Crecerelle - Processed datasets and trained models

This Zenodo archive contains the processed datasets and trained models to reproduce all results in the manuscript "Deep generative embeddings of gene expression and splicing reposition the interpretation of single-cell transcriptomic signatures". The source code, analyses workflows, and notebooks are available at github.com/Hollfelder-Lab/crecerelle and we provide a documentation website at hollfelder-lab.github.io/crecerelle/. If you use processed datasets, intermediate analyses, scripts, notebooks, or models trained in your work, please cite the paper. Abstract Single-cell transcriptomic analysis predominantly derives cell identity from gene expression analysis, while alternative splicing is processed separately despite its fundamental role for cell homeostasis. To overcome the limits of separate investigations, we developed a probabilistic deep learning framework, Crecerelle, enabling resolution of the contributions of gene expression and alternative splicing in each cell. Crecerelle learns cell embeddings from gene expressions and alternative splicing isoforms, to decipher their mutually dependent impact on the functional characterisation of cells in a data-driven manner, exemplified for the Tabula Muris dataset. This is enabled through a zero-and-N-inflated Dirichlet-Multinomial for a variational autoencoder that learns cell embeddings solely from splicing profiles, as well as a bi-modal variational autoencoder with a relevance-weighted mixture-of-experts variational posterior to consolidate the modality-specific contribution at single-cell level. Crecerelle reveals cell-type-specific isoform markers as well as subpopulations with unique isoforms and uncovers regulatory and disease-associated pathways not detected by gene expression analyses alone. This scalable and interpretable framework thus allows a more holistic study of transcriptomic regulation and will open a route to modality-relevance-weighted investigations across single-cell multiomics datasets and their influence on cellular homeostasis, tissue development and disease phenotypes.