MOTIVATION: We introduce a statistical approach for pattern recognition in multivariate spatial transcriptomics data. RESULTS: Our algorithm constructs a projection of the data onto a low-dimensional feature space which is optimal in maximizing Moran's I, a measure of spatial dependency. This projection mitigates non-spatial variation and outperforms principal components analysis for pre-processing. Patterns of spatially variable genes are well represented in this feature space, and their projection can be shown to be a denoising operation. Our framework does not require any parameter tuning, and it furthermore gives rise to a calibrated, powerful test of spatial gene expression. AVAILABILITY AND IMPLEMENTATION: The algorithm is implemented in the open source software R and is available at https://github.com/IMSBCompBio/SpaCo.

The eukaryotic mRNA life cycle includes transcription, nuclear mRNA export and degradation. To quantify all these processes simultaneously, we perform thiol-linked alkylation after metabolic labeling of RNA with 4-thiouridine (4sU), followed by sequencing of RNA (SLAM-seq) in the nuclear and cytosolic compartments of human cancer cells. We develop a model that reliably quantifies mRNA-specific synthesis, nuclear export, and nuclear and cytosolic degradation rates on a genome-wide scale. We find that nuclear degradation of polyadenylated mRNA is negligible and nuclear mRNA export is slow, while cytosolic mRNA degradation is comparatively fast. Consequently, an mRNA molecule generally spends most of its life in the nucleus. We also observe large differences in the nuclear export rates of different 3'UTR transcript isoforms. Furthermore, we identify genes whose expression is abruptly induced upon metabolic labeling. These transcripts are exported substantially faster than average mRNAs, suggesting the existence of alternative export pathways. Our results highlight nuclear mRNA export as a limiting factor in mRNA metabolism and gene regulation.