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. 2018 Jul 31;8:11474. doi: 10.1038/s41598-018-29847-z

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© The Author(s) 2018

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/.

PMC Copyright notice

The network of clock-immune related genes (NCIRG) connects elements of the circadian clock network and the immune system. An enrichment analysis on immune-related GO terms and KEEG pathways of the NCRG, and manual curation based on published data of immune-related genes with interactions with the CCN added a set (35) of immune-related genes (dark blue) to the network. Orange, light green and light purple elements represent the core-clock network (CCN, 20 elements), the extended core-clock network (ECCN) and the network of clock-related genes (NCRG), respectively. Grey lines represent the connection between genes previously published in the NCRG; green and red lines refer to positive and negative (respectively) interactions between newly added immune-related genes and the CCN, based on published data. Black arrows indicate the direction of each interaction. Dashed lines mark the interactions found in modified in vitro/in vivo models. It is important to notice that in some of the studies used for the construction of the network double KD or KO animals/cells were used. In such cases, it was not possible to specify the exact gene responsible for the reported effect on the immune genes, CRY, PER, ROR and REV-ERB were used to refer to the gene family. The direction of the effect is represented by an arrow for activation and a dead end arrow for the inhibition pointing to the affected gene.