Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network

Qian Gao,Wei Zhu,Naijun Chen,Huawei Jin,Wenjun Zhang,Guojun Yang,Tingting Li

doi:10.1038/s41598-021-03912-6

Abstract

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.

Highlights

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients
COVID-19 may affect Dipeptidyl peptidase-4 (DPP4) in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19
DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes

Summary

Materials and methods

Taking ‘diabetes mellitus’ as the keyword, diabetes mellitus-related targets were searched in GeneCards database (https://www.genecards.org/). Screening of protein targets directly associated with DPP4. The diabetes mellitus related target (obtained by step 2.1) and DPP4 were imported into STRING database (https://string-db.org/) 12 in the form of symbol to obtain the protein–protein interaction network map. The targets directly related to DPP4 were screened for further research. DPP4 and 43 related proteins were re-imported into STRING to obtain the protein–protein interaction network for subsequent analysis. The enrichment analysis of GO function and KEGG pathway analysis was carried out through STRING to predict its action mechanism and construct the network diagram. In order to further evaluate the impact of DPP4 on the whole network and the possible pathway, the module 1 where DPP4 is located is used as the internal network, the cross module association of internal network is screened out. The data are filtered with 0.6 (determined by mean and median) as the standard, the qualified cross module associated proteins and associated scores were listed, and the proteins included in module 1 and the cross module associated protein scores of module 1 were summed as the scores

Results

Discussion

Conclusions