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發表期刊：Nature Methods

發表時間：2025

Abstract:

In this Resource, we present an extensive dataset of chemical-induced gene signatures (CIGS), encompassing expression patterns of 3,407 genes regulating key biological processes in 2 human cell lines exposed to 13,221 compounds across 93,664 perturbations. This dataset encompasses 319,045,108 gene expression events, generated through 2 high-throughput technologies: the previously documented high-throughput sequencing-based high-throughput screening (HTS2) and the newly developed highly multiplexed and parallel sequencing (HiMAP-seq). Our results show that HiMAP-seq is comparable to RNA sequencing, but can profile the expression of thousands of genes across thousands of samples in one single test by utilizing a pooled-sample strategy. We further illustrate CIGS’s utility in elucidating the mechanism of action of unannotated small molecules, like ligustroflavone and 2,4-dihydroxybenzaldehyde, and to identify perturbation-induced cell states, such as those resistant to ferroptosis.

https://doi.org/10.1038/s41592-025-02781-5