Predicting stability of DNA bulge at mononucleotide microsatellite.
Predicting stability of DNA bulge at mononucleotide microsatellite.
复制标题
预测单核苷酸微卫星DNA凸起的稳定性。
DOI：
10.1093/nar/gkab616
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发表时间：
2021-08-20
影响因子：
14.9
通讯作者：
Zhang DY
中科院分区：
文献类型：
--
作者：
Bae JH;Zhang DY
单核苷酸微卫星是临床和法医学上至关重要的DNA序列，因为它们在人类基因组中具有高度的突变性和丰度。作为微卫星中Indel的诱变中间体和这种诱变后的探针杂交的结果，在微卫星内形成具有结构简并滑动的凸起。然而，尽管这种动态突起在癌症基因组学和神经疾病研究中起着关键作用，但人们对其稳定性仍知之甚少。在这篇文章中，我们建立了一个模型，它预测了微小卫星上滑动凸起的热力学。我们首先确定了可以组装成任何滑动凸起的40个常见的凸起状态，然后用脚趾交换能量测量和配分函数对它们进行了表征。我们的模型首次预测了三次以上重复的滑动凸起的自由能，可以推断任意序列和长度的滑动凸起的稳定性惩罚，预测误差的中位数为0.22千卡/摩尔。预测的模式清楚地解释了文献中观察到的微卫星的情况，例如较长的微卫星和C/G微卫星的较高突变率。
Mononucleotide microsatellites are clinically and forensically crucial DNA sequences due to their high mutability and abundance in the human genome. As a mutagenic intermediate of an indel in a microsatellite and a consequence of probe hybridization after such mutagenesis, a bulge with structural degeneracy sliding within a microsatellite is formed. Stability of such dynamic bulges, however, is still poorly understood despite their critical role in cancer genomics and neurological disease studies. In this paper, we have built a model that predicts the thermodynamics of a sliding bulge at a microsatellite. We first identified 40 common bulge states that can be assembled into any sliding bulges, and then characterized them with toehold exchange energy measurement and the partition function. Our model, which is the first to predict the free energy of sliding bulges with more than three repeats, can infer the stability penalty of a sliding bulge of any sequence and length with a median prediction error of 0.22 kcal/mol. Patterns from the prediction clearly explain landscapes of microsatellites observed in the literature, such as higher mutation rates of longer microsatellites and C/G microsatellites.
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