Barajas-Martínez Antonio, Ibarra-Coronado Elizabeth, Sierra-Vargas Martha Patricia, Cruz-Bautista Ivette, Almeda-Valdes Paloma, Aguilar-Salinas Carlos A, Fossion Ruben, Stephens Christopher R, Vargas-Domínguez Claudia, Atzatzi-Aguilar Octavio Gamaliel, Debray-García Yazmín, García-Torrentera Rogelio, Bobadilla Karen, Naranjo Meneses María Augusta, Mena Orozco Dulce Abril, Lam-Chung César Ernesto, Martínez Garcés Vania, Lecona Octavio A, Marín-García Arlex O, Frank Alejandro, Rivera Ana Leonor
Posgrado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Front Physiol. 2021 Jan 12;11:612598. doi: 10.3389/fphys.2020.612598. eCollection 2020.
Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a -value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the -value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.
目前,生理学研究聚焦于生物体功能背后的分子机制。还原论策略被用于将系统分解为其组成部分,并测量实验条件之间生理变量的变化。然而,这些孤立的生理变量如何转化为整个生物体生物学功能的出现和崩溃,往往是一个较难处理的问题。为了生成生理学作为一个系统的有用表示,必须考虑异构生理成分之间已知和未知的相互作用。在这项工作中,我们使用复杂推理网络方法从生物标志物构建生理网络。我们使用两个不相关的数据库分别生成81个和54个生理变量的斯皮尔曼相关矩阵,包括内分泌、力学、生化、人体测量、生理和细胞变量。从这些相关矩阵中,我们通过选择一个表示统计显著联系的p值阈值来生成生理网络。我们比较了两个样本的网络,以显示哪些特征对于健康生理学是稳健和有代表性的。我们发现,虽然网络拓扑对p值阈值敏感,但可以通过结合拓扑特征稳定性和网络连通性的标准来定义一个最佳值。无监督社区检测算法能够获得与当前医学知识相关性良好的功能簇。最后,我们描述了生理网络的拓扑结构,它介于随机和有序结构特征之间,可能反映系统的稳健性和适应性。生理网络的模块化允许探索即使在考虑不同生理变量时也一致的功能簇。总之,来自生物标志物的复杂推理网络提供了一种系统生物学方法的有效实现,这种方法在视觉上易于理解且稳健。我们假设生理网络能够将诸如内稳态等概念转化为生物系统的可量化属性,这对于健康和疾病的确定及量化是有用的。