High-throughput profiling of chemical-induced gene expression across 93,644 perturbations

Nat Methods. 2025 Aug 18. doi: 10.1038/s41592-025-02781-5.

Lei Xiang ^# ¹, Yumei Wang ^# ¹, Wei Shao ^# ² ³, Qingzhou Li ⁴, Xiankuo Yu ¹, Mingming Wei ¹, Yu Gui ⁴, Shengrong Li ⁴, Pan Qin ¹, Chao Hu ¹, Guochen Zhang ¹, Xianwen Zhang ¹, Jiawen Wang ², Yingying Li ², Jun An ¹, Yan Luo ¹, Yile Liao ¹, Jinghong Deng ¹, Xinran Tai ¹, Richard Y Xu ⁵, Lijun Huang ¹, Dale Guo ⁴, Guanbin Zhang ⁶, Zhi Xie ⁷, Yun Deng ⁸ ⁹, Junquan Xu ¹⁰, Dong Wang ¹¹

Affiliations

1 School of Basic Medical Sciences, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
2 Iomics Biosciences Inc., Beijing, China.
3 Chinese Institutes for Medical Research, Beijing, China.
4 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
5 Department of Biology, University of California, San Diego, La Jolla, CA, USA.
6 School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
7 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
8 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. dengyun@cdutcm.edu.cn.
9 Yibin Vocational College of Medicine and Health, Yibin, China. dengyun@cdutcm.edu.cn.
10 Iomics Biosciences Inc., Beijing, China. jqxu@iomicsbio.com.
11 School of Basic Medical Sciences, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China. dwang@cdutcm.edu.cn.
# Contributed equally.

PMID: 40826206 DOI: 10.1038/s41592-025-02781-5

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. The full dataset is publicly accessible at https://cigs.iomicscloud.com/ .

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