CellPie: a scalable spatial transcriptomics factor discovery method via joint non-negative matrix factorization.

Spatially resolved transcriptomics has enabled the study of expression of genes within tissues while retaining their spatial identity. Most spatial transcriptomics (ST) technologies generate a matched histopathological image as part of the standard pipeline, providing morphological information that can complement the transcriptomics data. Here, we present CellPie, a fast, unsupervised factor discovery method based on joint non-negative matrix factorization of spatial RNA transcripts and histological image features. CellPie employs the accelerated hierarchical least squares method to significantly reduce the computational time, enabling efficient application to high-dimensional ST datasets. We assessed CellPie on three different human cancer types with different spatial resolutions, including a highly resolved Visium HD dataset, demonstrating both good performance and high computational efficiency compared to existing methods.