Compared to the conventional differential expression approach, differential coexpression analysis represents a different yet complementary perspective into diseased transcriptomes. In particular, global loss of transcriptome correlation was previously observed in aging mice, and a most recent study found genetic and environmental perturbations on human subjects tended to cause universal attenuation of transcriptome coherence. While methodological progresses surrounding differential coexpression have helped with research on several human diseases, there has not been an investigation of coexpression disruptions in chronic kidney disease (CKD) yet. RNA-seq was performed on total RNAs of kidney tissue samples from 140 CKD patients. A combination of differential coexpression methods were employed to analyze the transcriptome transition in CKD from the early, mild phase to the late, severe kidney damage phase. We discovered a global expression correlation attenuation in CKD progression, with pathway Regulation of nuclear SMAD2/3 signaling demonstrating the most remarkable intra-pathway correlation rewiring. Moreover, the pathway Signaling events mediated by focal adhesion kinase displayed significantly weakened crosstalk with seven pathways, including Regulation of nuclear SMAD2/3 signaling. Well-known relevant genes, such as ACTN4, were characterized with widespread correlation disassociation with partners from a wide array of signaling pathways. Altogether, our analysis reported a global expression correlation attenuation within and between key signaling pathways in chronic kidney disease, and presented a list of vanishing hub genes and disrupted correlations within and between key signaling pathways, illuminating on the pathophysiological mechanisms of CKD progression.

中文翻译：

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慢性肾脏病关键信号通路内部和之间的表达相关性减弱。


与传统的差异表达方法相比，差异共表达分析代表了对患病转录组的不同但互补的视角。特别是，之前在衰老小鼠中观察到转录组相关性的整体丧失，而最近的一项研究发现，人类受试者的遗传和环境扰动往往会导致转录组一致性的普遍减弱。虽然围绕差异共表达的方法学进展有助于对几种人类疾病的研究，但尚未对慢性肾病 (CKD) 中的共表达破坏进行研究。对 140 名 CKD 患者肾组织样本的总 RNA 进行 RNA 测序。采用差异共表达方法的组合来分析 CKD 从早期轻度肾损伤阶段到晚期严重肾损伤阶段的转录组转变。我们发现 CKD 进展中存在全局表达相关性减弱，核 SMAD2/3 信号传导的通路调节显示出最显着的通路内相关性重连。此外，粘着斑激酶介导的信号通路事件与七个通路的串扰显着减弱，包括核 SMAD2/3 信号通路的调节。众所周知的相关基因，例如 ACTN4，其特征是与多种信号通路中的伙伴存在广泛的相关性分离。总而言之，我们的分析报告了慢性肾脏病关键信号通路内部和之间的整体表达相关性减弱，并提出了一系列消失的中心基因和关键信号通路内部和之间相关性被破坏的列表，阐明了 CKD 进展的病理生理机制。