TY - JOUR
T1 - Aminode
T2 - Identification of Evolutionary Constraints in the Human Proteome
AU - Chang, Kevin T.
AU - Guo, Junyan
AU - Di Ronza, Alberto
AU - Sardiello, Marco
N1 - Funding Information:
We thank Dr. Michael Kohn for helpful suggestions and critical reading of the manuscript. This work was supported by NIH grant NS079618 to M.S. and by a grant from the Beyond Batten Disease Foundation to M.S.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040927551&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-19744-w
DO - 10.1038/s41598-018-19744-w
M3 - Article
C2 - 29358731
AN - SCOPUS:85040927551
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1357
ER -