High-throughput chemical screens typically use coarse assays such as cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here, we introduce "sci-Plex," which uses "nuclear hashing" to quantify global transcriptional responses to thousands of independent perturbations at single-cell resolution. As a proof of concept, we applied sci-Plex to screen three cancer cell lines exposed to 188 compounds. In total, we profiled ~650,000 single-cell transcriptomes across ~5000 independent samples in one experiment. Our results reveal substantial intercellular heterogeneity in response to specific compounds, commonalities in response to families of compounds, and insight into differential properties within families. In particular, our results with histone deacetylase inhibitors support the view that chromatin acts as an important reservoir of acetate in cancer cells.

中文翻译：

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以单细胞分辨率大规模多路复用化学转录组学。

高通量化学筛选通常使用诸如细胞存活之类的粗略测定法，限制了可以了解的作用机理，脱靶效应和异质反应的知识。在这里，我们介绍“ sci-Plex”，它使用“核哈希”来量化在单细胞分辨率下对数千个独立扰动的全局转录反应。作为概念的证明，我们应用了sci-Plex来筛选暴露于188种化合物的三种癌细胞系。总共，我们在一个实验中对〜5000个独立样本中的〜650,000个单细胞转录组进行了分析。我们的结果表明，对特定化合物的反应具有实质性的细胞间异质性，对化合物家族的响应具有共同性，并且洞悉了家族中的不同特性。特别是，