SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants

With the advent of genomic sequencing, a number of balanced and unbalanced structural variants (SVs) can be detected per individual. Mainly due to incompleteness and the scattered nature of the available annotation data of the human genome, manual interpretation of the SV’s clinical significance is...

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Autores principales:	Joana Fino, Bárbara Marques, Zirui Dong, Dezső David
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SVInterpreter bioinformatic web-tool clinical outcome prediction balanced structural variants copy number variants topologically associated domains Genetics QH426-470
Acceso en línea:	https://doaj.org/article/6555536d80f64cf38396277b19c4f759
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spelling	oai:doaj.org-article:6555536d80f64cf38396277b19c4f7592021-12-01T23:24:58ZSVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants1664-802110.3389/fgene.2021.757170https://doaj.org/article/6555536d80f64cf38396277b19c4f7592021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.757170/fullhttps://doaj.org/toc/1664-8021With the advent of genomic sequencing, a number of balanced and unbalanced structural variants (SVs) can be detected per individual. Mainly due to incompleteness and the scattered nature of the available annotation data of the human genome, manual interpretation of the SV’s clinical significance is laborious and cumbersome. Since bioinformatic tools developed for this task are limited, a comprehensive tool to assist clinical outcome prediction of SVs is warranted. Herein, we present SVInterpreter, a free Web application, which analyzes both balanced and unbalanced SVs using topologically associated domains (TADs) as genome units. Among others, gene-associated data (as function and dosage sensitivity), phenotype similarity scores, and copy number variants (CNVs) scoring metrics are retrieved for an informed SV interpretation. For evaluation, we retrospectively applied SVInterpreter to 97 balanced (translocations and inversions) and 125 unbalanced (deletions, duplications, and insertions) previously published SVs, and 145 SVs identified from 20 clinical samples. Our results showed the ability of SVInterpreter to support the evaluation of SVs by (1) confirming more than half of the predictions of the original studies, (2) decreasing 40% of the variants of uncertain significance, and (3) indicating several potential position effect events. To our knowledge, SVInterpreter is the most comprehensive TAD-based tool to identify the possible disease-causing candidate genes and to assist prediction of the clinical outcome of SVs. SVInterpreter is available at http://dgrctools-insa.min-saude.pt/cgi-bin/SVInterpreter.py.Joana FinoBárbara MarquesZirui DongZirui DongZirui DongDezső DavidFrontiers Media S.A.articleSVInterpreterbioinformatic web-toolclinical outcome predictionbalanced structural variantscopy number variantstopologically associated domainsGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SVInterpreter bioinformatic web-tool clinical outcome prediction balanced structural variants copy number variants topologically associated domains Genetics QH426-470
spellingShingle	SVInterpreter bioinformatic web-tool clinical outcome prediction balanced structural variants copy number variants topologically associated domains Genetics QH426-470 Joana Fino Bárbara Marques Zirui Dong Zirui Dong Zirui Dong Dezső David SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
description	With the advent of genomic sequencing, a number of balanced and unbalanced structural variants (SVs) can be detected per individual. Mainly due to incompleteness and the scattered nature of the available annotation data of the human genome, manual interpretation of the SV’s clinical significance is laborious and cumbersome. Since bioinformatic tools developed for this task are limited, a comprehensive tool to assist clinical outcome prediction of SVs is warranted. Herein, we present SVInterpreter, a free Web application, which analyzes both balanced and unbalanced SVs using topologically associated domains (TADs) as genome units. Among others, gene-associated data (as function and dosage sensitivity), phenotype similarity scores, and copy number variants (CNVs) scoring metrics are retrieved for an informed SV interpretation. For evaluation, we retrospectively applied SVInterpreter to 97 balanced (translocations and inversions) and 125 unbalanced (deletions, duplications, and insertions) previously published SVs, and 145 SVs identified from 20 clinical samples. Our results showed the ability of SVInterpreter to support the evaluation of SVs by (1) confirming more than half of the predictions of the original studies, (2) decreasing 40% of the variants of uncertain significance, and (3) indicating several potential position effect events. To our knowledge, SVInterpreter is the most comprehensive TAD-based tool to identify the possible disease-causing candidate genes and to assist prediction of the clinical outcome of SVs. SVInterpreter is available at http://dgrctools-insa.min-saude.pt/cgi-bin/SVInterpreter.py.
format	article
author	Joana Fino Bárbara Marques Zirui Dong Zirui Dong Zirui Dong Dezső David
author_facet	Joana Fino Bárbara Marques Zirui Dong Zirui Dong Zirui Dong Dezső David
author_sort	Joana Fino
title	SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
title_short	SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
title_full	SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
title_fullStr	SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
title_full_unstemmed	SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants
title_sort	svinterpreter: a comprehensive topologically associated domain-based clinical outcome prediction tool for balanced and unbalanced structural variants
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6555536d80f64cf38396277b19c4f759
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SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants

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