PT - JOURNAL ARTICLE AU - Reuben Moncada AU - Florian Wagner AU - Marta Chiodin AU - Joseph C. Devlin AU - Maayan Baron AU - Cristina H. Hajdu AU - Diane M. Simeone AU - Itai Yanai TI - Building a tumor atlas: integrating single-cell RNA-Seq data with spatial transcriptomics in pancreatic ductal adenocarcinoma AID - 10.1101/254375 DP - 2018 Jan 01 TA - bioRxiv PG - 254375 4099 - http://biorxiv.org/content/early/2018/03/05/254375.short 4100 - http://biorxiv.org/content/early/2018/03/05/254375.full AB - To understand tissue architecture it is necessary to understand both which cell types are present and their physical relationships to one another. Single-cell RNA-Seq (scRNA-Seq) has made significant progress towards the unbiased and systematic characterization of cell populations within a tissue by studying hundreds and thousands of cells in a single experiment. However, the characterization of the spatial organization of individual cells within a tissue has been more elusive. The recently introduced ‘spatial transcriptomics’ method (ST) reveals the spatial pattern of gene expression within a tissue section at a resolution of a thousand 100 μm spots across the tissue, each capturing the transcriptomes of ∼10−20 cells. Here, we present an approach for the integration of scRNA-Seq and ST data generated from the same sample of pancreatic cancer tissue. Using markers for cell types identified by scRNA-Seq, we robustly deconvolved the cell type composition of each ST spot to generate a spatial atlas of cell proportions across the tissue. Studying this atlas, we found that distinct spatial localizations accompany each of the cell populations that we identified. Our results provide a framework for creating a tumor atlas by mapping single-cell populations to their spatial region, as well as the inference of cell architecture in any tissue.