Project description:Ageing is the accumulation of changes and overall decline of the function of cells, organs and organisms over time. At the molecular and cellular level, the concept of biological age has been established and novel biomarkers of biological age have been identified, notably epigenetic DNA-methylation based clocks. With the emergence of single-cell DNA methylation profiling methods, the possibility to study biological age of individual cells has been proposed, and a first proof-of-concept study, based on limited single cell datasets mostly from early developmental origin, indicated the feasibility and relevance of this approach to better understand organismal changes and cellular ageing heterogeneity. Here, we generated a large single-cell DNA methylation and matched transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages (10-101 weeks of age), and developed a robust single-cell DNA methylation age prediction model (scEpiAge-blood and also scEpiAge-liver). We find that our new scEpiAge can accurately predict age in a broad range of publicly available datasets, including very sparse data and it also predicts age in single cells. Interestingly, the epigenetic age distribution is wider than technically expected in 19% of single cells, suggesting that epigenetic age heterogeneity is present in vivo and may relate to functional differences between cells. In addition, we observe differences in epigenetic ageing between the major blood cell types. Our work provides a foundation for better single-cell and sparse data epigenetic age predictors and highlights the significance of cellular heterogeneity during ageing.
Project description:Ageing is the accumulation of changes and overall decline of the function of cells, organs and organisms over time. At the molecular and cellular level, the concept of biological age has been established and novel biomarkers of biological age have been identified, notably epigenetic DNA-methylation based clocks. With the emergence of single-cell DNA methylation profiling methods, the possibility to study biological age of individual cells has been proposed, and a first proof-of-concept study, based on limited single cell datasets mostly from early developmental origin, indicated the feasibility and relevance of this approach to better understand organismal changes and cellular ageing heterogeneity. Here, we generated a large single-cell DNA methylation and matched transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages (10-101 weeks of age), and developed a robust single-cell DNA methylation age prediction model (scEpiAge-blood and also scEpiAge-liver). We find that our new scEpiAge can accurately predict age in a broad range of publicly available datasets, including very sparse data and it also predicts age in single cells. Interestingly, the epigenetic age distribution is wider than technically expected in 19% of single cells, suggesting that epigenetic age heterogeneity is present in vivo and may relate to functional differences between cells. In addition, we observe differences in epigenetic ageing between the major blood cell types. Our work provides a foundation for better single-cell and sparse data epigenetic age predictors and highlights the significance of cellular heterogeneity during ageing.
Project description:Ageing is the accumulation of changes and overall decline of the function of cells, organs and organisms over time. At the molecular and cellular level, the concept of biological age has been established and novel biomarkers of biological age have been identified, notably epigenetic DNA-methylation based clocks. With the emergence of single-cell DNA methylation profiling methods, the possibility to study biological age of individual cells has been proposed, and a first proof-of-concept study, based on limited single cell datasets mostly from early developmental origin, indicated the feasibility and relevance of this approach to better understand organismal changes and cellular ageing heterogeneity. Here, we generated a large single-cell DNA methylation and matched transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages (10-101 weeks of age), and developed a robust single-cell DNA methylation age prediction model (scEpiAge-blood and also scEpiAge-liver). We find that our new scEpiAge can accurately predict age in a broad range of publicly available datasets, including very sparse data and it also predicts age in single cells. Interestingly, the epigenetic age distribution is wider than technically expected in 19% of single cells, suggesting that epigenetic age heterogeneity is present in vivo and may relate to functional differences between cells. In addition, we observe differences in epigenetic ageing between the major blood cell types. Our work provides a foundation for better single-cell and sparse data epigenetic age predictors and highlights the significance of cellular heterogeneity during ageing.
Project description:Recently a biochemistry experiment named methyl-3C was developed to simultaneously capture the chromosomal conformations and DNA methylation levels on individual single cells. However, the number of data sets generated from this experiment is still small in the scientific community compared with the greater amount of single-cell Hi-C data generated from separate single cells. Therefore, a computational tool to predict single-cell methylation levels based on single-cell Hi-C data on the same individual cells is needed. We developed a graph transformer named scHiMe to accurately predict the base-pair-specific (bp-specific) methylation levels based on both single-cell Hi-C data and DNA nucleotide sequences. We benchmarked scHiMe for predicting the bp-specific methylation levels on all of the promoters of the human genome, all of the promoter regions together with the corresponding first exon and intron regions, and random regions on the whole genome. Our evaluation showed a high consistency between the predicted and methyl-3C-detected methylation levels. Moreover, the predicted DNA methylation levels resulted in accurate classifications of cells into different cell types, which indicated that our algorithm successfully captured the cell-to-cell variability in the single-cell Hi-C data. scHiMe is freely available at http://dna.cs.miami.edu/scHiMe/.
Project description:Genome wide DNA methylation profiling of normal whole blood samples. The data consist of 100 samples with Illumina HumanMethylation450 BeadChip data.
Project description:DNA methylation is an important regulator of gene transcription. WGBS is the gold-standard approach for base-pair resolution quantitative of DNA methylation. It requires high sequencing depth. Many CpG sites with insufficient coverage in the WGBS data, resulting in inaccurate DNA methylation levels of individual sites. Many state-of-arts computation methods were proposed to predict the missing value. However, many methods required either other omics datasets or other cross-sample data. And most of them only predicted the state of DNA methylation. In this study, we proposed the RcWGBS, which can impute the missing (or low coverage) values from the DNA methylation levels on the adjacent sides. Deep learning techniques were employed for the accurate prediction. The WGBS datasets of H1-hESC and GM12878 were down-sampled. The average difference between the DNA methylation level at 12× depth predicted by RcWGBS and that at >50× depth in the H1-hESC and GM2878 cells are less than 0.03 and 0.01, respectively. RcWGBS performed better than METHimpute even though the sequencing depth was as low as 12×. Our work would help to process methylation data of low sequencing depth. It is beneficial for researchers to save sequencing costs and improve data utilization through computational methods.