Combined analysis of whole-exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity

Abstract

This study sought to find more exon mutation sites and lncRNA candidates associated with type 2 diabetes mellitus (T2DM) patients with obesity (O-T2DM). We used O-T2DM patients and healthy individuals to detect mutations in their peripheral blood by whole-exon sequencing. And changes in lncRNA expression caused by mutation sites were studied at the RNA level. Then, we performed GO analysis and KEGG pathway analysis. We found a total of 277 377 mutation sites between O-T2DM and healthy individuals. Then, we performed a DNA-RNA joint analysis. Based on the screening of harmful sites, 30 mutant genes shared in O-T2DM patients were screened. At the RNA level, mutations of 106 differentially expressed genes were displayed. Finally, a consensus mutation site and differential expression consensus gene screening were performed. In the current study, the results revealed significant differences in exon sites in peripheral blood between O-T2DM and healthy individuals, which may play an important role in the pathogenesis of O-T2DM by affecting the expression of the corresponding lncRNA. This study provides clues to the molecular mechanisms of metabolic disorders in O-T2DM patients at the DNA and RNA levels, as well as biomarkers of the risk of these disorders.

Keywords: diabetes; long non-coding RNA; mutation sites; obesity.

Figure 1

The histogram of GO enriched. A, Biological process, B, cellular component and C, molecular function

Figure 2

Scatter plot of the KEGG pathway enrichment. Abscissa indicates the proportion of genes enriched in the pathway to the total enriched gene, and the ordinate indicates the name of the enriched KEGG pathway. The dot size indicates the number of genes enriched in the pathway, and the colour indicates the P‐value

Figure 3

Gene‐phenotype‐disease association network. The size of the shape covered by the gene name represents the strength of the association with the disease, and the larger the shape coverage area, the stronger the correlation with the disease. A Green dot indicates a gene that is considered to be associated with a related disease in an existing report or database; an orange dot indicates a gene that is considered to be related to a green gene based on various associations

Figure 4

Top 20 candidate genes ranked in association with O‐T2DM. The relevance score is 1 for the maximum

Figure 5

Co‐expression network

Figure 6

Changes in the expression levels of mutant genes and mutant genes in O‐T2DM patients. A, Mutant genes shared by O‐T2DM patients. The heat map of the consensus mutation gene obtained by screening at the genome level, different colours indicate different mutation types. B, Heat map of mutated gene expression levels in O‐T2DM patients. This figure shows the change in the corresponding expression level of the high frequency mutant gene, expressed as FPKM, and the colour from red to blue indicates the FPKM from large to small

Figure 7

Heat map of mutant genes and differentially expressed genes in O‐T2DM patients. A, Mutant genes. B, Significant differentially expressed genes