We applied this approach to compare the Roadmap Epigenomics reference epigenomes with the 16 ENCODE 2012 samples with broad mark coverage (Extended Data 6). We found that H3K4me1 signal in enhancer chromatin states correctly groups primary cells from similar tissues across the two projects, emphasizing the robustness of our annotations and signal tracks across projects (Extended Data 6a). For example, epidermal keratinocytes NHEK group with other keratinocytes, mammary epithelial cells HMEC with other skin cells, and skeletal muscle myoblasts HSMM and osteoblasts with bone marrow. Some cancer cell lines also grouped with corresponding primary tissues, including hepatocellular carcinoma HepG2 with liver tissue, primary lung fibroblasts NHLF with the IMR90 lung fibroblast cell line, and T cell leukemia Dnd41 with Thymus, while in other cases cancerous cell lines grouped together, e.g. HeLa-S3 cervical carcinoma with A549 lung carcinoma. Similarly, H3K27me3 signal in Polycomb-repressed states grouped five immortalized cell lines together (Extended Data 6c), despite their T-cell, Lung, Cervical, Leukemia, and Hepatocellular origins12,64. This larger trees spanning ENCODE 2012 and Roadmap Epigenomics also highlighted the large number of lineages not previously covered by reference epigenomes, including brain, muscle, smooth muscle, heart, mucosa, digestive tract, and fetal tissues.
