A Mechanism-Informed Deep Neural Network Enables Prioritization of Regulators That Drive Cell State Transitions

    February 2025 in “ Nature Communications
    Xi Xi, Jiaqi Li, Jinmeng Jia, Qiuchen Meng, Chen Li, Xiaowo Wang, Lei Wei, Xuegong Zhang
    TLDR A new neural network helps identify key regulators in cell changes, aiding in understanding diseases and finding new treatments.
    The study introduces regX, a deep neural network designed to prioritize regulators driving cell state transitions by incorporating gene-level regulation and gene-gene interaction mechanisms. Applied to single-cell multi-omics data on type 2 diabetes and hair follicle development, regX effectively identifies key transcription factors and candidate cis-regulatory elements. This approach not only aids in understanding cellular events but also highlights potential new therapeutic targets, drug repurposing opportunities, and causal single nucleotide polymorphisms. The research demonstrates the advantage of using interpretable neural networks to decode complex biological systems.
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