Morphological Profiling for Drug Discovery in the Era of Deep Learning

TL;DR

This paper reviews recent advances in morphological profiling for drug discovery, emphasizing deep learning techniques for image analysis, and discusses datasets, applications, challenges, and future opportunities in the field.

Contribution

It provides a comprehensive overview of deep learning applications in morphological profiling, including workflows, strategies, datasets, and challenges in phenotypic drug discovery.

Findings

Deep learning improves cell segmentation and image representation.

Morphological profiling aids in understanding drug mechanisms and repurposing.

Public benchmark datasets facilitate research and development.

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 (MOA), 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.