Analysis and Interpretation of the Impact of Missense Variants in Cancer.
Analysis and Interpretation of the Impact of Missense Variants in Cancer.
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DOI：
10.3390/ijms22115416
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发表时间：
2021-05-21
影响因子：
5.6
通讯作者：
Consalvi V
中科院分区：
文献类型：
--
作者：
Petrosino M;Novak L;Pasquo A;Chiaraluce R;Turina P;Capriotti E;Consalvi V
大规模基因组测序可以识别大量的遗传变异，其对人类健康的影响仍然未知。在这篇综述中，我们分析，在硅为基础的战略，错义变异对癌症相关基因的影响，其对蛋白质的稳定性和功能的影响是实验确定的。我们从11种蛋白质中收集了一组164种变体，以分析错义突变在结构和功能水平上的影响，并评估最先进的方法（FoldX和Meta-SNP）用于预测蛋白质稳定性变化和致病性的性能。我们的分析结果表明，蛋白质稳定性和计算机致病性预测的实验数据的组合允许鉴定具有高概率具有有害表型效应的变体子集，如通过在COSMIC数据库中注释为推定的癌症驱动变体的变体子集的显著富集所证实的。我们的分析表明，实验和计算方法的整合可能有助于评估复杂疾病的风险，并制定更有效的治疗策略。
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.
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影响因子：
14.9
作者：
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