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. 2020 May 14;11:2393. doi: 10.1038/s41467-020-16212-w

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© The Author(s) 2020

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Normalized mRNA expression for the indicated genes, previously associated with chemotherapy or targeted therapy resistance, in erALK-TKI cell lines across the indicated functional categories. b UMAP analysis of single-cell mRNA expression data from cells exposed to 0.5 μM alectinib for the indicated time duration. c Violin plot of expression levels of ALK and HER2 following indicated duration of exposure to the indicated ALK-TKIs. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 of a Mann–Whitney U-test. d ALK-TKI sensitivity of engineered cell lines, lentivirally overexpressing indicated genes to the indicated ALK-TKIs (0.5 μM), as determined by Cell Titer Glo assay. Mean ± SD of experimental replicates (n = 6, representing separate wells) are shown. e Impact of combination of individual resistance mechanisms toward sensitivity to indicated ALK-TKIs (0.5 μM), determined by Cell Titer Glo assay. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 of ANOVA analysis with Dunnett’s (d) or Tukey’s (e) multiple comparison correction. Mean ± SD of experimental replicates (n = 6, representing separate wells) are shown.