# DNA methylation

Cytosine methylation at plant CG sites is gained and lost spontaneously, far faster than DNA point mutation. Until now a single site's steady state could only be estimated from the epigenome itself, leaving open whether it is written in DNA or carried by chromatin. REED, built on the NTv3 backbone, predicts every cytosine's methylation from 10 kb of sequence, and that prediction is the site's set point; in Arabidopsis pedigrees, the rice germline and a 330-year-old poplar, the direction and the rate-implied equilibrium of measured epimutations followed it.

Cytosine methylation at plant CG sites is gained and lost spontaneously, far faster than DNA point mutation. Until now a single site's steady state could only be estimated from the epigenome itself, leaving open whether it is written in DNA or carried by chromatin. REED, built on the NTv3 backbone, predicts every cytosine's methylation from 10 kb of sequence, and that prediction is the site's set point; in Arabidopsis pedigrees, the rice germline and a 330-year-old poplar, the direction and the rate-implied equilibrium of measured epimutations followed it.

Raw nanopore current is continuous and has no native token vocabulary, and prior analyses built a separate model per task. Brieno first compresses the signal into discrete tokens with residual vector quantization, then pretrains a Transformer by masked-token prediction on 118 million reads, so frozen or fine-tuned features serve species identification, barcode demultiplexing, basecalling and methylation detection. On held-out runs, fine-tuned Brieno reached a read-level CpG 5mC AUROC of 0.978, above the 0.975 of Dorado's dedicated 5mCG model.

Raw nanopore current is continuous and has no native token vocabulary, and prior analyses built a separate model per task. Brieno first compresses the signal into discrete tokens with residual vector quantization, then pretrains a Transformer by masked-token prediction on 118 million reads, so frozen or fine-tuned features serve species identification, barcode demultiplexing, basecalling and methylation detection. On held-out runs, fine-tuned Brieno reached a read-level CpG 5mC AUROC of 0.978, above the 0.975 of Dorado's dedicated 5mCG model.

DNA methylation data lacked a general way to quantify differentiation state; EpiDiff trains a random forest on 1,298 differentiation-associated CpGs to output a continuous index from 0 to 1. It reached 0.97 classification accuracy in independent datasets and rose with age in many sorted cell types, underpinned by a developmental epigenetic drift toward the mesoderm lineage.

DNA methylation data lacked a general way to quantify differentiation state; EpiDiff trains a random forest on 1,298 differentiation-associated CpGs to output a continuous index from 0 to 1. It reached 0.97 classification accuracy in independent datasets and rose with age in many sorted cell types, underpinned by a developmental epigenetic drift toward the mesoderm lineage.