论文标题

非背带步行步行揭示了稀疏染色质相互作用网络中的隔室

Non-backtracking walks reveal compartments in sparse chromatin interaction networks

论文作者

Polovnikov, K., Gorsky, A., Nechaev, S., Razin, S. V., Ulianov, S.

论文摘要

通过蛋白质机械稳定的染色质群落在基因调节和染色质纤维的全球聚合物折叠中起着重要作用。但是,在经典网络理论的框架(随机块模型,SBM)的框架中对这些社区的处理未考虑染色质基因蛋白基因座的固有线性连通性。在这里,我们提出了“聚合物”模型模型,为聚合物网络中的社区检测铺平了道路。在此新模型的基础上,我们修改了非背带流动运算符,并提出了第一个用于稀疏单细胞HI-C矩阵中隔室域注释的协议。特别是,我们证明我们的方法对应于最大熵原理。基准分析表明,聚合物非背带操作员的光谱将真正的隔室结构解析为理论可检测性阈值,而所有常用的操作员都超过了它。我们在真实数据上测试了各种运算符,并得出结论,非折线单细胞域的大小最接近总体数据中的隔室尺寸。此外,发现的结构域在基因密度上显然分离并与种群隔室面膜相关,从而证实了我们对单个细胞中染色质腔域的注释的生物学意义。

Chromatin communities stabilized by protein machinery play essential role in gene regulation and refine global polymeric folding of the chromatin fiber. However, treatment of these communities in the framework of the classical network theory (stochastic block model, SBM) does not take into account intrinsic linear connectivity of the chromatin loci. Here we propose the "polymer" block model, paving the way for community detection in polymer networks. On the basis of this new model we modify the non-backtracking flow operator and suggest the first protocol for annotation of compartmental domains in sparse single cell Hi-C matrices. In particular, we prove that our approach corresponds to the maximum entropy principle. The benchmark analyses demonstrates that the spectrum of the polymer non-backtracking operator resolves the true compartmental structure up to the theoretical detectability threshold, while all commonly used operators fail above it. We test various operators on real data and conclude that the sizes of the non-backtracking single cell domains are most close to the sizes of compartments from the population data. Moreover, the found domains clearly segregate in the gene density and correlate with the population compartmental mask, corroborating biological significance of our annotation of the chromatin compartmental domains in single cells Hi-C matrices.

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