MaaD-TAD: an all-atom model of the duplicated PRAMEF/HNRNPCL chromatin domain built from sequence homology

MaaD-TAD builds the first all-atom model of a complete TAD at the PRAMEF/HNRNPCL locus on human chromosome 1, totaling 3,359 nucleosomes and ~55 million atoms.

• Why it matters: Hi-C and nucleosome maps often have missing “void regions” in duplicated genomic segments, limiting 3D TAD modeling and leaving uncertainty about how homologous copies are positioned in space.
• What they did: The pipeline replaces missing Hi-C with a sequence-homology map, folds it with CSynth, lengthens the path to a chromatin fibre, and refines using cohesin and CTCF site placement.
• The result: Micro-C data from two other duplicated regions support the homology-proximity hypothesis, with matching copies contacting 1.2–1.9 times more often than expected.

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