Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.
Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.
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DOI：
10.1016/j.sbi.2015.11.002
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发表时间：
2015-12
影响因子：
6.8
通讯作者：
Ozkan SB
中科院分区：
文献类型：
--
作者：
Kumar A;Butler BM;Kumar S;Ozkan SB
测序技术揭示了每个人外显子组中许多新的非同义单核苷酸变体（nsSNV）。为了评估它们的功能影响，比较基因组学经常被用来预测它们是否是良性的。然而，仅仅进化分析是不够的，因为它误诊了许多疾病相关的nsSNV，如那些在蛋白质界面参与的位置，因为进化预测不提供机制的见解功能的变化或损失。结构分析可以通过在nSNV诊断中结合构象动力学和变构来帮助克服这两个问题。最后，蛋白质-蛋白质相互作用网络使用系统水平的方法阐明了疾病的病因和发病机制。将这些网络方法与结构解析的蛋白质相互作用和动力学联系起来，将推动基因组医学的发展。
Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.