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. [email protected].
  • 9. Yibin Vocational College of Medicine and Health, Yibin, China. [email protected].
  • 10. Iomics Biosciences Inc., Beijing, China. [email protected].
  • 11. School of Basic Medical Sciences, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China. [email protected].
  • # 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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