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. 2019 Dec 12;9:18937. doi: 10.1038/s41598-019-55454-7

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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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Signaling circuits analyzed in the diabetes case study. Nodes in orange contain genes whose LoF causes an upregulation of the circuit and nodes in blue contain genes whose inactivation causes circuit downregulation. (A) Rap1 signaling pathway:PRKCI PARD6A PARD3, (B) Chemokynes pathway:PARD3-PRKCZ-TIAM1 and (C) TNF signaling pathway:CREB3 circuits.