Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), Córdoba, Argentina.
J Crohns Colitis. 2022 Nov 23;16(11):1651-1662. doi: 10.1093/ecco-jcc/jjac059.
BACKGROUND AND AIMS: Modern views accept that inflammatory bowel diseases [IBD] emerge from complex interactions among the multiple components of a biological network known as the 'IBD interactome'. These diverse components belong to different functional levels including cells, molecules, genes and biological processes. This diversity can make it difficult to integrate available empirical information from human patients into a collective view of aetiopathogenesis, a necessary step to understand the interactome. Herein, we quantitatively analyse how the representativeness of components involved in human IBD and their relationships ha ve changed over time. METHODS: A bibliographic search in PubMed retrieved 25 971 abstracts of experimental studies on IBD in humans, published between 1990 and 2020. Abstracts were scanned automatically for 1218 IBD interactome components proposed in recent reviews. The resulting databases are freely available and were visualized as networks indicating the frequency at which different components are referenced together within each abstract. RESULTS: As expected, over time there was an increase in components added to the IBD network and heightened connectivity within and across functional levels. However, certain components were consistently studied together, forming preserved motifs in the networks. These overrepresented and highly linked components reflect main 'hypotheses' in IBD research in humans. Interestingly, 82% of the components cited in reviews were absent or showed low frequency, suggesting that many aspects of the proposed IBD interactome still have weak experimental support in humans. CONCLUSIONS: A reductionist and fragmented approach to the study of IBD has prevailed in previous decades, highlighting the importance of transitioning towards a more integrated interactome framework.
背景与目的:现代观点认为,炎症性肠病[IBD]是由被称为“IBD 相互作用组”的生物网络的多个组成部分之间的复杂相互作用产生的。这些不同的组成部分属于不同的功能层次,包括细胞、分子、基因和生物过程。这种多样性可能使得难以将来自人类患者的现有经验信息整合到发病机制的综合观点中,这是理解相互作用组的必要步骤。在此,我们定量分析了参与人类 IBD 的成分及其相互关系的代表性随时间的变化。
方法:在 PubMed 中进行文献检索,检索了 1990 年至 2020 年间发表的人类 IBD 实验研究的 25971 篇摘要。自动扫描摘要中最近综述中提出的 1218 个 IBD 相互作用组成分。由此产生的数据库是免费提供的,并以网络形式可视化,表明在每个摘要中不同成分一起被引用的频率。
结果:正如预期的那样,随着时间的推移,添加到 IBD 网络中的成分增加了,并且功能层次内和跨功能层次的连接性增强了。然而,某些成分一直被一起研究,在网络中形成了保存的基序。这些被过度代表且高度连接的成分反映了人类 IBD 研究中的主要“假说”。有趣的是,82%的综述中引用的成分缺失或出现频率较低,这表明提出的 IBD 相互作用组的许多方面在人类中仍然缺乏强有力的实验支持。
结论:在过去几十年中,对 IBD 的研究一直采用还原论和碎片化的方法,这凸显了向更综合的相互作用组框架转变的重要性。
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