Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy.

Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy.
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DOI:
10.1371/journal.pone.0194225
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Priami C
Priami C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Parolo S;Marchetti L;Lauria M;Misselbeck K;Scott-Boyer MP;Caberlotto L;Priami C

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尽管杜氏肌营养不良症的遗传基础已为人所知近三十年,但该疾病的细胞和分子机制尚未完全了解,有效的治疗方法仍有待开发。在这项研究中,我们分析了通过 SomaLogic 技术从一组患者和匹配的健康受试者的血清中获得的蛋白质组学数据。我们开发了一个基于生物标志物识别和基于网络的途径分析的工作流程,使我们能够描述不同的解除管制途径。除了肌肉相关功能之外,我们还发现其他生物过程,例如细胞凋亡、免疫系统信号传导和神经营养蛋白信号传导,在患者中与对照组相比受到显着调节。此外,我们基于网络的分析确定了 FoxO 转录因子作为不同途径的假定调节剂的参与。总的来说,这项研究提供了杜氏肌营养不良症相关分子过程的全局视图,这些分子过程可从血清蛋白质组中解读。
Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways. In addition to muscle-related functions, we identified other biological processes such as apoptosis, signaling in the immune system and neurotrophin signaling as significantly modulated in patients compared with controls. Moreover, our network-based analysis identified the involvement of FoxO transcription factors as putative regulators of different pathways. On the whole, this study provided a global view of the molecular processes involved in Duchenne muscular dystrophy that are decipherable from serum proteome.
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