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. 2015 Jan 8;11(1):e1004005. doi: 10.1371/journal.pcbi.1004005

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© 2015 Mahoney et al

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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The consensus genes for the inflammatory and fibroproliferative subsets are connected in the IMP functional network. Inflammatory genes are colored purple, while fibroproliferative genes are colored red. Genes with polymorphisms are colored in green and MRSS biomarker genes are colored yellow. One MRSS biomarker gene (IFI44) was also an inflammatory consensus gene (pink), while three polymorphic genes were inflammatory consensus genes (turquoise). Note the five distinct subnetworks corresponding to type I interferons, M2 macrophages, ECM proteins and TGFβ signaling, adaptive immunity, and cell proliferation. The interferon, M2 macrophage, and adaptive immunity subnetworks are composed almost exclusively of inflammatory genes, while the ECM subnetwork shares genes from both intrinsic subsets. Furthermore, the polymorphic genes interact primarily with inflammatory subset genes indicating that the genetic risk in SSc is related to immune abnormalities.