Dataset Information

Expression correlation attenuates within and between key signaling pathways in chronic kidney disease.

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.

SUBMITTER: Yu H

PROVIDER: S-EPMC7504859 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Expression correlation attenuates within and between key signaling pathways in chronic kidney disease.

Yu Hui H Chen Danqian D Oyebamiji Olufunmilola O Zhao Ying-Yong YY Guo Yan Y

BMC medical genomics 20200921 Suppl 9

<h4>Background</h4>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 differe ...[more]

PMID: 32957963

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Project description:Chronic kidney disease (CKD) is a highly heterogeneous nephrosis that occurs when the structure and function of the kidney is damaged. Gene expression studies have been widely used to elucidate various biological processes; however, the gene expression profile of CKD is currently unclear. The present study aimed to identify diagnostic biomarkers and therapeutic targets using renal biopsy sample data from patients with CKD. Gene expression data from 30 patients with CKD and 21 living donors were analyzed by weighted gene co‑expression network analysis (WGCNA), in order to identify gene networks and profiles for CKD, as well as its specific characteristics, and to potentially uncover diagnostic biomarkers and therapeutic targets for patients with CKD. In addition, functional enrichment analysis was performed on co‑expressed genes to determine modules of interest. Four co‑expression modules were constructed from the WGCNA. The number of genes in the constructed modules ranged from 269 genes in the Turquoise module to 60 genes in the Yellow module. All four co‑expression modules were correlated with CKD clinical traits (P<0.05). For example, the Turquoise module, which mostly contained genes that were upregulated in CKD, was positively correlated with CKD clinical traits, whereas the Blue, Brown and Yellow modules were negatively correlated with clinical traits. Functional enrichment analysis revealed that the Turquoise module was mainly enriched in genes associated with the 'defense response', 'mitotic cell cycle' and 'collagen catabolic process' Gene Ontology (GO) terms, implying that genes involved in cell cycle arrest and fibrogenesis were upregulated in CKD. Conversely, the Yellow module was mainly enriched in genes associated with 'glomerulus development' and 'kidney development' GO terms, indicating that genes associated with renal development and damage repair were downregulated in CKD. The hub genes in the modules were acetyl‑CoA carboxylase α, cyclin‑dependent kinase 1, Wilm's tumour 1, NPHS2 stomatin family member, podocin, JunB proto‑oncogene, AP‑1 transcription factor subunit, activating transcription factor 3, forkhead box O1 and v‑abl Abelson murine leukemia viral oncogene homolog 1, which were confirmed to be significantly differentially expressed in CKD biopsies. Combining the eight hub genes enabled a high capacity for discrimination between patients with CKD and healthy subjects, with an area under the receiver operating characteristic curve of 1.00. In conclusion, this study provided a framework for co‑expression modules of renal biopsy samples from patients with CKD and living donors, and identified several potential diagnostic biomarkers and therapeutic targets for CKD.

Dataset Information

Expression correlation attenuates within and between key signaling pathways in chronic kidney disease.

Background

Methods

Results

Conclusions

Publications

Expression correlation attenuates within and between key signaling pathways in chronic kidney disease.

Similar Datasets

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