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.
Footnotes[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278294.123.
Freely available online through the Genome Research Open Access option.
Received July 19, 2023. Accepted June 4, 2024.
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