Abstract
Pan-cancer study can uncover cell- and tissue-specific genomic loci and regions with underlying biological functions, as one of fundamental procedures toward precision medicine. We utilized the online curated resource of DNA methylation annotation knowledgebase, to implement the cross-cell interrogation of pan-cancer study of breast cancer. The study revealed genome-wide differentially-methylated loci and regions by the reduced representation bisulfite sequencing profiling. The knowledgebase contains three level of curated information across multiple cancer and normal cells from the ENCODE Consortium. The reference base covers all identified differentially-methylation CpG sites and regions of interest, further annotated gene information, together with tumor suppressor gene and methylation level. Lastly, it includes the inferred functional association network and related Gene Ontology analysis results based on all the tumor suppressor genes identified from the differentially-methylated regions of interest. Our knowledgebase and analysis results provide a thorough reference source for biomedical researchers and clinicians. The cross-cell analysis results are deposited at: http://github.com/gladex/DMAK.
Highlights
Pan-cancer study can uncover most of cell- and tissuespecific genomic loci and regions with underlying biological functions (Kristensen et al, 2014; Leiserson et al, 2015; The Cancer Genome Atlas Research Network et al, 2013; Witte et al, 2014)
To biomedical researchers and clinicians, there is no systematic reference source of functional association between DNA methylation and transcriptional regulation for wet-lab experiment design and post-experiment validation. This is an imperative for most biologists and biomedical researchers to improve their research outcomes and efficiency (Bock and Lengauer, 2008; Roadmap Epigenomics Consortium et al, 2015)
The third level analysis mainly includes the visualization and function analysis for the annotated results, which include the functional association network for tumor suppressor genes identified from the hyper- or hypo-differentially-methylated regions (DMR) detected from the above analysis
Summary
Pan-cancer study can uncover most of cell- and tissuespecific genomic loci and regions with underlying biological functions (Kristensen et al, 2014; Leiserson et al, 2015; The Cancer Genome Atlas Research Network et al, 2013; Witte et al, 2014). We utilized our online curated reference source for DNA Methylation Annotation Knowledgebase (DMAK) and implemented the cross-cell analysis in pan -cancer study.
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