Giotto, a toolbox for integrative analysis and visualization of spatial expression data

The rapid development of novel spatial transcriptomic and proteomic technologies has provided new opportunities to investigate the interactions between cells and their native microenvironment. However, effective use of such technologies requires the development of innovative computational tools that are easily accessible and intuitive to use. Here we present Giotto, a comprehensive, flexible, robust, and open-source toolbox for spatial transcriptomic and proteomic data analysis and visualization. The data analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing cell-type distribution, spatially coherent gene expression patterns, and interactions between each cell and its surrounding neighbors. Furthermore, Giotto can also be used in conjunction with external single-cell RNAseq data to infer the spatial enrichment of cell types from data that do not have single-cell resolution. The data visualization module allows users to interactively visualize the gene expression data, analysis outputs, and additional imaging features, thereby providing a user-friendly workspace to explore multiple modalities of information for biological investigation. These two modules can be used iteratively for refined analysis and hypothesis development. We applied Giotto to a wide range of public datasets encompassing diverse technologies and platforms, thereby demonstrating its general applicability for spatial transcriptomic and proteomic data analysis and visualization.