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. 2021 Dec 16;13:189. doi: 10.1186/s13073-021-01000-y

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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 — Prioritizing drug combinations targeting transcriptionally-distinct subclones with CaDRReS-Sc. a Proportions of various transcriptionally distinct cell clusters (n=21) in head and neck cancer patient-derived cell lines. b Heatmap of predicted cell death percentages across cell clusters within each patient. c Comparison between predicted and observed drug response for five different drug combinations and patient-derived cells. Boxplots contrasting monotherapy (gray) and combinatorial therapy (orange) response based on d CaDRReS-Sc predictions and e experimental measurements. Error bars show 1 standard deviation (n=2–3), dashed lines indicate the best monotherapy, and asterisk symbols indicate drug combinations that show improvement. In general, relative response values for monotherapy and combinatorial therapy, as observed from experimental measurements, were also reflected in CaDRReS-Sc predictions. f Boxplots showing that drug combinations that were observed to improve over monotherapy (x-axis, no/low vs high determined based on median value in experiment) had significantly higher predicted improvements (combination over monotherapy) using CaDRReS-Sc as well (y-axis)