The Human Development Multiomic Atlas (HDMA) is a sophisticated single-cell resource that maps chromatin accessibility and gene expression across 12 human fetal organs. Researchers utilized deep learning models to decode the complex regulatory syntax of DNA, identifying over one million regulatory elements that govern cell identity. This investigation revealed distinct "hard" and "soft" rules for how transcription factors cooperate based on their spacing and orientation. The study also discovered negative motifs that actively reduce genetic accessibility, providing a new perspective on how the genome is silenced. Finally, the atlas helps prioritize disease-associated genetic variants by predicting how specific mutations disrupt regulatory logic during development. This foundational work offers a comprehensive framework for understanding the cis-regulatory logic that drives human growth.

References:

• Liu B B, Jessa S, Kim S H, et al. Multiomics and deep learning dissect regulatory syntax in human development[J]. Nature, 2026: 1-14.