Wisconsin Institute for Discovery, University of Wisconsin, Madison, Wisconsin 53715, USA.
Department of Computer Sciences, University of Wisconsin, Madison, Wisconsin 53715, USA.
Genome Res. 2022 Jul;32(7):1367-1384. doi: 10.1101/gr.276542.121. Epub 2022 Jun 15.
Changes in transcriptional regulatory networks can significantly alter cell fate. To gain insight into transcriptional dynamics, several studies have profiled bulk multi-omic data sets with parallel transcriptomic and epigenomic measurements at different stages of a developmental process. However, integrating these data to infer cell type-specific regulatory networks is a major challenge. We present dynamic regulatory module networks (DRMNs), a novel approach to infer cell type-specific -regulatory networks and their dynamics. DRMN integrates expression, chromatin state, and accessibility to predict -regulators of context-specific expression, where context can be cell type, developmental stage, or time point, and uses multitask learning to capture network dynamics across linearly and hierarchically related contexts. We applied DRMNs to study regulatory network dynamics in three developmental processes, each showing different temporal relationships and measuring a different combination of regulatory genomic data sets: cellular reprogramming, liver dedifferentiation, and forward differentiation. DRMN identified known and novel regulators driving cell type-specific expression patterns, showing its broad applicability to examine dynamics of gene regulatory networks from linearly and hierarchically related multi-omic data sets.
转录调控网络的变化可以显著改变细胞命运。为了深入了解转录动态,有几项研究对发育过程的不同阶段进行了平行的转录组学和表观基因组学测量,以描绘批量多组学数据集。然而,将这些数据整合起来以推断细胞类型特异性调控网络是一个主要挑战。我们提出了动态调控模块网络 (DRMN),这是一种推断细胞类型特异性调控网络及其动态的新方法。DRMN 集成了表达、染色质状态和可及性来预测特定于上下文的表达的调控因子,其中上下文可以是细胞类型、发育阶段或时间点,并使用多任务学习来捕获跨线性和层次相关上下文的网络动态。我们将 DRMN 应用于三个发育过程中的调控网络动态研究,每个过程都显示出不同的时间关系,并测量不同的调控基因组数据集组合:细胞重编程、肝去分化和正向分化。DRMN 确定了已知和新的调控因子,这些因子驱动细胞类型特异性表达模式,表明其广泛适用于检查来自线性和层次相关多组学数据集的基因调控网络的动态。