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. 2019 Jul 23;38(38):6491–6506. doi: 10.1038/s41388-019-0895-2

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© The Author(s) 2019

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. 1 — a Multi-gene oncodriver hypothesis. b Analysis workflow. c Network showing functionally related protein families with members in common Reactome pathways (nodes) displaying significantly enriched, mutually exclusive mutated positions (edges) pan-cancer. Node diameter is proportional to the total number of nonsynonymous mutations (number of unique samples) for a family member; thicker cyan borders indicate families where at least one highly conserved position is significantly mutated. Inside each node, mutated members of a given family are displayed, with a diameter proportional to the number of mutations. Edge thickness is proportional to average shortest paths between the two families