️ Episode 213: BRAIN-MAGNET: a functional atlas for non-coding variants

In this episode of PaperCast Base by Base, we explore BRAIN-MAGNET couples a ChIP-STARR-seq atlas of 148,198 neural regulatory elements with a validated convolutional neural network to predict enhancer activity and prioritize disease-relevant non-coding variants

Study Highlights:
The authors generated an activity-ranked functional genomics atlas of 148,198 non-coding regulatory elements in human neural stem cells. Comparative ChIP-STARR-seq revealed many elements are epigenetically primed in embryonic stem cells for later neural activity. BRAIN-MAGNET, a convolutional neural network trained on the atlas, predicts enhancer activity from DNA sequence and computes nucleotide-level contribution scores to identify functional motifs. The model outperformed other prioritization scores at tested loci and enabled prioritization and functional validation of both common GWAS SNPs and rare variants, including a putative RAB7A enhanceropathy.

Conclusion:
The NCRE atlas and BRAIN-MAGNET provide a functionally validated resource to interpret non-coding genetic variation relevant to neurodevelopment and neurological disease

Music:
Enjoy the music based on this article at the end of the episode.

Reference:
Deng R, Perenthaler E, Nikoncuk A, Yousefi S, Lanko K, Schot R, Maresca M, Medico-Salsench E, Sanderson LE, Parker MJ, van Ijcken WFJ, Park J, Sturm M, Haack TB, Roshchupkin GV, Mulugeta E, Barakat TS. BRAIN-MAGNET: A functional genomics atlas for interpretation of non-coding variants. Cell. 2026 Jan 22;189:1–20. https://doi.org/10.1016/j.cell.2025.10.029

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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