Immense amount of high-content image data generated in drug discovery screening requires computationally driven automated analysis. Emergence of advanced machine learning algorithms, like deep learning models, has transformed the interpretation and analysis of imaging data. However, deep learning methods generally require large number of high-quality data samples, which could be limited during preclinical investigations. To address this issue, we propose a generative modeling based computational framework to synthesize images, which can be used for phenotypic profiling of perturbations induced by drug compounds. We investigated the use of three variants of Generative Adversarial Network (GAN) in our framework, viz., a basic Vanilla GAN, Deep Convolutional GAN (DCGAN) and Progressive GAN (ProGAN), and found DCGAN to be most efficient in generating realistic synthetic images. A pre-trained convolutional neural network (CNN) was used to extract features of both real and synthetic images, followed by a classification model trained on real and synthetic images. The quality of synthesized images was evaluated by comparing their feature distributions with that of real images. The DCGAN-based framework was applied to high-content image data from a drug screen to synthesize high-quality cellular images, which were used to augment the real image data. The augmented dataset was shown to yield better classification performance compared with that obtained using only real images. We also demonstrated the application of proposed method on the generation of bacterial images and computed feature distributions for bacterial images specific to different drug treatments. In summary, our results showed that the proposed DCGAN-based framework can be utilized to generate realistic synthetic high-content images, thus enabling the study of drug-induced effects on cells and bacteria.
Keywords: Deep learning; Drug discovery; Generative modeling; High-content imaging.
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