论文标题
单链断裂位点的全基因组核苷酸分辨率模型揭示了物种进化层次结构
Genome-wide nucleotide-resolution model of single-strand break site reveals species evolutionary hierarchy
论文作者
论文摘要
储层计算是预测湍流的有力工具，其简单的架构具有处理大型系统的计算效率。然而，其实现通常需要完整的状态向量测量和系统非线性知识。我们使用非线性投影函数将系统测量扩展到高维空间，然后将其输入到储层中以获得预测。我们展示了这种储层计算网络在时空混沌系统上的应用，该系统模拟了湍流的若干特征。我们表明，使用径向基函数作为非线性投影器，即使只有部分观测并且不知道控制方程，也能稳健地捕捉复杂的系统非线性。最后，我们表明，当测量稀疏、不完整且带有噪声，甚至控制方程变得不准确时，我们的网络仍然可以产生相当准确的预测，从而为实际湍流系统的无模型预测铺平了道路。
Single-strand breaks (SSBs) are the major DNA damage in the genome arising spontaneously as the outcome of genotoxins and intermediates of DNA transactions. SSBs play a crucial role in various biological processes and show a non-random distribution in the genome. Several SSB detection approaches such as S1 END-seq and SSiNGLe-ILM emerged to characterize the genomic landscape of SSB with nucleotide resolution. However, these sequencing-based methods are costly and unfeasible for large-scale analysis of diverse species. Thus, we proposed the first computational approach, SSBlazer, which is an explainable and scalable deep learning framework for genome-wide nucleotide-resolution SSB site prediction. We demonstrated that SSBlazer can accurately predict SSB sites and sufficiently alleviate false positives by constructing an imbalanced dataset to simulate the realistic SSB distribution. The model interpretation analysis reveals that SSBlazer captures the pattern of individual CpG in genomic context and the motif of TGCC in the center region as critical features. Besides, SSBlazer is a lightweight model with robust cross-species generalization ability in the cross-species evaluation, which enables the large-scale genome-wide application in diverse species. Strikingly, the putative SSB genomic landscapes of 216 vertebrates reveal a negative correlation between SSB frequency and evolutionary hierarchy, suggesting that the genome tends to be integrity during evolution.
