| 1. |
- Dabrowski, Michal J., et al.
(författare)
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Unveiling new interdependencies between significant DNA methylation sites, gene expression profiles and glioma patients survival
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Fallows, Richard A., et al.
(författare)
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A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
- 2020
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Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18-19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10-80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of similar to 20-40 ms(-1) with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of similar to 110 ms(-1) with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported.
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| 3. |
- Stepniak, Karolina, et al.
(författare)
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Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas. Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.
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