Deep learning enhanced deciphering of brain activity maps for discovery of therapeutics for brain disorders.

Journal: iScience
Published Date: Jun 10, 2025

Abstract

This study presents an artificial intelligence enhanced screening platform, DeepBAM, which enables deep learning of large-scale whole brain activity maps (BAMs) from living, drug-responsive larval zebrafish for neuropharmacological prediction. Automated microfluidics and high-speed microscopy are utilized to achieve high-throughput phenotypic screening for generating the BAM library. Deep learning is applied to deconvolve the pharmacological information from the BAM library and to predict the therapeutical potential of non-clinical compounds without any prior information about the chemicals. For a validation set composed of blinded clinical neuro-drugs, several potent anti-Parkinson's disease and anti-epileptic drugs are predicted with nearly 45% accuracy. The prediction capability of DeepBAM is further tested with a set of nonclinical compounds, revealing the pharmaceutical potential in 80% of the anti-epileptic and 36% of the anti-Parkinson predictions. These data support the notion of systems-level phenotyping in combination with machine learning to aid therapeutics discovery for brain disorders.

Authors

  • Xianrui Zhang
    Peng Cheng Laboratory, Shenzhen, 518066, China. Electronic address: zhangxr01@pcl.ac.cn.
  • Zhen Liu
    School of Pharmacy, Fudan University, PR China; Analytical Service Unit, WuXi AppTec (Shanghai) Co., Ltd, Shanghai, 200131, PR China.
  • Xuan Luo
    Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China.
  • Yi Cao
    Department of Dermatology, First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • Wencong Zhang
    Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR 999077, China.
  • Honglin Li
    Innovation Center for AI and Drug Discovery, East China Normal University, China.
  • Wei Li
    Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • Shuk Han Cheng
    Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong SAR 999077, China.
  • Stephen J Haggarty
    Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, 02114, USA. shaggarty@mgh.harvard.edu.
  • Xin Wang
    Key Laboratory of Bio-based Material Science & Technology (Northeast Forestry University), Ministry of Education, Harbin 150040, China.
  • Peng Shi

Keywords

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