Development of Tissue-Specific Age Predictors Using DNA Methylation Data

DNA methylation patterns have been shown to change throughout the normal aging process. Several studies have found epigenetic aging markers using age predictors, but these studies only focused on blood-specific or tissue-common methylation patterns. Here, we constructed nine tissue-specific age prediction models using methylation array data from normal samples. The constructed models predict the chronological age with good performance (mean absolute error of 5.11 years on average) and show better performance in the independent test than previous multi-tissue age predictors. We also compared tissue-common and tissue-specific aging markers and found that they had different characteristics. Firstly, the tissue-common group tended to contain more positive aging markers with methylation values that increased during the aging process, whereas the tissue-specific group tended to contain more negative aging markers. Secondly, many of the tissue-common markers were located in Cytosine-phosphate-Guanine (CpG) island regions, whereas the tissue-specific markers were located in CpG shore regions. Lastly, the tissue-common CpG markers tended to be located in more evolutionarily conserved regions. In conclusion, our prediction models identified CpG markers that capture both tissue-common and tissue-specific characteristics during the aging process

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth