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Aminode: Identification of Evolutionary Constraints in the Human Proteome
Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein’s structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778061/ https://www.ncbi.nlm.nih.gov/pubmed/29358731 http://dx.doi.org/10.1038/s41598-018-19744-w |
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author | Chang, Kevin T. Guo, Junyan di Ronza, Alberto Sardiello, Marco |
author_facet | Chang, Kevin T. Guo, Junyan di Ronza, Alberto Sardiello, Marco |
author_sort | Chang, Kevin T. |
collection | PubMed |
description | Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein’s structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins. The compilation and analysis of the datasets required to infer ECRs, however, are time consuming and require skills in coding and bioinformatics, which can limit the use of ECR analysis in the biomedical community. Here, we developed Aminode, a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is pre-loaded with the results of the analysis of the whole human proteome compared with proteomes from 62 additional vertebrate species. Profiles of the relative rates of amino acid substitution and ECR maps of human proteins are available for immediate search and download on the Aminode website. Aminode can also be used for custom analyses of protein families of interest. Interestingly, mapping of known missense variants shows great enrichment of pathogenic variants and depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that ECR analysis may help evaluate the potential pathogenicity of variants of unknown significance. Aminode is freely available at http://www.aminode.org. |
format | Online Article Text |
id | pubmed-5778061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57780612018-01-31 Aminode: Identification of Evolutionary Constraints in the Human Proteome Chang, Kevin T. Guo, Junyan di Ronza, Alberto Sardiello, Marco Sci Rep Article Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein’s structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins. The compilation and analysis of the datasets required to infer ECRs, however, are time consuming and require skills in coding and bioinformatics, which can limit the use of ECR analysis in the biomedical community. Here, we developed Aminode, a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is pre-loaded with the results of the analysis of the whole human proteome compared with proteomes from 62 additional vertebrate species. Profiles of the relative rates of amino acid substitution and ECR maps of human proteins are available for immediate search and download on the Aminode website. Aminode can also be used for custom analyses of protein families of interest. Interestingly, mapping of known missense variants shows great enrichment of pathogenic variants and depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that ECR analysis may help evaluate the potential pathogenicity of variants of unknown significance. Aminode is freely available at http://www.aminode.org. Nature Publishing Group UK 2018-01-22 /pmc/articles/PMC5778061/ /pubmed/29358731 http://dx.doi.org/10.1038/s41598-018-19744-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Chang, Kevin T. Guo, Junyan di Ronza, Alberto Sardiello, Marco Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title | Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title_full | Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title_fullStr | Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title_full_unstemmed | Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title_short | Aminode: Identification of Evolutionary Constraints in the Human Proteome |
title_sort | aminode: identification of evolutionary constraints in the human proteome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778061/ https://www.ncbi.nlm.nih.gov/pubmed/29358731 http://dx.doi.org/10.1038/s41598-018-19744-w |
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