Mbuguiro Wangui, Gonzalez Adriana Noemi, Mac Gabhann Feilim
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Institute for Computational Medicine, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States.
Front Reprod Health. 2021 Dec 20;3:699133. doi: 10.3389/frph.2021.699133. eCollection 2021.
Endometriosis is a common but poorly understood disease. Symptoms can begin early in adolescence, with menarche, and can be debilitating. Despite this, people often suffer several years before being correctly diagnosed and adequately treated. Endometriosis involves the inappropriate growth of endometrial-like tissue (including epithelial cells, stromal fibroblasts, vascular cells, and immune cells) outside of the uterus. Computational models can aid in understanding the mechanisms by which immune, hormone, and vascular disruptions manifest in endometriosis and complicate treatment. In this review, we illustrate how three computational modeling approaches (regression, pharmacokinetics/pharmacodynamics, and quantitative systems pharmacology) have been used to improve the diagnosis and treatment of endometriosis. As we explore these approaches and their differing detail of biological mechanisms, we consider how each approach can answer different questions about endometriosis. We summarize the mathematics involved, and we use published examples of each approach to compare how researchers: (1) shape the scope of each model, (2) incorporate experimental and clinical data, and (3) generate clinically useful predictions and insight. Lastly, we discuss the benefits and limitations of each modeling approach and how we can combine these approaches to further understand, diagnose, and treat endometriosis.
子宫内膜异位症是一种常见但了解甚少的疾病。症状可在青春期早期月经初潮时就开始出现,且可能使人虚弱。尽管如此,人们往往要忍受数年才得到正确诊断和充分治疗。子宫内膜异位症涉及子宫内膜样组织(包括上皮细胞、基质成纤维细胞、血管细胞和免疫细胞)在子宫外的异常生长。计算模型有助于理解免疫、激素和血管紊乱在子宫内膜异位症中表现出来并使治疗复杂化的机制。在本综述中,我们阐述了三种计算建模方法(回归分析、药代动力学/药效学和定量系统药理学)如何被用于改善子宫内膜异位症的诊断和治疗。在我们探索这些方法及其不同的生物学机制细节时,我们思考了每种方法如何回答关于子宫内膜异位症的不同问题。我们总结了其中涉及的数学知识,并使用每种方法已发表的实例来比较研究人员如何:(1)界定每个模型的范围,(2)纳入实验和临床数据,以及(3)生成具有临床实用性的预测和见解。最后,我们讨论了每种建模方法的优缺点,以及我们如何结合这些方法来进一步理解、诊断和治疗子宫内膜异位症。