Paediatric DNA methylation profile scores: a systematic review and open-source atlas

Methylation profile scores (MPSs) have emerged as a useful tool to index exposures, biological states, or disease-related patterns, by aggregating information across many DNA methylation (DNAm) sites into a single score per individual. Although most MPSs to date have been trained and validated in adults, their use in early life (<18 years) is rapidly gaining momentum, as more cohorts profile DNAm during development, offering a window on exposures and vulnerability before disease onset. Here we systematically review early-life MPS studies (n = 119), covering 828 MPSs that span a wide range of exposures and traits. Overall, studies show substantial heterogeneity in design and reporting. Also, studies frequently apply MPSs trained in data from mismatched age groups, tissues, array or platforms, and ancestries, which may influence MPS performance. To address these limitations, we introduce DEMETRA (indepthlab-demetra.share.connect.posit.cloud), a searchable atlas of early-life MPSs to help users identify and select scores best suited to their study.