Expression correlation attenuates within and between key signaling pathways in chronic kidney disease
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RESEARCH
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Expression correlation attenuates within and between key signaling pathways in chronic kidney disease Hui Yu1, Danqian Chen2, Olufunmilola Oyebamiji1, Ying-Yong Zhao2* and Yan Guo1* From The International Conference on Intelligent Biology and Medicine (ICIBM) 2019 Columbus, OH, USA. 9-11 June 2019
Abstract Background: 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. Methods: 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. Results: 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. Conclusions: 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. Keywords: Chronic kidney disease, Differential co-expression, Correlation attenuation, Pathway crosstalk
Background Chronic kidney disease (CKD) entails gradual loss of kidney function leading to end-stage renal disease, precipitating the need for renal replacement therapies. The * Correspondence: [email protected]; [email protected] 2 Key Laboratory of Resource Biology and Biotechnology in Western China, School of Life Sciences, Northwest University, Xi’an 710069, Shaanxi, China 1 Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA
early stages of CKD, stages 1–2, have little signs or symptoms and the disease is often not detected until the later stages [1]. The risk of cardiovascular morbidity and mortality increases with the progression of CKD to stages 3–5. Omics-based approaches have emerged and explained the molecular differential expression dur
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