Spatial Transcriptomics in Breast Cancer Reveals Tumour Microenvironment-Driven Drug Responses and Clonal Therapeutic Heterogeneity

We acquired 10x Visium spatial transcriptomics (ST) data from 9 patients with invasive adenocarcinomas [1–5] to explore the role of the tumour microenvironment (TME) on intratumor heterogeneity (ITH) and drug response in breast cancer. By leveraging a new version of Beyondcell [6] (cnio-bu/beyondcell), a tool for identifying tumour cell subpopulations with distinct drug response patterns, we predicted sensitivity to over 1,200 drugs while accounting for the spatial context and interaction between the tumour and TME compartments. Moreover, we also used Beyondcell to compute spot-wise functional enrichment scores and identify niche-specific biological functions. Here, you can find: In signatures folder: SSc breast: Collection of gene signatures used to predict sensitivity to > 1,200 drugs derived from breast cancer cell lines. Functional signatures: Collection of gene signatures used to compute enrichment in different biological pathways. In visium folder: Visium objects: Processed ST Seurat objects with deconvoluted spots, SCTransform-normalised counts, and clonal composition predicted with SCEVAN [7]. These objects, together with the signatures, were used to compute the Beyondcell objects. In single-cell folder: Single-cell objects: Raw and filtered merged single-cell RNA-seq (scRNA-seq) Seurat objects with unnormalised counts used as a reference for spot deconvolution. In beyondcell folder: Beyondcell sensitivity objects with prediction scores for all drug response signatures in SSc breast. Beyondcell functional objects with enrichment scores for all functional signatures.