Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Genome Biol. 2022 Jan 6;23(1):8. doi: 10.1186/s13059-021-02593-8.
While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore this heterogeneity or use sorted cell populations, reducing discovery and explanatory power. Here, we develop scDALI, a versatile computational framework that integrates information on cellular states with allelic quantifications of single-cell sequencing data to characterize cell-state-specific genetic effects. We apply scDALI to scATAC-seq profiles from developing F1 Drosophila embryos and scRNA-seq from differentiating human iPSCs, uncovering heterogeneous genetic effects in specific lineages, developmental stages, or cell types.
虽然已经确定遗传变异的功能影响在细胞类型和状态上可能有所不同，但捕捉这种多样性仍然具有挑战性。目前使用批量测序的研究要么忽略了这种异质性，要么使用分选的细胞群体，从而降低了发现和解释的能力。在这里，我们开发了 scDALI，这是一个通用的计算框架，它将细胞状态的信息与单细胞测序数据的等位基因定量相结合，以描述细胞状态特异性的遗传效应。我们将 scDALI 应用于发育中的 F1 果蝇胚胎的 scATAC-seq 图谱和分化的人类 iPSC 的 scRNA-seq，揭示了特定谱系、发育阶段或细胞类型中的异质遗传效应。
