singIST: an R/Bioconductor library and Quarto dashboard for automated single-cell comparative transcriptomics analysis ofdisease models and humans

Abstract

Preclinical disease models often diverge from human pathophysiology at single-cell resolution, complicating model selection and limiting translational value. We present singIST, an R/Bioconductor package for quantitative and explainable comparison of disease model scRNA-seq data against a human reference. For each superpathway, singIST fits an adaptive sparse multi-block PLS-DA model on human pseudobulk expression, integrated one-to-one orthology and cell type mapping, and translates model fold changes into the human expression space to compute signed recapitulation at the superpathway, cell type, and gene levels. To streamline interpretation and reporting, we provide singIST Visualizer, a companion Quarto/Shiny dashboard that loads singIST outputs and offers interactive exploration with export ready plots and tables, avoiding manual figure coding across many superpathways and models. We demonstrate the workflow. We illustrate an end-to-end workflow on an oxazolone mouse model against a human atopic dermatitis reference for two representative pathways: Dendritic Cells in regulating Th1/Th2 Development [BIOCARTA] and Cytokine-cytokine receptor interaction [KEGG]. singIST is distributed under the MIT License via Bioconductor, and the Visualizer is available on GitHub.