We introduce a simple integrated analysis method that links cellular phenotypic behaviour with single-cell RNA sequencing (scRNA-seq) by utilizing a combination of optical indices from cells and hydrogel beads. With our method, the combinations, referred to as joint colour codes, enable the link via matching the optical combinations measured by conventional epi-fluorescence microscopy with the concatenated DNA molecular barcodes created by cell-hydrogel bead pairs and sequenced by next-generation sequencing. We validated our approach by demonstrating an accurate link between the cell image and scRNA-seq with mixed species experiments, longitudinal cell tagging by electroporation and lipofection, and gene expression analysis. Furthermore, we extended our approach to multiplexed chemical transcriptomics, which enabled us to identify distinct phenotypic behaviours in HeLa cells treated with various concentrations of paclitaxel, and determine the corresponding gene regulation associated with the formation of a multipolar spindle.

中文翻译：

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光组合索引通过连接细胞图像和转录组来实现高内容转录组学

我们引入了一种简单的集成分析方法，通过结合细胞和水凝胶珠的光学指数，将细胞表型行为与单细胞 RNA 测序 (scRNA-seq) 联系起来。通过我们的方法，这些组合（称为联合颜色代码）通过将传统落射荧光显微镜测量的光学组合与由细胞-水凝胶珠对创建并通过下一代测序测序的串联DNA分子条形码相匹配来实现链接。我们通过混合物种实验、电穿孔和脂转染纵向细胞标记以及基因表达分析来证明细胞图像和 scRNA-seq 之间的准确联系，从而验证了我们的方法。此外，我们将我们的方法扩展到多重化学转录组学，这使我们能够识别用不同浓度的紫杉醇处理的 HeLa 细胞中的不同表型行为，并确定与多极纺锤体形成相关的相应基因调控。