Morphological profiling for drug discovery in the era of deep learning.

Journal: Briefings in bioinformatics
Published Date:

Abstract

Morphological profiling is a valuable tool in phenotypic drug discovery. The advent of high-throughput automated imaging has enabled the capturing of a wide range of morphological features of cells or organisms in response to perturbations at the single-cell resolution. Concurrently, significant advances in machine learning and deep learning, especially in computer vision, have led to substantial improvements in analyzing large-scale high-content images at high throughput. These efforts have facilitated understanding of compound mechanism of action, drug repurposing, characterization of cell morphodynamics under perturbation, and ultimately contributing to the development of novel therapeutics. In this review, we provide a comprehensive overview of the recent advances in the field of morphological profiling. We summarize the image profiling analysis workflow, survey a broad spectrum of analysis strategies encompassing feature engineering- and deep learning-based approaches, and introduce publicly available benchmark datasets. We place a particular emphasis on the application of deep learning in this pipeline, covering cell segmentation, image representation learning, and multimodal learning. Additionally, we illuminate the application of morphological profiling in phenotypic drug discovery and highlight potential challenges and opportunities in this field.

Authors

  • Qiaosi Tang
    Calico Life Sciences, South San Francisco, CA 94080, United States.
  • Ranjala Ratnayake
    Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 32610, United States.
  • Gustavo Seabra
    Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 32610, United States.
  • Zhe Jiang
    Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
  • Ruogu Fang
    J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL.
  • Lina Cui
    Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 32610, United States.
  • Yousong Ding
    Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 32610, United States.
  • Tamer Kahveci
    Department of Computer & Information Science & Engineering, University of Florida, Gainesville, FL 32611, United States.
  • Jiang Bian
    Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Chenglong Li
    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing Laboratory for Food Quality and Safety, Beijing, 100193, People's Republic of China.
  • Hendrik Luesch
    Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL 32610, United States.
  • Yanjun Li
    NSF Center for Big Learning, University of Florida, Gainesville, FL.