Latent variable models are powerful statistical tools that can uncover relevant variation between patients or cells, by inferring unobserved hidden states from observable high-dimensional data. A major shortcoming of current methods, however, is their inability to learn sparse and interpretable hidden states. Additionally, in settings where partial knowledge on the latent structure of the data is readily available, a statistically sound integration of prior information into current methods is challenging. To address these issues, we propose spex-LVM, a factorial latent variable model with sparse priors to encourage the inference of explainable factors driven by domain-relevant information. spex-LVM utilizes existing knowledge of curated biomedical pathways to automatically assign annotated attributes to latent factors, yielding interpretable results tailored to the corresponding domain of interest. Evaluations on simulated and real single-cell RNA-seq datasets demonstrate that our model robustly identifies relevant structure in an inherently explainable manner, distinguishes technical noise from sources of biomedical variation, and provides dataset-specific adaptations of existing pathway annotations. Implementation is available at https://github.com/MLO-lab/spexlvm.
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