Unified high-resolution immune cell fraction estimation in blood tissue from birth to old age

• Published in: Genome medicine Vol. 17; no. 1; pp. 63 - 26
• Main Authors: Guo, Xiaolong, Sulaiman, Mahnoor, Neumann, Alexander, Zheng, Shijie C., Cecil, Charlotte A.M., Teschendorff, Andrew E., Heijmans, Bastiaan T.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.05.2025; BioMed Central Ltd; BMC
• Subjects: Adolescent; Adult; Adults; Advances in healthy aging and age-related diseases; Aged; Algorithms; B cells; Bioinformatics; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Births; Blood; Cancer Research; Cell-type deconvolution; Cells; Child; Child, Preschool; Children; Children & youth; Cord blood; Datasets; Diabetes mellitus; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; DNA Methylation; Epigenetics; EWAS; Female; Granulocytes; Human Genetics; Humans; Immune system; Infant; Infant, Newborn; Infants; Longitudinal Studies; Lymphocytes; Male; Medicine/Public Health; Metabolomics; Methodology; Neonates; Protocol; Sex chromosomes; Systems Biology; Teenagers; China; DNA methylation; Cell-type deconvolution; Cord blood; EWAS; Immune system
• ISSN: 1756-994X; 1756-994X
• DOI: 10.1186/s13073-025-01489-7

Variations in immune-cell fractions can confound or hamper interpretation of DNAm-based biomarkers in blood. Although cell-type deconvolution can address this challenge for cord and adult blood, currently there is no method applicable to blood from other age groups, including infants and children. Here we construct and extensively validate a DNAm reference panel, called UniLIFE, for 19 immune cell-types, applicable to blood tissue of any age. We use UniLIFE to delineate the dynamics of immune-cell fractions from birth to old age, and to infer disease associated immune cell fraction variations in newborns, infants, children and adults. In a prospective longitudinal study of type-1 diabetes in infants and children, UniLIFE identifies differentially methylated positions that precede type-1 diabetes diagnosis and that map to diabetes related signaling pathways. In summary, UniLIFE will improve the identification and interpretation of blood-based DNAm biomarkers for any age group, but specially for longitudinal studies that include infants and children. The UniLIFE panel and algorithms to estimate cell-type fractions are available from our EpiDISH Bioconductor R-package: https://bioconductor.org/packages/release/bioc/html/EpiDISH.html