The rapid accumulation of single-cell chromatin accessibility data offers a unique opportunity to investigate common and specific regulatory mechanisms across different cell types. However, existing methods for cis-regulatory network reconstruction using single-cell chromatin accessibility data were only designed for cells belonging to one cell type, and resulting networks may be incomparable directly due to diverse cell numbers of different cell types. Here, we adopt a computational method to jointly reconstruct cis-regulatory interaction maps (JRIM) of multiple cell populations based on patterns of co-accessibility in single-cell data. We applied JRIM to explore common and specific regulatory interactions across multiple tissues from single-cell ATAC-seq dataset containing ~80 000 cells across 13 mouse tissues. Reconstructed common interactions among 13 tissues indeed relate to basic biological functions, and individual cis-regulatory networks show strong tissue specificity and functional relevance. More importantly, tissue-specific regulatory interactions are mediated by coordination of histone modifications and tissue-related TFs, and many of them may reveal novel regulatory mechanisms.

中文翻译：

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使用单细胞染色质可及性数据联合重建跨多个组织的顺式调节相互作用网络。

单细胞染色质可及性数据的快速积累为研究不同细胞类型的常见和特定调节机制提供了独特的机会。然而，现有的使用单细胞染色质可及性数据重建顺式调控网络的方法仅适用于属于一种细胞类型的细胞，由于不同细胞类型的细胞数量不同，所产生的网络可能直接无法比较。在这里，我们采用一种计算方法来联合重建顺式-基于单细胞数据中可共同访问模式的多个细胞群的调节相互作用图（JRIM）。我们应用 JRIM 来探索来自单细胞 ATAC-seq 数据集（包含 13 个小鼠组织的约 80 000 个细胞）的多个组织之间的常见和特定调节相互作用。重建的 13 种组织之间的共同相互作用确实与基本生物功能有关，并且个体顺式调节网络显示出很强的组织特异性和功能相关性。更重要的是，组织特异性调节相互作用是由组蛋白修饰和组织相关 TF 的协调介导的，其中许多可能揭示新的调节机制。