PRESCRIBE: Predicting Single-Cell Responses with Bayesian Estimation

In single-cell perturbation prediction, a central task is to forecast the effects of perturbing a gene unseen in the training data. The efficacy of such predictions depends on two factors: (1) the similarity of the target gene to those covered in the training data, which informs model (epistemic) uncertainty, and (2) the quality of the corresponding training data, which reflects data (aleatoric) uncertainty. Both factors are critical for determining the reliability of a prediction, particularly as gene perturbation is an inherently stochastic biochemical process. In this paper, we propose PRESCRIBE (PREdicting Single-Cell Response wIth Bayesian Estimation), a multivariate deep evidential regression framework designed to measure both sources of uncertainty jointly. Our analysis demonstrates that PRESCRIBE effectively estimates a confidence score for each prediction, which strongly correlates with its empirical accuracy. This capability enables the filtering of untrustworthy results, and in our experiments, it achieves steady accuracy improvements of over 3% compared to comparable baselines.

MIRACLE: Multi-task Learning based Interpretable Regulation of Autoimmune Diseases through Common Latent Epigenetics

DNA methylation is a crucial regulator of gene transcription and has been linked to various diseases, including autoimmune diseases and cancers. However, diagnostics based on DNA methylation face challenges due to large feature sets and small sample sizes, resulting in overfitting and suboptimal performance. To address these issues, we propose MIRACLE, a novel interpretable neural network that leverages autoencoder-based multi-task learning to integrate multiple datasets and jointly identify common patterns in DNA methylation. MIRACLE's architecture reflects the relationships between methylation sites, genes, and pathways, ensuring biological interpretability and meaningfulness. The network comprises an encoder and a decoder, with a bottleneck layer representing pathway information as the basic unit of heredity. Customized defined MaskedLinear Layer is constrained by site-gene-pathway graph adjacency matrix information, which provides explainability and expresses the site-gene-pathway hierarchical structure explicitly. And from the embedding, there are different multi-task classifiers to predict diseases. Tested on six datasets, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, psoriasis, and type 1 diabetes, MIRACLE demonstrates robust performance in identifying common functions of DNA methylation across different phenotypes, with higher accuracy in prediction dieseases than baseline methods. By incorporating biological prior knowledge, MIRACLE offers a meaningful and interpretable framework for DNA methylation data analysis in the context of autoimmune diseases.