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

Analysis and interpretation of the impact of missense variants in cancer / Petrosino, M.; Novak, L.; Pasquo, A.; Chiaraluce, R.; Turina, P.; Capriotti, E.; Consalvi, V. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 11:22(2021). [10.3390/ijms22115416]

Analysis and interpretation of the impact of missense variants in cancer

Petrosino, M.;Novak, L.;Chiaraluce, R.
;
Capriotti, E.
;
Consalvi, V
2021

Abstract

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
2021
protein structure; protein stability; protein function; single amino acid variant; putative cancer driving variant; free-energy change
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Analysis and interpretation of the impact of missense variants in cancer / Petrosino, M.; Novak, L.; Pasquo, A.; Chiaraluce, R.; Turina, P.; Capriotti, E.; Consalvi, V. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 11:22(2021). [10.3390/ijms22115416]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1548711
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