论文标题

机器学习RNA结构预测的模型

Machine learning a model for RNA structure prediction

论文作者

Calonaci, Nicola, Jones, Alisha, Cuturello, Francesca, Sattler, Michael, Bussi, Giovanni

论文摘要

RNA功能至关重要地取决于其结构。当前用于二级结构预测的热力学模型依赖于计算折叠合奏的分区功能,因此可以估计最小的自由能结构和集成种群。除非辅助实验数据补充,否则这些模型有时无法识别天然结构。在这里,我们构建了一组模型,该模型通过一个网络通过向集合自由能扰动的网络组合了热力学参数,化学探测数据(DMS,Shape)和共进化数据(直接耦合分析,DCA,DCA)。训练扰动以增加一组已知天然RNA结构的代表性集合。在网络的化学探测节点中,一个卷积窗口结合了相邻的反应率,启发了它们的结构信息含量和局部构型合奏的贡献。正则化用于限制过度拟合和提高可传递性。最容易转移的模型是通过交叉验证策略选择的,该策略估算了模型在未经训练的系统上的性能。通过所选模型,我们在独立验证集中获得了增加天然结构的集合种群,并获得了更准确的预测。该方法的灵活性使模型可以轻松地重新训练并进行调整以纳入任意实验信息。

RNA function crucially depends on its structure. Thermodynamic models currently used for secondary structure prediction rely on computing the partition function of folding ensembles, and can thus estimate minimum free-energy structures and ensemble populations. These models sometimes fail in identifying native structures unless complemented by auxiliary experimental data. Here, we build a set of models that combine thermodynamic parameters, chemical probing data (DMS, SHAPE), and co-evolutionary data (Direct Coupling Analysis, DCA) through a network that outputs perturbations to the ensemble free energy. Perturbations are trained to increase the ensemble populations of a representative set of known native RNA structures. In the chemical probing nodes of the network, a convolutional window combines neighboring reactivities, enlightening their structural information content and the contribution of local conformational ensembles. Regularization is used to limit overfitting and improve transferability. The most transferable model is selected through a cross-validation strategy that estimates the performance of models on systems on which they are not trained. With the selected model we obtain increased ensemble populations for native structures and more accurate predictions in an independent validation set. The flexibility of the approach allows the model to be easily retrained and adapted to incorporate arbitrary experimental information.

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