The thoracic aortic aneurysms especially ascending aortic aneurysms are lethal and tend to be rupture and dissected. The prognosis of untreated aortic aneurysms is worse compared with surgical treatment, however surgical treatment is still a challenging operation with massive trauma and hard to perform on the appropriate time. Medical treatment is mainly to treat the risk factors but not the pathogenesis. With the exploration of the mechanisms of the diseases from onset to development till deterioration or even death leading, the medicine treatment of aortic aneurysms will become more well-targeted and effective.
The single cell RNA sequencing is widely used to reveal the function of an individual cell in the context of its microenvironment. After the gene differences study at the cell clusters level, we attempt to obtain the overall differential expression analysis through the algorithm on this basis. This is not only an overall exploration of the mechanism of this disease, but also an attempt to propose a new analytical method to incorporate both local and holistic results from the single-cell sequencing outcome.
All DEGs are obtained by starting from the processing of the original samples. After ensuring no statistical significance, we extracted gene expression array and finally to the results intersection of the edgeR and DESeq models. The following part is bioinformatics analysis process, including enrichment analysis such as GO analysis and KEGG pathways, the presentation of PPI network, and the target prediction associated with network analysis used to select the hub genes.
By comparing the gene expression of normal ascending aorta tissue and ascending aorta tissue of ATAA patients, we screened 1390 DEGs, including 526 up-regulated DEGs and 864 down-regulated DEGs. The selected hub genes are: CDC20, CCNB2, BUB1B, BIRC5, PTTG1, ESPL1, PPP1R12B, MYLK, MYL9, MYH14, MYH11. In the classification process using k-means clustering algorithm, MYLK and MYH11 gene showed the characteristics of being in the center and difficult to be classified, indicating that they have a certain pivotal effect. It is consistent with the observation of the characteristics of the small world network. The results obtained by this method is highly compatible with the consensus，and can explain the mechanisms of the aortic aneurysms progressing.
CDC20, CCNB2, BUB1B, BIRC5, PTTG1, ESPL1 genes as down-regulated hub genes, PPP1R12B, MYLK, MYL9, MYH14, MYH11 were up-regulated hub genes associated with ATAA. MYLK and MYH11 are in the strong group in the consensus of experts. Also, we provided a method to convert single-cell mRNA sequencing results to whole-exome sequencing results, thereby enabling further thinking about molecular pathways of disease at the global and local level in single cell sequencing result.