Supervised analysis of alternative polyadenylation from single-cell and spatial transcriptomics data with spvAPA.

Abstract

Alternative polyadenylation (APA) is an important driver of transcriptome diversity that generates messenger RNA isoforms with distinct 3' ends. The rapid development of single-cell and spatial transcriptomic technologies opened up new opportunities for exploring APA data to discover hidden cell subpopulations invisible in conventional gene expression analysis. However, conventional gene-level analysis tools are not fully applicable to APA data, and commonly used unsupervised dimensionality reduction methods often disregard experimentally derived annotations such as cell type identities. Here, we proposed a supervised analytical framework termed spvAPA, specifically used for APA analysis from both single-cell and spatial transcriptomics data. First, an iterative imputation method based on weighted nearest neighbor was designed to recover missing APA signatures, by integrating both gene expression and APA modalities. Second, a supervised feature selection method based on sparse partial least squares discriminant analysis was devised to identify APA features distinguishing cell types or spatial morphologies. Additionally, spvAPA improves the visualization of high-dimensional data for discovering novel cell subtypes, which considers APA features and dual modalities of gene expression and APA. Evaluations across nine single-cell and spatial transcriptomics datasets demonstrate the effectiveness and applicability of spvAPA. spvAPA is available at https://github.com/BMILAB/spvAPA.