Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is a metabolic disease leading threat to human health around the world. Here we aimed to explore new biomarkers and potential therapeutic targets in T1DM through adopting integrated bioinformatics tools. The gene expression Omnibus (GEO) database was used to obtain next generation sequencing data (GSE270484) of T1DM and normal control samples. Furthermore, differentially expressed genes (DEGs) were screened using the DESeq2 package in R bioconductor package. Gene Ontology (GO) and pathway enrichment analyses were performed by g:Profiler. The protein–protein interaction (PPI) network was plotted with IID PPI database and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC. Then, microRNAs (miRNAs) and transcription factors (TFs) in T1DM were screened out from the miRNet and NetworkAnalyst database. Then, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed by Cytoscape software. Moreover, a drug-hub gene interaction network of the hub genes was constructed and predicted the drug molecule against hub genes. The receiver operating characteristic (ROC) curves were generated to predict diagnostic value of hub genes. Finally we performed molecular docking, ADMET profiling and molecular dynamics simulation studies of marine derived chemical constituents using Schrodinger Suite 2025-1. A total of 958 DEGs were screened: 479 up regulated genes and 479 down regulated genes. DEG were mainly enriched in the terms of developmental process, membrane, cation binding, response to stimulus, cell periphery, ion binding, neuronal system and metabolism. Based on the data of protein–protein interaction (PPI), the top 10 hub genes (5 up regulated and 5 down regulated) were ranked, including FN1, GSN, ADRB2, CEP128, FLNA, CD74, EFEMP2, POU6F2, P4HA2 and BCL6. The miRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-657, hsa-miR-1266-5p, NOTCH1 and GTF3C2 might play an important role in the pathogenesis of T1DM. The drug-hub gene interaction network showed that Clenbuterol, Diethylstilbestrol, Selegiline and Isoflurophate predicted therapeutic drugs for the T1DM. Molecular docking and molecular dynamics simulation study revealed that CMNPD5805 and CMNPD30286 as potential inhibitors of FN1 (pdb id: 3M7P) a key biomarker in pathogenesis of T1DM. These findings promote the understanding of the molecular mechanism and clinically related molecular targets for T1DM.