Hossain Intekhab, Fanfani Viola, Fischer Jonas, Quackenbush John, Burkholz Rebekka
bioRxiv. 2024 Jan 3:2023.02.24.529835. doi: 10.1101/2023.02.24.529835.
Modeling dynamics of gene regulatory networks using ordinary differential equations (ODEs) allow a deeper understanding of disease progression and response to therapy, thus aiding in intervention optimization. Although there exist methods to infer regulatory ODEs, these are generally limited to small networks, rely on dimensional reduction, or impose non-biological parametric restrictions - all impeding scalability and explainability. PHOENIX is a neural ODE framework incorporating prior domain knowledge as soft constraints to infer sparse, biologically interpretable dynamics. Extensive experiments - on simulated and real data - demonstrate PHOENIX's unique ability to learn key regulatory dynamics while scaling to the whole genome.
使用常微分方程(ODE)对基因调控网络的动力学进行建模,有助于更深入地理解疾病进展和对治疗的反应,从而有助于优化干预措施。尽管存在推断调控ODE的方法,但这些方法通常仅限于小型网络,依赖于降维,或施加非生物学的参数限制——所有这些都阻碍了可扩展性和可解释性。PHOENIX是一个神经ODE框架,它将先验领域知识作为软约束,以推断稀疏的、具有生物学可解释性的动力学。在模拟数据和真实数据上进行的大量实验表明,PHOENIX具有独特的能力,能够学习关键的调控动力学,同时扩展到全基因组范围。