Generation of synthetic whole-slide image tiles of tumours from RNA-sequencing data via cascaded diffusion models.

Training machine-learning models with synthetically generated data can alleviate the problem of data scarcity when acquiring diverse and sufficiently large datasets is costly and challenging. Here we show that cascaded diffusion models can be used to synthesize realistic whole-slide image tiles from latent representations of RNA-sequencing data from human tumours. Alterations in gene expression affected the composition of cell types in the generated synthetic image tiles, which accurately preserved the distribution of cell types and maintained the cell fraction observed in bulk RNA-sequencing data, as we show for lung adenocarcinoma, kidney renal papillary cell carcinoma, cervical squamous cell carcinoma, colon adenocarcinoma and glioblastoma. Machine-learning models pretrained with the generated synthetic data performed better than models trained from scratch. Synthetic data may accelerate the development of machine-learning models in scarce-data settings and allow for the imputation of missing data modalities.