Publications

Authors:

Ferrarini, Alberto; Xumerle, Luciano; Griggio, Francesca; Garonzi, Marianna; Cantaloni, Chiara; Centomo, Cesare; Vargas, Sergio Marin; Descombes, Patrick; Marquis, Julien; Collino, Sebastiano; Franceschi, Claudio; Garagnani, Paolo; Salisbury, Benjamin A; Harvey, John Max; Delledonne, Massimo

Title:

The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data

Year:

2015

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

PLoS ONE

ISSN of journal:

1932-6203

N° Volume:

10

Number or Folder:

7

Page numbers:

e0132180-e0132180

Keyword:

gvcf, variants, ngs

Short description of contents:

Genetic testing, which is now a routine part of clinical practice and disease management protocols, is often based on the assessment of small panels of variants or genes. On the other hand, continuous improvements in the speed and per-base costs of sequencing have now made whole exome sequencing (WES) and whole genome sequencing (WGS) viable strategies for targeted or complete genetic analysis, respectively. Standard WGS/WES data analytical workflows generally rely on calling of sequence variants respect to the reference genome sequence. However, the reference genome sequence contains a large number of sites represented by rare alleles, by known pathogenic alleles and by alleles strongly associated to disease by GWAS. It's thus critical, for clinical applications of WGS and WES, to interpret whether non-variant sites are homozygous for the reference allele or if the corresponding genotype cannot be reliably called. Here we show that an alternative analytical approach based on the analysis of both variant and non-variant sites from WGS data allows to genotype more than 92% of sites corresponding to known SNPs compared to 6% genotyped by standard variant analysis. These include homozygous reference sites of clinical interest, thus leading to a broad and comprehensive characterization of variation necessary to an accurate evaluation of disease risk. Altogether, our findings indicate that characterization of both variant and non-variant clinically informative sites in the genome is necessary to allow an accurate clinical assessment of a personal genome. Finally, we propose a highly efficient extended VCF (eVCF) file format which allows to store genotype calls for sites of clinical interest while remaining compatible with current variant interpretation software.

Product ID:

90887

Handle IRIS:

11562/936186

Last Modified:

November 15, 2022

Bibliographic citation:

Ferrarini, Alberto; Xumerle, Luciano; Griggio, Francesca; Garonzi, Marianna; Cantaloni, Chiara; Centomo, Cesare; Vargas, Sergio Marin; Descombes, Patrick; Marquis, Julien; Collino, Sebastiano; Franceschi, Claudio; Garagnani, Paolo; Salisbury, Benjamin A; Harvey, John Max; Delledonne, Massimo, The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data «PLoS ONE» , vol. 10 , n. 7 , 2015 , pp. e0132180-e0132180

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