Journal: Pediatric diabetes

Article Title: DNA Methylation and its Role in the Pathogenesis of Diabetes

doi: 10.1111/pedi.12521

Figure Lengend Snippet: Genome Wide DNA Methylation Assays.

Article Snippet: Various studies have mapped genome wide DNA methylation using the Infinium 450k bead array or MeDIP in placentae from women with GDM and have found increased number of differentially methylated genes predominantly involved in glucose metabolism pathway and in energy metabolism ( 80 – 83 ).

Techniques: Genome Wide, DNA Methylation Assay, Methylation, Next-Generation Sequencing

Journal: Briefings in Bioinformatics

Article Title: Refinement of computational identification of somatic copy number alterations using DNA methylation microarrays illustrated in cancers of unknown primary

doi: 10.1093/bib/bbac161

Figure Lengend Snippet: Computational prediction of SCNA from DNA methylation arrays using conumee- K CN . ( A ) Workflow for the developed strategy to refine SCNA detection, ‘conumee- K CN ’, trained over 442 primary tumor samples from TCGA, across 18 cancer types, with matched genotyping (SNP6 array) and DNA methylation array (450K) data. Our thresholding strategy refines conumee outputs and quantitatively calls SCNA from 450K arrays by considering tumor purity ρ (RF_Purity) and rigorous estimation of copy-number-state ( CN )-dependent constants K CN . * A list of 94 genes frequently amplified or deleted in cancer was used as reference to define the copy number states. Thus, by using calibrated K CN ’s and considering tumor purity, intra-sample variability and copy-number-state-dependent noise, thresholds for each CN can be estimated for each 450K profiled sample to accurately identify SCNA. ( B ) Benchmarking of our strategy (conumee- K CN ) against conumee (fixed threshold of 0.3), cnAnalysis450k and ChAMP in an independent, validation set consisting of 151 TCGA samples, with matched genotyping (SNP6 array) and DNA methylation array (450K) data. True positive (TP) and false-positive (FP) rates of 450K-derived calls versus SNP6-derived calls (ASCAT) for amplifications are depicted, showing the improved performance of our approach. ( C ) TP and FP rates of conumee- K CN versus ASCAT in the TCGA validation set for the three amplification copy number states (Amp10, Amp and Gain). ( D ) Representative examples of gene amplifications in two samples from the TCGA validation cohort. Thresholds estimated by conumee- K CN for Amp and Amp10 are depicted (dotted grey lines). TP = #𝑇𝑟u𝑒 p𝑜𝑠𝑖𝑡𝑖v𝑒𝑠/#𝑇𝑟u𝑒 p𝑜𝑠𝑖𝑡𝑖v𝑒𝑠 + #𝐹𝑎l𝑠𝑒 𝑁𝑒g𝑎𝑡𝑖v𝑒𝑠; FP = #𝐹𝑎l𝑠𝑒 p𝑜𝑠𝑖𝑡𝑖v𝑒𝑠/#𝐹𝑎l𝑠𝑒 p𝑜𝑠𝑖𝑡𝑖v𝑒𝑠 + #𝑇𝑟u𝑒 𝑁𝑒g𝑎𝑡𝑖v𝑒𝑠.

Article Snippet: In recent years, as a potential alternative to the use of SNP-based SNP Array 6.0 (SNP6) arrays, several approaches to detect genome-wide Somatic Copy Number Alterations (SCNAs) from Infinium Human Methylation 450K/EPIC arrays have been developed [ ] and are applied in several fields, including cancer research [i.e. ].

Techniques: DNA Methylation Assay, Amplification, Biomarker Discovery, Derivative Assay