Motivation: scCRISPR-seq is an emerging high-throughput CRISPR screening technology that combines CRISPR screening with single-cell sequencing technologies. It provides rich information on the mechanism of gene regulation. However, when scCRISPR-seq is applied in a population of heterogeneous cells, the true cellular response to perturbation is coupled with infected proportion bias of guide RNAs (gRNAs) across different cell clusters. The mixing of these effects introduces noise into scCRISPR-seq data analysis and thus obstacles to relevant studies. Results: We developed scDecouple to decouple true cellular response of perturbation from the influence of infected proportion bias. scDecouple first models the distribution of gene expression profiles in perturbed cells and then iteratively finds the maximum likelihood of cell cluster proportions as well as the cellular response for each gRNA. We demonstrated its performance in a series of simulation experiments. By applying scDecouple to real scCRISPR-seq data, we found that scDecouple enhances the identification of biologically perturbation-related genes. scDecouple can benefit scCRISPR-seq data analysis, especially in the case of heterogeneous samples or complex gRNA libraries. Availability: scDecouple is freely available at https://github.com/MengQiuchen/scDecouple.

中文翻译：

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scDepair：将 scCRISPR-seq 中的细胞反应与感染比例偏差解耦

动机：scCRISPR-seq是一种新兴的高通量CRISPR筛选技术，它将CRISPR筛选与单细胞测序技术相结合。它提供了有关基因调控机制的丰富信息。然而，当 scCRISPR-seq 应用于异质细胞群时，细胞对扰动的真实反应与不同细胞簇中指导 RNA (gRNA) 的感染比例偏差相结合。这些效应的混合会给 scCRISPR-seq 数据分析带来噪音，从而给相关研究带来障碍。结果：我们开发了 scDe Couple 来将扰动的真实细胞反应与感染比例偏差的影响分开。scDepair 首先对受干扰细胞中基因表达谱的分布进行建模，然后迭代地找到细胞簇比例的最大似然以及每个 gRNA 的细胞反应。我们通过一系列模拟实验展示了其性能。通过将 scDepair 应用于真实的 scCRISPR-seq 数据，我们发现 scDepair 增强了生物扰动相关基因的识别。scDepair 有利于 scCRISPR-seq 数据分析，特别是在异质样品或复杂 gRNA 文库的情况下。可用性：scDe Couple 可在 https://github.com/MengQiuchen/scDe Couple 上免费获取。我们发现 scDepair 增强了生物扰动相关基因的识别。scDepair 有利于 scCRISPR-seq 数据分析，特别是在异质样品或复杂 gRNA 文库的情况下。可用性：scDe Couple 可在 https://github.com/MengQiuchen/scDe Couple 上免费获取。我们发现 scDepair 增强了生物扰动相关基因的识别。scDepair 有利于 scCRISPR-seq 数据分析，特别是在异质样品或复杂 gRNA 文库的情况下。可用性：scDe Couple 可在 https://github.com/MengQiuchen/scDe Couple 上免费获取。