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Decemedip: hierarchical Bayesian modeling for cell type deconvolution of immunoprecipitation-based DNA methylome

ABSTRACT: MeDIP-seq is an enrichment-based DNA methylation profiling technique that measures abundance of methylated DNA. While this technique offers efficiency advantages over direct methylation profiling, it does not provide absolute quantification of DNAm necessary for cell type deconvolution. We introduce decemedip, a Bayesian hierarchical model for cell type deconvolution of methylated sequencing data that leverages reference atlases derived from direct methylation profiling. We demonstrate its accuracy and robustness through simulation studies and validation on cross-platform measurements, and highlight its utility in identifying tissue-specific and cancer-associated methylation signatures using MeDIP-seq profiling of patient-derived xenografts and cell-free DNA. decemedip is available at \url{https://github.com/nshen7/decemedip}.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290990 | GEO | 2025/03/31

REPOSITORIES: GEO

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Project description:Genome-wide DNA methylation profile of human spermatozoa using the meDIP technique and massively parallel sequencing. DNA methylation is an indispensible epigenetic modification required for regulating the expression of mammalian genomes. Immunoprecipitation-based methods for DNA methylome analysis are rapidly shifting the bottleneck in this field from data generation to data analysis, necessitating the development of better analytical tools. In particular, an inability to estimate absolute methylation levels remains a major analytical difficulty associated with immunoprecipitation-based DNA methylation profiling. To address this issue, we developed a cross-platform algorithm-Bayesian tool for methylation analysis (Batman)-for analyzing methylated DNA immunoprecipitation (MeDIP) profiles generated using oligonucleotide arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). We developed the latter approach to provide a high-resolution whole-genome DNA methylation profile (DNA methylome) of a mammalian genome. Strong correlation of our data, obtained using mature human spermatozoa, with those obtained using bisulfite sequencing suggest that combining MeDIP-seq or MeDIP-chip with Batman provides a robust, quantitative and cost-effective functional genomic strategy for elucidating the function of DNA methylation. ArrayExpress Release Date: 2008-06-10 Publication Title: A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis Publication Author List: Thomas A Down; Vardhman K Rakyan; Daniel J Turner; Paul Flicek; Heng Li; Eugene Kulesha; Stefan GrÃ¤f; Nathan Johnson; Javier Herrero; Eleni M Tomazou; Natalie P Thorne; Liselotte BÃ¤ckdahl; Marlis Herberth; Kevin L Howe; David K Jackson; Marcos M Miretti; John C Marioni; Ewan Birney; Tim J P Hubbard; Richard Durbin; Simon TavarÃ©; Stephan Beck Person Roles: submitter; investigator Person Last Name: Flicek Person First Name: Paul Person Mid Initial Person Email: flicek@ebi.ac.uk Person Address: Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK Person Affiliation: European Bioinformatics Institute

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Decemedip: hierarchical Bayesian modeling for cell type deconvolution of immunoprecipitation-based DNA methylome

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