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. 2023 Jan 23;13:1247. doi: 10.1038/s41598-023-28259-y

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© The Author(s) 2023

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 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/.

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Function-based, minimally connected first order protein:protein interaction networks of the top endotype specific DE genes. (a) NPS endotype network. (b) INF endotype network. The top 200 endotype-specific DE genes (by absolute value fold changes) were input into NetworkAnalyst⁵⁴. Each DE gene set formed a well-connected minimum connected first-order network, indicating that the genes involved are functionally related and likely collectively regulate or play key roles in one or more related biological mechanisms. Red and green nodes are genes with increased and decreased expression specific to the endotype, respectively, while grey nodes are interconnecting first-order interaction nodes. The size of the nodes indicates their connectivity (hub degree) within the network, i.e., how well interconnected any given node is to other nodes in the Network (NB. hubs are key molecules in signalling since they are highly interconnected; they receive and integrate multiple signals and pass them on to downstream nodes). Lines represent edges that indicate known (experimentally-determined) protein:protein interactions derived from www.innatedb.ca (version 5.4).