biostudies-literatureUnknown34(6)Yan BMultiomics require concerted recording of independent information, ideally from a single experiment. In this study, we introduce RIMS-seq2, a high-throughput technique to simultaneously sequence genomes and overlay methylation information while requiring only a small modification of the experimental protocol for high-throughput DNA sequencing to include a controlled deamination step. Importantly, the rate of deamination of 5-methylcytosine is negligible and thus does not interfere with standard DNA sequencing and data processing. Thus, RIMS-seq2 libraries from whole- or targeted-genome sequencing show the same germline variation calling accuracy and sensitivity compared with standard DNA-seq. Additionally, regional methylation levels provide an accurate map of the human methylome.Genome research904-913https://www.ebi.ac.uk/biostudies/studies/S-EPMC11293541biostudies-literatureSimultaneous assessment of human genome and methylome data in a single experiment using limited deamination of methylated cytosine.PMC11293541Ettwiller LWang DYan BfalseSimultaneous assessment of human genome and methylome data in a single experiment using limited deamination of methylated cytosine.Multiomics require concerted recording of independent information, ideally from a single experiment. In this study, we introduce RIMS-seq2, a high-throughput technique to simultaneously sequence genomes and overlay methylation information while requiring only a small modification of the experimental protocol for high-throughput DNA sequencing to include a controlled deamination step. Importantly, the rate of deamination of 5-methylcytosine is negligible and thus does not interfere with standard DNA sequencing and data processing. Thus, RIMS-seq2 libraries from whole- or targeted-genome sequencing show the same germline variation calling accuracy and sensitivity compared with standard DNA-seq. Additionally, regional methylation levels provide an accurate map of the human methylome.2024-01-01T00:00:00Z2024 Jul2026-05-02T12:31:55.527Z2024-12-03T19:34:20.36ZS-EPMC112935413885808710.1101/gr.278294.123