VIB Center for Brain & Disease Research, Leuven, Belgium.
Department of Human Genetics, KU Leuven, Leuven, Belgium.
Nat Methods. 2023 Sep;20(9):1355-1367. doi: 10.1038/s41592-023-01938-4. Epub 2023 Jul 13.
Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven gene regulatory networks (GRNs). Here we present a method for the inference of enhancer-driven GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TFs) and links these enhancers to candidate target genes. To improve both recall and precision of TF identification, we curated and clustered a motif collection with more than 30,000 motifs. We benchmarked SCENIC+ on diverse datasets from different species, including human peripheral blood mononuclear cells, ENCODE cell lines, melanoma cell states and Drosophila retinal development. Next, we exploit SCENIC+ predictions to study conserved TFs, enhancers and GRNs between human and mouse cell types in the cerebral cortex. Finally, we use SCENIC+ to study the dynamics of gene regulation along differentiation trajectories and the effect of TF perturbations on cell state. SCENIC+ is available at scenicplus.readthedocs.io .
在单个细胞中对染色质可及性和基因表达进行联合分析，为破译增强子驱动的基因调控网络（GRN）提供了机会。在这里，我们提出了一种称为 SCENIC+的增强子驱动的 GRN 推断方法。SCENIC+ 预测基因组增强子以及候选上游转录因子（TF），并将这些增强子与候选靶基因联系起来。为了提高 TF 识别的召回率和精度，我们整理并聚类了一个包含超过 30000 个基序的 motif 集合。我们在来自不同物种的不同数据集上对 SCENIC+进行了基准测试，包括人外周血单核细胞、ENCODE 细胞系、黑色素瘤细胞状态和果蝇视网膜发育。接下来，我们利用 SCENIC+的预测来研究大脑皮层中人类和小鼠细胞类型之间保守的 TF、增强子和 GRN。最后，我们使用 SCENIC+研究沿着分化轨迹的基因调控动态以及 TF 扰动对细胞状态的影响。SCENIC+可在 scenicplus.readthedocs.io 上获得。
