Analysis and Interpretation of the Impact of Missense Variants in Cancer
Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this review we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-05-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/11/5416 |
id |
doaj-5a0b3dd509aa49b68568b223c8072a6f |
---|---|
record_format |
Article |
spelling |
doaj-5a0b3dd509aa49b68568b223c8072a6f2021-06-01T00:39:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01225416541610.3390/ijms22115416Analysis and Interpretation of the Impact of Missense Variants in CancerMaria Petrosino0Leonore Novak1Alessandra Pasquo2Roberta Chiaraluce3Paola Turina4Emidio Capriotti5Valerio Consalvi6Dipartimento Scienze Biochimiche “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Roma, ItalyDipartimento Scienze Biochimiche “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Roma, ItalyENEA CR Frascati, Diagnostics and Metrology Laboratory FSN-TECFIS-DIM, 00044 Frascati, ItalyDipartimento Scienze Biochimiche “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Roma, ItalyDipartimento di Farmacia e Biotecnologie (FaBiT), University of Bologna, 40126 Bologna, ItalyDipartimento di Farmacia e Biotecnologie (FaBiT), University of Bologna, 40126 Bologna, ItalyDipartimento Scienze Biochimiche “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Roma, ItalyLarge scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this review we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. The result of our analysis shows that a combination of experimental data on protein stability and in silico pathogenicity predictions allowed the identification of a subset of variants with a high probability of having a deleterious phenotypic effect, as confirmed by the significant enrichment of the subset in variants annotated in the COSMIC database as putative cancer-driving variants. Our analysis suggests that the integration of experimental and computational approaches may contribute to evaluate the risk for complex disorders and develop more effective treatment strategies.https://www.mdpi.com/1422-0067/22/11/5416protein structureprotein stabilityprotein functionsingle amino acid variantputative cancer driving variantfree-energy change |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Petrosino Leonore Novak Alessandra Pasquo Roberta Chiaraluce Paola Turina Emidio Capriotti Valerio Consalvi |
spellingShingle |
Maria Petrosino Leonore Novak Alessandra Pasquo Roberta Chiaraluce Paola Turina Emidio Capriotti Valerio Consalvi Analysis and Interpretation of the Impact of Missense Variants in Cancer International Journal of Molecular Sciences protein structure protein stability protein function single amino acid variant putative cancer driving variant free-energy change |
author_facet |
Maria Petrosino Leonore Novak Alessandra Pasquo Roberta Chiaraluce Paola Turina Emidio Capriotti Valerio Consalvi |
author_sort |
Maria Petrosino |
title |
Analysis and Interpretation of the Impact of Missense Variants in Cancer |
title_short |
Analysis and Interpretation of the Impact of Missense Variants in Cancer |
title_full |
Analysis and Interpretation of the Impact of Missense Variants in Cancer |
title_fullStr |
Analysis and Interpretation of the Impact of Missense Variants in Cancer |
title_full_unstemmed |
Analysis and Interpretation of the Impact of Missense Variants in Cancer |
title_sort |
analysis and interpretation of the impact of missense variants in cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-05-01 |
description |
Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this review we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. The result of our analysis shows that a combination of experimental data on protein stability and in silico pathogenicity predictions allowed the identification of a subset of variants with a high probability of having a deleterious phenotypic effect, as confirmed by the significant enrichment of the subset in variants annotated in the COSMIC database as putative cancer-driving variants. Our analysis suggests that the integration of experimental and computational approaches may contribute to evaluate the risk for complex disorders and develop more effective treatment strategies. |
topic |
protein structure protein stability protein function single amino acid variant putative cancer driving variant free-energy change |
url |
https://www.mdpi.com/1422-0067/22/11/5416 |
work_keys_str_mv |
AT mariapetrosino analysisandinterpretationoftheimpactofmissensevariantsincancer AT leonorenovak analysisandinterpretationoftheimpactofmissensevariantsincancer AT alessandrapasquo analysisandinterpretationoftheimpactofmissensevariantsincancer AT robertachiaraluce analysisandinterpretationoftheimpactofmissensevariantsincancer AT paolaturina analysisandinterpretationoftheimpactofmissensevariantsincancer AT emidiocapriotti analysisandinterpretationoftheimpactofmissensevariantsincancer AT valerioconsalvi analysisandinterpretationoftheimpactofmissensevariantsincancer |
_version_ |
1721414235049689088 |