Background Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking. Results Here, we described a novel computational framework, SAPAS, that utilizes 3′-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3′ UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern of Pak3 could classify chandelier cells into different subpopulations that are from different laminar positions. Conclusions We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity.

Groundwater is a pivotal resource for many human populations and ecosystems. However, in groundwater sciences (hydrogeology), there remain many challenges in understanding key processes; including groundwater origins, water fluxes, and controls on water quality. The stable isotopes of water are naturally occurring, form part of the water molecule, can be measured at high spatial and temporal resolutions and have predictable fractionations that may be used to understand key water cycle processes. Such qualities mean that stable isotopes are a key tracer in defining the spatial and temporal heterogeneity of groundwater systems. This article provides an overview of the use of stable isotopes to analyze (i) groundwater recharge from both rainfall and irrigation water, and presents case studies that highlight the use of stable isotopes to determine the frequency, rapidity, and origins of recharge; (ii) groundwater flow pathways including paleo‐groundwater and mixing processes, and case studies of deeply circulating mineral waters, groundwater mixing, and origins of paleo‐groundwater; (iii) groundwater discharge via evaporation, surface waters, and case studies that highlight the modeling of dynamic tropical river inflows and submarine groundwater discharge; and (iv) groundwater salinity, including a comparison of processes driving salinization in two regional groundwater basins.

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