performance assessment. The performance of the methods varies widely in different performance assessments, for example due to the contents and sizes of test datasets. To address this issue, we obtained 63,160 common amino acid substitutions (allele frequency ≥1% and <25%) from the Exome Aggregation Consortium (ExAC) database, which contains variants from 60,706 genomes or exomes. We evaluated the specificity, the capability to detect benign variants, for 10 variant interpretation tools. In addition to overall specificity of the tools, we tested their performance for variants in six geographical populations. PON-P2 had the best performance (95.5%) followed by FATHMM (86.4%) and VEST (83.5%). While these tools had excellent performance, the poorest method predicted more than one third of the benign variants to be disease-causing. The results allow choosing reliable methods for benign variant interpretation, for both research and clinical purposes, as well as provide a benchmark for method developers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise de Sequência de DNA
/
Biologia Computacional
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Previsões
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article