This study presents a comprehensive analysis of DNA methylation patterns across 30 diverse human cell and tissue types using 42 whole genome bisulfite sequencing (WGBS) datasets. The researchers identified 5.6 million dynamic CpGs, which are CpGs that change their methylation state during normal development. These dynamic CpGs are predominantly located distal to transcription start sites and co-localize with gene regulatory elements such as enhancers and transcription factor binding sites. The study also highlights the inefficiency of WGBS, as only a small fraction of sequencing reads provide relevant information about CpG methylation. The results show that DNA methylation patterns vary significantly across different cell types and tissues, with hESCs and their derivatives exhibiting the highest DNA methylation levels. In contrast, colon cancer and long-term cultured cell lines show global hypomethylation. The study also identifies differentially methylated regions (DMRs) that often harbor SNPs associated with cell type-related diseases. These DMRs are frequently found to overlap with transcription factor binding sites and enhancer-like regions, suggesting their potential regulatory roles. The study further demonstrates that a significant portion of DMRs overlap with known regulatory elements, including transcription factor binding sites. This suggests that these DMRs may serve as important regulatory elements in gene expression. The researchers also found that cell type-specific DMRs are enriched for transcription factors known to regulate the respective cellular states, highlighting the importance of these DMRs in cell identity and function. The study also compares DNA methylation changes in colon cancer and Alzheimer's disease samples to normal controls, identifying a large number of differentially methylated CpGs. The results suggest that the number of dynamic CpGs is significantly higher in developmental samples compared to long-term cultured cell lines. This indicates that the majority of CpGs that change their methylation state are involved in developmental processes. Finally, the study demonstrates the utility of the identified DMRs in classifying unknown samples and deconvoluting mixed samples. The results suggest that a representative subset of CpGs across a comprehensive set of DMRs can be used to accurately classify samples and infer regulatory events. The study concludes that while the number of dynamic CpGs may increase with more diverse cell types, the rate of newly discovered regulatory CpGs will drop rapidly once all major cell and tissue types have been mapped. This is due to the fact that tissue variability exceeds within-tissue variability by one order of magnitude.This study presents a comprehensive analysis of DNA methylation patterns across 30 diverse human cell and tissue types using 42 whole genome bisulfite sequencing (WGBS) datasets. The researchers identified 5.6 million dynamic CpGs, which are CpGs that change their methylation state during normal development. These dynamic CpGs are predominantly located distal to transcription start sites and co-localize with gene regulatory elements such as enhancers and transcription factor binding sites. The study also highlights the inefficiency of WGBS, as only a small fraction of sequencing reads provide relevant information about CpG methylation. The results show that DNA methylation patterns vary significantly across different cell types and tissues, with hESCs and their derivatives exhibiting the highest DNA methylation levels. In contrast, colon cancer and long-term cultured cell lines show global hypomethylation. The study also identifies differentially methylated regions (DMRs) that often harbor SNPs associated with cell type-related diseases. These DMRs are frequently found to overlap with transcription factor binding sites and enhancer-like regions, suggesting their potential regulatory roles. The study further demonstrates that a significant portion of DMRs overlap with known regulatory elements, including transcription factor binding sites. This suggests that these DMRs may serve as important regulatory elements in gene expression. The researchers also found that cell type-specific DMRs are enriched for transcription factors known to regulate the respective cellular states, highlighting the importance of these DMRs in cell identity and function. The study also compares DNA methylation changes in colon cancer and Alzheimer's disease samples to normal controls, identifying a large number of differentially methylated CpGs. The results suggest that the number of dynamic CpGs is significantly higher in developmental samples compared to long-term cultured cell lines. This indicates that the majority of CpGs that change their methylation state are involved in developmental processes. Finally, the study demonstrates the utility of the identified DMRs in classifying unknown samples and deconvoluting mixed samples. The results suggest that a representative subset of CpGs across a comprehensive set of DMRs can be used to accurately classify samples and infer regulatory events. The study concludes that while the number of dynamic CpGs may increase with more diverse cell types, the rate of newly discovered regulatory CpGs will drop rapidly once all major cell and tissue types have been mapped. This is due to the fact that tissue variability exceeds within-tissue variability by one order of magnitude.