DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2–5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Background and Purpose-The purpose of this study was to compare recanalization and reperfusion in terms of their predictive value for imaging outcomes (follow-up infarct volume, infarct growth, salvaged penumbra) and clinical outcome in acute ischemic stroke patients. Material and Methods-Twenty-two patients admitted within 6 hours of stroke onset were retrospectively included in this study. These patients underwent a first stroke CT protocol including CT-angiography (CTA) and perfusion-CT (PCT) on admission, and similar imaging after treatment, typically around 24 hours, to assess recanalization and reperfusion. Recanalization was assessed by comparing arterial patency on admission and posttreatment CTAs; reperfusion, by comparing the volumes of CBV, CBF, and MTT abnormality on admission and posttreatment PCTs. Collateral flow was graded on the admission CTA. Follow-up infarct volume was measured on the discharge noncontrast CT. The groups of patients with reperfusion, no reperfusion, recanalization, and no recanalization were compared in terms of imaging and clinical outcomes. Results-Reperfusion (using an MTT reperfusion index Ͼ75%) was a more accurate predictor of follow-up infarct volume than recanalization. Collateral flow and recanalization were not accurate predictors of follow-up infarct volume. An interaction term was found between reperfusion and the volume of the admission penumbra Ͼ50 mL. Conclusion-Our study provides evidence that reperfusion is a more accurate predictor of follow-up infarct volume in acute ischemic stroke patients than recanalization. We recommend an MTT reperfusion index Ͼ75% to assess therapy efficacy in future acute ischemic stroke trials that use perfusion-CT. (Stroke. 2010;41:e34-e40.)

BACKGROUND AND PURPOSE: SHT and ME are feared complications in patients with acute ischemic stroke. They occur Ͼ10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke.