Cargando…

Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy

With the advent of next-generation whole genome sequencing, many variants of uncertain significance (VUS) have been identified in individuals suffering from inheritable hypertrophic cardiomyopathy (HCM). Unfortunately, this classification of a genetic variant results in ambiguity in interpretation,...

Descripción completa

Detalles Bibliográficos
Autores principales: Doh, Chang Yoon, Kampourakis, Thomas, Campbell, Kenneth S., Stelzer, Julian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432852/
https://www.ncbi.nlm.nih.gov/pubmed/37600050
http://dx.doi.org/10.3389/fcvm.2023.1238515
_version_ 1785091517328654336
author Doh, Chang Yoon
Kampourakis, Thomas
Campbell, Kenneth S.
Stelzer, Julian E.
author_facet Doh, Chang Yoon
Kampourakis, Thomas
Campbell, Kenneth S.
Stelzer, Julian E.
author_sort Doh, Chang Yoon
collection PubMed
description With the advent of next-generation whole genome sequencing, many variants of uncertain significance (VUS) have been identified in individuals suffering from inheritable hypertrophic cardiomyopathy (HCM). Unfortunately, this classification of a genetic variant results in ambiguity in interpretation, risk stratification, and clinical practice. Here, we aim to review some basic science methods to gain a more accurate characterization of VUS in HCM. Currently, many genomic data-based computational methods have been developed and validated against each other to provide a robust set of resources for researchers. With the continual improvement in computing speed and accuracy, in silico molecular dynamic simulations can also be applied in mutational studies and provide valuable mechanistic insights. In addition, high throughput in vitro screening can provide more biologically meaningful insights into the structural and functional effects of VUS. Lastly, multi-level mathematical modeling can predict how the mutations could cause clinically significant organ-level dysfunction. We discuss emerging technologies that will aid in better VUS characterization and offer a possible basic science workflow for exploring the pathogenicity of VUS in HCM. Although the focus of this mini review was on HCM, these basic science methods can be applied to research in dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic cardiomyopathy (ACM), or other genetic cardiomyopathies.
format Online
Article
Text
id pubmed-10432852
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-104328522023-08-18 Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy Doh, Chang Yoon Kampourakis, Thomas Campbell, Kenneth S. Stelzer, Julian E. Front Cardiovasc Med Cardiovascular Medicine With the advent of next-generation whole genome sequencing, many variants of uncertain significance (VUS) have been identified in individuals suffering from inheritable hypertrophic cardiomyopathy (HCM). Unfortunately, this classification of a genetic variant results in ambiguity in interpretation, risk stratification, and clinical practice. Here, we aim to review some basic science methods to gain a more accurate characterization of VUS in HCM. Currently, many genomic data-based computational methods have been developed and validated against each other to provide a robust set of resources for researchers. With the continual improvement in computing speed and accuracy, in silico molecular dynamic simulations can also be applied in mutational studies and provide valuable mechanistic insights. In addition, high throughput in vitro screening can provide more biologically meaningful insights into the structural and functional effects of VUS. Lastly, multi-level mathematical modeling can predict how the mutations could cause clinically significant organ-level dysfunction. We discuss emerging technologies that will aid in better VUS characterization and offer a possible basic science workflow for exploring the pathogenicity of VUS in HCM. Although the focus of this mini review was on HCM, these basic science methods can be applied to research in dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic cardiomyopathy (ACM), or other genetic cardiomyopathies. Frontiers Media S.A. 2023-08-01 /pmc/articles/PMC10432852/ /pubmed/37600050 http://dx.doi.org/10.3389/fcvm.2023.1238515 Text en © 2023 Doh, Kampourakis, Campbell and Stelzer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Doh, Chang Yoon
Kampourakis, Thomas
Campbell, Kenneth S.
Stelzer, Julian E.
Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title_full Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title_fullStr Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title_full_unstemmed Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title_short Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
title_sort basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432852/
https://www.ncbi.nlm.nih.gov/pubmed/37600050
http://dx.doi.org/10.3389/fcvm.2023.1238515
work_keys_str_mv AT dohchangyoon basicsciencemethodsforthecharacterizationofvariantsofuncertainsignificanceinhypertrophiccardiomyopathy
AT kampourakisthomas basicsciencemethodsforthecharacterizationofvariantsofuncertainsignificanceinhypertrophiccardiomyopathy
AT campbellkenneths basicsciencemethodsforthecharacterizationofvariantsofuncertainsignificanceinhypertrophiccardiomyopathy
AT stelzerjuliane basicsciencemethodsforthecharacterizationofvariantsofuncertainsignificanceinhypertrophiccardiomyopathy