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Fig. 4 | Genome Medicine

Fig. 4

From: Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data

Fig. 4

Beyondcell characterises single-cell variability in drug response in cancer patients. a Using the Jerby-Arnon dataset [19], we were able to recapitulate the melanoma cells’ resistance to immune checkpoint inhibitors (ICI) at single-cell resolution. Left: therapeutic SSC clusters, each cell is coloured according to the cluster it belongs to. Centre: UMAP representing Beyondcell’s predicted affinity to the functional ICI resistance signature. Higher scores indicate a higher concordance between a cell transcriptome and the signature. Right: A violin plot of the normalised ICI resistance score by therapeutic cluster. b Beyondcell proposes alvocidib as a therapeutic alternative to ICI cells. Left: UMAP of alvocidib drug score (SSC collection), where higher scores indicate cells whose transcriptome is concordant with alvocidib sensitivity. Right: A scatterplot of alvocidib drug score and ICI resistance score. Alvocidib sensitivity positively correlates with immune resistance (R = 0.61, p < 0.01). c Beyondcell recapitulates the heterogeneous response of SCLC patients [5]. Top right: UMAP plot of the patient’s distribution after obtaining Beyondcell’s therapeutic clusters. Top centre: Beyondcell’s detected therapeutic clusters. The UMAP shows how the TCs were primarily driven by the patient/CDX origin regardless of response to platinum. Top right: UMAP coloured by the predicted sensitivity status of the patients. Bottom: summary of Beyondcell’s proposed drugs to target platinum-resistant cells (further details are available in Additional file 13: Table S12)

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