New targeted approaches for epigenetic age predictions
Background Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurem...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 June 2020
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| In: |
BMC biology
Year: 2020, Volume: 18 |
| ISSN: | 1741-7007 |
| DOI: | 10.1186/s12915-020-00807-2 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s12915-020-00807-2
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| Author Notes: | Yang Han, Julia Franzen, Thomas Stiehl, Michael Gobs, Chao-Chung Kuo, Miloš Nikolić, Jan Hapala, Barbara Elisabeth Koop, Klaus Strathmann, Stefanie Ritz-Timme and Wolfgang Wagner |
| Summary: | Background Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis. Results In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Conclusion Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands. |
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| Item Description: | Gesehen am 13.08.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1741-7007 |
| DOI: | 10.1186/s12915-020-00807-2 |