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. 2020 Aug 24;10:14101. doi: 10.1038/s41598-020-70865-7

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© The Author(s) 2020

Open AccessThis 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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Increased hypoxia gene expression in CHB. Hypoxia upregulated gene signatures from Molecular Signatures Database were assessed in the CHB cohort, 19 significantly upregulated gene signatures identified (FDR < 0.05) and ranked by Normalized Enrichment Score (NES) (a). GSEA shows a significant enrichment of HepG2 defined hypoxic genes in CHB cohort (FDR = 0.077). The gene set was based on Fold Change > 2, and FDR < 0.05; 80 genes satisfied these criteria and are listed in Supplementary Table 2 (b). CHB cohort was grouped by peripheral ALT activity, with subjects > 40 IU/L (n = 57) or < 40 IU/L (n = 25). GSEA shows a significant enrichment of HepG2 defined hypoxic genes in patients with elevated ALT (FDR = 0.110) (c). HepG2 hypoxic gene set was enriched (FDR = 0.006) in HCV infected patients with cirrhosis (n = 41) compared to normal liver controls (n = 19) (d). MSigDB hallmark gene sets identified the most upregulated pathways in the CHB cohort: 28 gene sets were significantly enriched (FDR < 0.05) and are ranked by NES (e). All GSEA was performed using GSEA_4.0.3⁷¹.