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通过整合系统生物学将儿童过敏性哮喘表型与内型联系起来:当前证据和研究需求。

Linking childhood allergic asthma phenotypes with endotype through integrated systems biology: current evidence and research needs.

作者信息

Choi Hyunok, Song Won-Min, Zhang Bin

出版信息

Rev Environ Health. 2017 Mar 1;32(1-2):55-63. doi: 10.1515/reveh-2016-0054.

Abstract

Asthma and other complex diseases results from a complex web of interactions involving inflammation, immunity, cell cycle, apoptosis, and metabolic perturbations across multiple organ systems. The extent to which various degrees of the age at onset, symptom severity, and the natural progression of the disease reflect multiple disease subtypes, influenced by unique process of development remains unknown. One of the most critical challenges to our understanding stems from incomplete understanding of the mechanisms. Within this review, we focus on the phenotypes of childhood allergic asthma as the basis to better understand the endotype for quantitative define subtypes of asthma. We highlight some of the known mechanistic pathways associated with the key hallmark events before the asthma onset. In particular, we examine how the recent advent of multiaxial -omics technologies and systems biology could help to clarify our current understanding of the pathway. We review how a large volume of molecular, genomic data generated by multiaxial technologies could be digested to identify cogent pathophysiologic molecular networks. We highlight some recent successes in application of these technologies within the context of other disease conditions for therapeutic interventions. We conclude by summarizing the research needs for the predictive value of preclinical biomarkers.

摘要

哮喘和其他复杂疾病是由多个器官系统中涉及炎症、免疫、细胞周期、细胞凋亡和代谢紊乱的复杂相互作用网络导致的。不同发病年龄、症状严重程度以及疾病自然进展的各个程度在多大程度上反映了受独特发育过程影响的多种疾病亚型,目前尚不清楚。我们理解该疾病的最关键挑战之一源于对其机制的不完全理解。在本综述中,我们聚焦于儿童过敏性哮喘的表型,以此为基础更好地理解哮喘亚型定量定义的内型。我们强调了一些与哮喘发作前关键标志性事件相关的已知机制途径。特别是,我们探讨了多轴组学技术和系统生物学的最新进展如何有助于阐明我们目前对该途径的理解。我们回顾了多轴技术产生的大量分子、基因组数据如何能够被剖析以识别有说服力的病理生理分子网络。我们强调了这些技术在其他疾病状况下用于治疗干预的一些近期成功应用。我们通过总结临床前生物标志物预测价值的研究需求来得出结论。

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