A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics.

Systems and Synthetic Biology Pub Date : 2014-03-01 Epub Date: 2013-09-18 DOI:10.1007/s11693-013-9125-3
Pramod Rajaram Somvanshi, K V Venkatesh
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引用次数: 52

Abstract

Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable physiological state termed as disease. Here, we treat a disease diagnosis problem analogous to a fault diagnosis problem in engineering systems. Accordingly we review the application of engineering methodologies to address human diseases from systems biological perspective. The review highlights potential networks and modeling approaches used for analyzing human diseases. The application of such analysis is illustrated in the case of cancer and diabetes. We put forth a concept of cell-to-human framework comprising of five modules (data mining, networking, modeling, experimental and validation) for addressing human physiology and diseases based on a paradigm of system level analysis. The review overtly emphasizes on the importance of multi-scale biological networks and subsequent modeling and analysis for drug target identification and designing efficient therapies.

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健康和疾病系统生物学的概念综述:从生物网络到现代治疗学。
人体生理学是一个从细胞内分子相互作用到全身表型反应的各种生物过程的集合。系统生物学持续破译这些多尺度的生物网络,并在基因型和表型之间架起桥梁。这些网络的结构和动态特性负责控制和决定细胞的表型状态。几个细胞和各种组织协同产生器官水平的反应,从而进一步调节最终的生理状态。整个网络嵌入了一个分层调节结构,当异常干扰时,可导致不良的生理状态,称为疾病。在这里,我们对待疾病诊断问题类似于工程系统中的故障诊断问题。因此,我们从系统生物学的角度回顾了工程方法在解决人类疾病方面的应用。这篇综述强调了用于分析人类疾病的潜在网络和建模方法。这种分析的应用在癌症和糖尿病的案例中得到了说明。我们提出了一个基于系统级分析范式的人体生理和疾病研究的细胞-人框架概念,该框架包括五个模块(数据挖掘、网络、建模、实验和验证)。该综述明确强调了多尺度生物网络及其后续建模和分析对药物靶点识别和设计有效疗法的重要性。
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