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Of particular interest is our finding that multiple methylation patterns were represented within the TCGA Group 3 tumors such as MIA, DIRAS3, and GSTP1, loci with MP1 (SD-HypoB), MP2 (SI-HyperN), and MP4 (SD-DMinNB) patterns, respectively.
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The Illumina methylation array used in this study only targets 807 genes, of which we only considered the limited set of those with multiple CpGs exhibiting correlated methylation patterns.
Recently, microarray-based techniques provide a powerful tool to map methylation patterns in multiple genes and multiple CpG sites within genes [ 17, 18].
Although crypt methylation patterns from multiple different aged colons are consistent with a clock-like accumulation of epigenetic errors, environmental factors may also alter methylation.
Currently, efforts are being made to integrate different methylomes and to determine common and tissue-specific DNA methylation patterns across multiple tumor entities (pan-cancer).
Hu and colleagues [ 15] tested this hypothesis by analyzing the comprehensive DNA methylation patterns of multiple cell types from normal breast tissue, DCIS, and IDC using methylation-specific digital karyotyping.
Bisulfite treatment combined with Next-Generation sequencing (NGS) is the method of choice for the NIH Epigenomics Roadmap [ 5], a project with a stated goal to map methylation patterns in multiple tissue types.
As opposed to single-gene analysis, the integrated information on methylation patterns of multiple genes may reflect the functional status of several cellular pathways and prove to be a reliable predictor of prognosis.
In this study we report on genome-wide methylation patterns generated using multiple peripheral and internal tissues from two independent sets of donors using 450k methylation chips.
In a rat model, Ho and colleagues observed multiple changes in gene-specific DNA methylation patterns in the adult male prostate, including hypomethylation of the phosphodiesterase type 4 variant 4 (Pde4d4) [ 27].
Our results provide evidence in favor of multiple genomic processes underlying the DMR methylation patterns 1 to 3 observed across UC tumors, and implicate pattern 1 DMRs as infrequent sites of RF binding, pattern 2 DMRs as frequent sites of CTCF/RAD21 as well as EZH2 binding, and pattern 3 DMRs as sites of frequent POLR2A occupancy.
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