Project description:In this study, we have optimized and directly compared epigenetic age predictors based on pyrosequencing, ddPCR and BBA-seq of specific age-associated regions. Bisulfite barcoded amplicon sequencing (BBA-seq) was performed on 9 genomic region of 77 human blood DNA and 11 genomic regions of 95 buccal swab DNA to measure age-associated regions for epigenetic age prediction. Furthermore, our data indicate that the correlation of age-associated DNAm with chronological age peaks close to CTCF binding sites. Age-associated DNAm is not coherently modified on individual DNA strands and this enabled alternative single-read age-predictors that reflect heterogeneity in epigenetic aging within a specimen.
Project description:Age-associated DNA methylation reflects aspect of biological aging - therefore epigenetic clocks for mice can help to elucidate the impact of treatments or genetic background on the aging process in this model organism. Initially, age-predictors for mice were trained for genome-wide DNA methylation profiles and we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three CG dinucleotides (CpGs). Here, we have re-evaluated pyrosequencing approaches in comparison to droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CpGs the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified at murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the epigenetic age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe further optimized and alternative targeted methods to determine epigenetic clocks in mice.
Project description:Since their introduction, epigenetic clocks have been extensively used in aging and human disease research. In this study, we reveal an intriguing pattern: epigenetic age predictions display a 24-hour periodicity. These paradoxical age oscillations can be attributed to variations in blood cell type composition and epigenomes, both of which demonstrate circadian rhythmicity. This discovery emphasizes the significance of factoring-in the time of day to obtain accurate estimates of epigenetic age.
Project description:Since their introduction, epigenetic clocks have been extensively used in aging and human disease research. In this study, we reveal an intriguing pattern: epigenetic age predictions display a 24-hour periodicity. These paradoxical age oscillations can be attributed to variations in blood cell type composition and epigenomes, both of which demonstrate circadian rhythmicity. This discovery emphasizes the significance of factoring-in the time of day to obtain accurate estimates of epigenetic age.
Project description:Since their introduction, epigenetic clocks have been extensively used in aging and human disease research. In this study, we reveal an intriguing pattern: epigenetic age predictions display a 24-hour periodicity. These paradoxical age oscillations can be attributed to variations in blood cell type composition and epigenomes, both of which demonstrate circadian rhythmicity. This discovery emphasizes the significance of factoring-in the time of day to obtain accurate estimates of epigenetic age.
Project description:We report a high-throughput and low-cost targeted bisulfite sequencing method called TIME-Seq for discovery and assay of DNA methylation clocks. Data is related to the initial publication of TIME-Seq clocks and shallow sequencing-based predictions using scAge. Demultiplexing information as well as more detailed metadata for each sample in the pools will be posted at: https://github.com/patricktgriffin/TIME-Seq
Project description:In this study, we report the first examination of Medulloblastoma (MB) methylation patterns in Arab world, using an extensive primary tumor cohort in tertiray care center. We assessed DNA methylation patterns to sub-classify clinical MB cases and their amenability to clinical applications from archival biopsy material (FPPE). We herein establish methylation events as clinically useful biomarkers and demonstrate how their incorporation into current risk-stratification schemes could significantly improve the accuracy of survival predictions in clinical setting. This holds potential for future precision therapeutic approaches aimed at improving the outcomes of afflicted MB patients.