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. 2021 Dec 16;13:187. doi: 10.1186/s13073-021-01001-x

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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 SS_C 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 (SS_C 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)