RT Journal Article
SR Electronic
T1 Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.14.200600
DO 10.1101/2020.07.14.200600
A1 Alma Andersson
A1 Ludvig Larsson
A1 Linnea Stenbeck
A1 Fredrik Salmén
A1 Anna Ehinger
A1 Sunny Wu
A1 Ghamdan Al-Eryani
A1 Daniel Roden
A1 Alex Swarbrick
A1 Åke Borg
A1 Jonas Frisén
A1 Camilla Engblom
A1 Joakim Lundeberg
YR 2020
UL http://biorxiv.org/content/early/2020/07/14/2020.07.14.200600.abstract
AB In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra-and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.Competing Interest StatementJ. F., and J. L., are scientific consultants for 10X Genomics Inc., providing spatially barcoded slides.