Towards the Next Generation of Data-Driven Therapeutics Using Spatially Resolved Single-Cell Technologies and Generative AI.

Recent advances in multi-omics and spatially resolved single-cell technologies have revolutionised our ability to profile millions of cellular states, offering unprecedented opportunities to understand the complex molecular landscapes of human tissues in both health and disease. These developments hold immense potential for precision medicine, particularly in the rational design of novel therapeutics for treating inflammatory and autoimmune diseases. However, the vast, high-dimensional data generated by these technologies present significant analytical challenges, such as distinguishing technical variation from biological variation or defining relevant questions that leverage the added spatial dimension to improve our understanding of tissue organisation. Generative artificial intelligence (AI), specifically variational autoencoder- or transformer-based latent variable models, provides a powerful and flexible approach to addressing these challenges. These models make inferences about a cell's intrinsic state by effectively identifying complex patterns, reducing data dimensionality and modelling the biological variability in single-cell datasets. This review explores the current landscape of single-cell and spatial multi-omics technologies, the application of generative AI in data analysis and modelling and their transformative impact on our understanding of autoimmune diseases. By combining spatial and single-cell data with advanced AI methodologies, we highlight novel insights into the pathogenesis of autoimmune disorders and outline future directions for leveraging these technologies to achieve the goal of AI-powered personalised medicine.