{"id":549,"date":"2018-12-12T11:40:42","date_gmt":"2018-12-12T10:40:42","guid":{"rendered":"https:\/\/www.personalgenomics.it\/en\/?p=549"},"modified":"2022-07-25T11:15:44","modified_gmt":"2022-07-25T09:15:44","slug":"the-use-of-non-variant-sites-to-improve-the-clinical-assessment-of-whole-genome-sequence-data","status":"publish","type":"post","link":"https:\/\/www.personalgenomics.it\/en\/the-use-of-non-variant-sites-to-improve-the-clinical-assessment-of-whole-genome-sequence-data\/","title":{"rendered":"The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"background-color: rgba(255,255,255,0);background-position: center center;background-repeat: no-repeat;border-width: 0px 0px 0px 0px;border-color:#eae9e9;border-style:solid;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start\" style=\"max-width:1352px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column\"><div class=\"fusion-column-wrapper fusion-flex-justify-content-flex-start fusion-content-layout-column\" style=\"background-position:left top;background-repeat:no-repeat;-webkit-background-size:cover;-moz-background-size:cover;-o-background-size:cover;background-size:cover;padding: 0px 0px 0px 0px;\"><style type=\"text\/css\">@media only screen and (max-width:1024px) {.fusion-title.fusion-title-1{margin-top:0px!important; margin-right:0px!important;margin-bottom:15px!important;margin-left:0px!important;}}@media only screen and (max-width:640px) {.fusion-title.fusion-title-1{margin-top:0px!important; margin-right:0px!important;margin-bottom:20px!important; margin-left:0px!important;}}<\/style><div class=\"fusion-title title fusion-title-1 fusion-sep-none fusion-title-text fusion-title-size-three\" style=\"margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;\"><h3 class=\"title-heading-left\" style=\"margin:0;\">The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data<\/h3><\/div><style type=\"text\/css\">@media only screen and (max-width:1024px) {.fusion-title.fusion-title-2{margin-top:0px!important; margin-right:0px!important;margin-bottom:15px!important;margin-left:0px!important;}}@media only screen and (max-width:640px) {.fusion-title.fusion-title-2{margin-top:0px!important; margin-right:0px!important;margin-bottom:20px!important; margin-left:0px!important;}}<\/style><div class=\"fusion-title title fusion-title-2 fusion-sep-none fusion-title-text fusion-title-size-five\" style=\"margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;\"><h5 class=\"title-heading-left\" style=\"margin:0;\">Genetic testing is often based on the assessment of small panels of variants or genes.<\/h5><\/div><div class=\"fusion-text fusion-text-1\"><p><em><strong>Authors:<\/strong> Ferrarini A, Xumerle L, Griggio F, Garonzi M, Cantaloni C, Centomo C, Vargas SM, Descombes P, Marquis J, Collino S, Franceschi C, Garagnani P, Salisbury BA, Harvey JM, Delledonne M.<\/em><br \/>\nPLoS One. 2015 Jul 6;10(7):e0132180.<\/p>\n<\/div><div class=\"fusion-text fusion-text-2\"><p>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\u2019s 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.<\/p>\n<\/div><div ><style>.fusion-body .fusion-button.button-1{border-radius:8px 8px 8px 8px;}<\/style><a class=\"fusion-button button-flat fusion-button-default-size button-default button-1 fusion-button-default-span fusion-button-default-type\" target=\"_blank\" rel=\"noopener noreferrer\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/261477\"><span class=\"fusion-button-text\">Read more<\/span><\/a><\/div><\/div><style type=\"text\/css\">.fusion-body .fusion-builder-column-0{width:100% !important;margin-top : 0px;margin-bottom : 0px;}.fusion-builder-column-0 > .fusion-column-wrapper {padding-top : 0px !important;padding-right : 0px !important;margin-right : 1.92%;padding-bottom : 0px !important;padding-left : 0px !important;margin-left : 1.92%;}@media only screen and (max-width:1024px) {.fusion-body .fusion-builder-column-0{width:100% !important;}.fusion-builder-column-0 > .fusion-column-wrapper {margin-right : 1.92%;margin-left : 1.92%;}}@media only screen and (max-width:640px) {.fusion-body .fusion-builder-column-0{width:100% !important;}.fusion-builder-column-0 > .fusion-column-wrapper {margin-right : 1.92%;margin-left : 1.92%;}}<\/style><\/div><\/div><style type=\"text\/css\">.fusion-body .fusion-flex-container.fusion-builder-row-1{ padding-top : 0px;margin-top : 0px;padding-right : 0px;padding-bottom : 0px;margin-bottom : 0px;padding-left : 0px;}<\/style><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[19],"tags":[],"_links":{"self":[{"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/posts\/549"}],"collection":[{"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/comments?post=549"}],"version-history":[{"count":4,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/posts\/549\/revisions"}],"predecessor-version":[{"id":2124,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/posts\/549\/revisions\/2124"}],"wp:attachment":[{"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/media?parent=549"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/categories?post=549"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.personalgenomics.it\/en\/wp-json\/wp\/v2\/tags?post=549"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}