A Multi-Phenotype System to Discover Therapies for Age-Related Dysregulation of the Immune Response to Viral Infections

Abstract

Age-related immune dysregulation contributes to increased susceptibility to infection and disease in older adults. We combined high-throughput laboratory automation with machine learning to build a multi-phenotype aging profile that models the dysfunctional immune response to viral infection in older adults. From a single well, our multi-phenotype aging profile can capture changes in cell composition, physical cell-to-cell interaction, organelle structure, cytokines, and other hidden complexities contributing to age-related dysfunction. This system allows for rapid identification of new potential compounds to rejuvenate older adults’ immune response. We used our technology to screen thousands of compounds for their ability to make old immune cells respond to viral infection like young immune cells. We observed beneficial effects of multiple compounds, of which two of the most promising were disulfiram and triptonide. Our findings indicate that disulfiram could be considered as a treatment for severe coronavirus disease 2019 and other inflammatory infections.

Morphological single-cell analysis of peripheral blood mononuclear cells from 390 healthy blood donors with Blood Cell Painting

“…Thus far, Cell Painting has been primarily applied to cancer cell lines and human fibroblasts (Bray et al 2016, Willis et al 2020, with human immune cells receiving less attention. Nevertheless, morphological profiling with Cell Painting has been used to study immune responses in PBMCs of older adults after viral infection (White, 2020).…”

Cell-Vision Fusion: A Swin Transformer-based Approach to Predicting Kinase Inhibitor Mechanism of Action from Cell Painting Data

“…Deep learning-based approaches have proved successful in many biological domains, from the classification of radiographic and pathological images 26,27 to industrial-level drug discovery 11 . They have also recently been applied in the context of image-base profiling to develop phenotypic models of active SARS-CoV-2 infection 28 and in the identification of new potential compounds to rejuvenate the immune systems of elderly adults 29 .…”