2. Academic Validation
  3. Deep representation learning of chemical-induced transcriptional profile for phenotype-based drug discovery

Deep representation learning of chemical-induced transcriptional profile for phenotype-based drug discovery

  • Nat Commun. 2024 Jun 25;15(1):5378. doi: 10.1038/s41467-024-49620-3.
Xiaochu Tong 1 2,  Ning Qu 1 2,  Xiangtai Kong 1 2,  Shengkun Ni 1 2,  Jingyi Zhou 1 3 4,  Kun Wang 1 5,  Lehan Zhang 1 2,  Yiming Wen 1 2 6,  Jiangshan Shi 1 2,  Sulin Zhang 7 8,  Xutong Li 9 10,  Mingyue Zheng 11 12 13
Affiliations

Affiliations

  • 1 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.
  • 2 University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
  • 3 School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
  • 4 Lingang Laboratory, Shanghai, 200031, China.
  • 5 School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
  • 6 School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
  • 7 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China. slzhang@simm.ac.cn.
  • 8 University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. slzhang@simm.ac.cn.
  • 9 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China. lixutong@simm.ac.cn.
  • 10 University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. lixutong@simm.ac.cn.
  • 11 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China. myzheng@simm.ac.cn.
  • 12 University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. myzheng@simm.ac.cn.
  • 13 School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. myzheng@simm.ac.cn.
PMID: 38918369 DOI: 10.1038/s41467-024-49620-3
Abstract

Artificial intelligence transforms drug discovery, with phenotype-based approaches emerging as a promising alternative to target-based methods, overcoming limitations like lack of well-defined targets. While chemical-induced transcriptional profiles offer a comprehensive view of drug mechanisms, inherent noise often obscures the true signal, hindering their potential for meaningful insights. Here, we highlight the development of TranSiGen, a deep generative model employing self-supervised representation learning. TranSiGen analyzes basal cell gene expression and molecular structures to reconstruct chemical-induced transcriptional profiles with high accuracy. By capturing both cellular and compound information, TranSiGen-derived representations demonstrate efficacy in diverse downstream tasks like ligand-based virtual screening, drug response prediction, and phenotype-based drug repurposing. Notably, in vitro validation of TranSiGen's application in pancreatic Cancer drug discovery highlights its potential for identifying effective compounds. We envisage that integrating TranSiGen into the drug discovery and mechanism research holds significant promise for advancing biomedicine.

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