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VarQ: a tool for the structural and functional analysis of human protein variants

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dc.contributor.author Radusky, Leandro
dc.contributor.author Modenutti, Carlos
dc.contributor.author Delgado Blanco, Javier
dc.contributor.author Bustamante, Juan P.
dc.contributor.author Vishnopolska, Sebastian
dc.contributor.author Kiel, Christina
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.contributor.author Marti, Marcelo
dc.contributor.author Turjanski, Adrián
dc.date.accessioned 2019-11-15T08:12:54Z
dc.date.available 2019-11-15T08:12:54Z
dc.date.issued 2018
dc.identifier.citation Radusky L, Modenutti C, Delgado J, Bustamante JP, Vishnopolska S, Kiel C, Serrano L, Marti M, Turjanski A. VarQ: a tool for the structural and functional analysis of human protein variants. Front Genet. 2018; 9:620. DOI 10.3389/fgene.2018.00620
dc.identifier.issn 1664-8021
dc.identifier.uri http://hdl.handle.net/10230/42861
dc.description.abstract Understanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Despite the existence of several bioinformatic algorithms and servers that predict if a SAS is pathogenic or not, they give little or no information at all on the reasons for pathogenicity prediction and on the actual predicted effect of the SAS on the protein function. Moreover, few actual methods take into account structural information when available for automated analysis. Moreover, many of these algorithms are able to predict an effect that no necessarily translates directly into pathogenicity. VarQ is a bioinformatic pipeline that incorporates structural information for the detailed analysis and prediction of SAS effect on protein function. It is an online tool which uses UniProt id and automatically analyzes known and user provided SAS for their effect on protein activity, folding, aggregation and protein interactions, among others. We show that structural information, when available, can improve the SAS pathogenicity diagnosis and more important explain its causes. We show that VarQ is able to correctly reproduce previous analysis of RASopathies related mutations, saving extensive and time consuming manual curation. VarQ assessment was performed over a set of previously manually curated RASopathies (diseases that affects the RAS/MAPK signaling pathway) related variants, showing its ability to correctly predict the phenotypic outcome and its underlying cause. This resource is available online at http://varq.qb.fcen.uba.ar/. Supporting Information & Tutorials may be found in the webpage of the tool.
dc.description.sponsorship The research leading to these results has received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement Nr. PRIMES_278568. This work was supported by the Spanish Ministerio de Economía y Competitividad, Plan Nacional BIO2012-39754 and the European Fund for Regional Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work has been supported by grant PIP1220110100850 awarded to MM, and by PICT-2010-2805 awarded to AT. This project has received funding from the Marie Curie International Research Staff Exchange Scheme within the 7th European Community Framework Program under grant agreement no. 612583-DEANN. CABANA is funded by the BBSRC under The Global Challenges Research Fund (GCRF) Growing Research Capability call, contract number BB/P027849/1 (www.ukri.org/research/global-challenges-research-fund/funded-projects/).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Genet. 2018; 9:620
dc.rights © 2018 Radusky, Modenutti, Delgado, Bustamante, Vishnopolska, Kiel, Serrano, Marti and Turjanski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://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.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title VarQ: a tool for the structural and functional analysis of human protein variants
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fgene.2018.00620
dc.subject.keyword Variation diagnosis
dc.subject.keyword Bioinformatics
dc.subject.keyword Web server
dc.subject.keyword Single amino acid substitutions
dc.subject.keyword Single amino acid substitutions classification
dc.subject.keyword FoldX
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/278568
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2012-39754
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/612583
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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