Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses
DOI10.5281/zenodo.8177571Zenodo8177571MaRDI QIDQ6693701
Dataset published at Zenodo repository.
Author name not available (Why is that?)
Publication date: 24 July 2023
Copyright license: No records found.
Patient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling, DNA-damage, cell-cycle activity, and apoptosis in 2,500 colorectal cancer (CRC) PDOs and cancer associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developed Trellis a highly-scalable, hierarchical tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is rare, patient-specific, and aligns with cancer cell PTM signaling. We find that CAFs can regulate cancer cell plasticity shifting proliferative stem cells to slow-cycling revival stem cells via YAP to protect cancer cells from chemotherapy. This repo contains the processed scRNA-seq Scanpy AnnData objects generated from the study. More information describing the data can be found at: https://github.com/TAPE-Lab/Ramos-et-al-Trellis
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