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Unveiling new interdependencies between significant DNA methylation sites, gene expression profiles and glioma patients survival
Polish Acad Sci, Inst Comp Sci, Warsaw, Poland..
Polish Acad Sci, Inst Comp Sci, Warsaw, Poland..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.ORCID iD: 0000-0002-4922-8415
Nencki Inst Expt Biol, Warsaw, Poland..
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2018 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 4390Article in journal (Refereed) Published
Abstract [en]

In order to find clinically useful prognostic markers for glioma patients' survival, we employed Monte Carlo Feature Selection and Interdependencies Discovery (MCFS-ID) algorithm on DNA methylation (HumanMethylation450 platform) and RNA-seq datasets from The Cancer Genome Atlas (TCGA) for 88 patients observed until death. The input features were ranked according to their importance in predicting patients' longer (400+ days) or shorter (<= 400 days) survival without prior classification of the patients. Interestingly, out of the 65 most important features found, 63 are methylation sites, and only two mRNAs. Moreover, 61 out of the 63 methylation sites are among those detected by the 450 k array technology, while being absent in the HumanMethylation27. The most important methylation feature (cg15072976) overlaps with the RE1 Silencing Transcription Factor (REST) binding site, and was confirmed to intersect with the REST binding motif in human U87 glioma cells. Six additional methylation sites from the top 63 overlap with REST sites. We found that the methylation status of the cg15072976 site affects transcription factor binding in U87 cells in gel shift assay. The cg15072976 methylation status discriminates <= 400 and 400+ patients in an independent dataset from TCGA and shows positive association with survival time as evidenced by Kaplan-Meier plots.

Place, publisher, year, edition, pages
2018. Vol. 8, article id 4390
National Category
Cancer and Oncology Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-350614DOI: 10.1038/s41598-018-22829-1ISI: 000427237200001PubMedID: 29535343OAI: oai:DiVA.org:uu-350614DiVA, id: diva2:1209469
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AstraZenecaAvailable from: 2018-05-23 Created: 2018-05-23 Last updated: 2022-09-15Bibliographically approved

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Diamanti, KlevKomorowski, Jan

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