Jülich Supercomputing Centre

Using the DNA language model Nucleotide Transformer v3 on the JUPITER supercomputer, the team substituted each of roughly 3.12 billion positions of the telomere-to-telomere human reference genome with each of the three alternative bases and recorded how model predictions changed elsewhere, yielding a genome-wide directed map of nucleotide dependencies. These dependencies preferentially link evolutionarily conserved positions and repeatedly assemble into seven geometric structures called Relons, some outside current annotation. Combined with CADD, dependency features raised intronic-variant pathogenicity AUPRC from 0.299 to 0.356.

Using the DNA language model Nucleotide Transformer v3 on the JUPITER supercomputer, the team substituted each of roughly 3.12 billion positions of the telomere-to-telomere human reference genome with each of the three alternative bases and recorded how model predictions changed elsewhere, yielding a genome-wide directed map of nucleotide dependencies. These dependencies preferentially link evolutionarily conserved positions and repeatedly assemble into seven geometric structures called Relons, some outside current annotation. Combined with CADD, dependency features raised intronic-variant pathogenicity AUPRC from 0.299 to 0.356.