Hemedan Ahmed Abdelmonem, Satagopam Venkata, Schneider Reinhard, Ostaszewski Marek
Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
iScience. 2024 Sep 14;27(10):110956. doi: 10.1016/j.isci.2024.110956. eCollection 2024 Oct 18.
Parkinson's disease (PD) involves complex molecular interactions and diverse comorbidities. To better understand its molecular mechanisms, we employed systems medicine approaches using the PD map, a detailed repository of PD-related interactions and applied Probabilistic Boolean Networks (PBNs) to capture the stochastic nature of molecular dynamics. By integrating cohort-level and real-world patient data, we modeled PD's subtype-specific pathway deregulations, providing a refined representation of its molecular landscape. Our study identifies key regulatory biomolecules and pathways that vary across PD subtypes, offering insights into the disease's progression and patient stratification. These findings have significant implications for the development of targeted therapeutic interventions.
帕金森病(PD)涉及复杂的分子相互作用和多种合并症。为了更好地理解其分子机制,我们采用了系统医学方法,利用帕金森病图谱这一详细的帕金森病相关相互作用知识库,并应用概率布尔网络(PBN)来捕捉分子动力学的随机性。通过整合队列水平和真实世界患者数据,我们对帕金森病亚型特异性通路失调进行了建模,提供了其分子景观的精确表征。我们的研究确定了在不同帕金森病亚型中存在差异的关键调节生物分子和通路,为该疾病的进展和患者分层提供了见解。这些发现对靶向治疗干预的开发具有重要意义。