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. 2017 May 4;7:1469. doi: 10.1038/s41598-017-01624-4

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© The Author(s) 2017

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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Integrative analysis of DNA methylome, transcriptome and functional enrichment data. (a) In the figure are the numbers of differentially expressed genes (GE), differentially methylated CpG sites (meCpG) and their overlap (both) between cisplatin sensitive and resistant cells (M019i) before cisplatin treatment (0 μM), and changes detected in response to drug treatment. The putative upstream regulators with gene expression changes and canonical pathway enrichments common for both DNA methylome and transcriptome data are shown in the (b) Gene expression changes, DNA methylation changes or both are shown for the known direct target genes of KLF4, in different comparisons as indicated by the color codes in (a). (c) Comparison of differences observed before cisplatin treatment and in response to 7 μM cisplatin treatment of resistant cells as indicated in the figure. *indicates the number of differentially methylated sites: in integrative comparisons, the number of overlapping genes closest to differentially methylated sites is shown. The functional analyses and networks in the figure were generated by using Ingenuity Pathway Analysis (IPA®, Qiagen).