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. 2019 Jul 24;9:10731. doi: 10.1038/s41598-019-46917-y

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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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Upstream regulatory analysis (URA) of differentially expressed genes (DEGs) predicted the estrogen receptor and beta-estradiol (P < 0.05) to be inhibited in HCV29 cells co-culture for 24 h with S. haematobium eggs. Panel A. Significantly upregulated genes are shown in red. These genes, negatively regulated (T-symbol) by the estrogen receptor, were found to be upregulated in HCV29 cells co-cultured with S. haematobium eggs for 24 hours; red dashed lines indicate that these genes were activated. Therefore, the URA analysis significantly predicted the estrogen receptor as an inhibited upstream regulator of this set of genes in this dataset. Panel B. Significantly downregulated genes are shown in green. These genes, positively regulated (arrow) by beta-estradiol, were found to be downregulated in HCV29 cells co-cultured with S. haematobium eggs for 24 hours; blue dashed lines indicate that these genes were inhibited in our dataset. Therefore, the URA analysis significantly predicted beta-estradiol as an inhibited upstream regulator of this set of genes in the dataset.