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. 2022 Feb 23;603(7899):166–173. doi: 10.1038/s41586-022-04437-2

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© The Author(s) 2022

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. 3 — a, Volcano plot of biomarkers associated with ΔIC₅₀ (n = 2,006,328). Statistically significant large effect-size biomarkers (n = 884) are coloured by analysis type. Examples discussed in the text and selected outliers are labelled. Exp., expression; mut., mutant. b, Schematic of MAPK pathway showing the relationship between NRAS and BRAF. Low expression of NRAS is a biomarker of certain dabrafenib-containing combinations. c, Network of interactors of PIK3CA, showing its position two nodes away from targets of MK-2206 and linsitinib. PIK3CA mutation is predictive of the linsitinib + MK-2206 combination response in the KRAS-mutant molecular context. d, Number of combinations with at least three synergistic cell lines and combination response biomarkers (ΔE_max or ΔIC₅₀). e, Gain of ERBB2 is associated with sapitinib + JQ1 combination response in breast and all synergistic cell lines have an ERBB2 amplification. f, KRAS mutation is associated with trametinib + MK-2206 combination response in a pan-tissue setting (left, two-sided Welch’s t-test) and most synergistic cell lines harbour mutated KRAS (right). In box plots, the horizontal line shows the median, boxes extend across first and third quartiles, and whiskers extend to 1.5× interquartile range.