Integrative analysis of protein-coding genes, long non-coding genes, and microRNAs in breast cancer by GDC RNATOOLS and drug-gene interaction analysis

Introduction: For this study, all mRNAs (Gene Expression Quantification (and microRNAs (BCGSCmiRNA Profiling) count matrix (۱۲۰۴ samples and ۶۰۴۸۳genes for mRNAs and ۱۱۸۲ samples and ۲۵۸۸genesfor microRNAs) data for breast cancer (the primary tumor) get from TCGA by GDC client after thatnormalized by TMM method and finding out differential express genes by Deseq۲ package. Volcano plotand bar plot and Hierarchical clustering are used to visualize DEGS analysis results.For ceRNAs network analysis of internally incorporated databases of miRNA-mRNA and miRNA-lncRNAinteractions are used. lncRNA-miRNA-mRNA interactions reported and visualized in Cytoscape. ForFunctional enrichment analysis, perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Disease Ontology (DO) on the list of DEGs.To find drug-gene interaction, by using DGIdb, selected (up and downregulated) gene in DEG file withcriteria (logFC>۲ and adjP.Val >۰.۰۰۵) for up-regulated and (logFC<-۲ and adjP.Val >۰.۰۰۵) for thedownregulated gene) and the results used as input for the DGIdb database. Then the interactions betweendrugs and differential express genes and the list of interactions are used as input to generate a network ofgenes and drugs.Results: Based on analysis ۱۷۶۳ differential express genes find out in breast cancer which among them ۱۵۱۴are protein-coding, ۱۹۱ are lncRNAs and noncoding RNAs, and ۴۷ pseudogenes and ۴ TR and ۷ TEC gensand ۲ IG genes. Based on ceRNAs network analysis finding ۴۰۴ miRNAs sponges by ۴۰۴ lncRNAs, and ۴۰۴miRNAs directly interact with ۴۰۴ mRNAs.Drug -gene interaction prediction by DGIdb: based on the filter that is set on DEGs, find ۶۰۶ downregulatedgenes that interact with the same number of drugs such as HRITONAVIREPARIN, CISPLATIN,RITONAVIR, etc. and ۷۳ upregulated genes interact with the same numbers of drugs such asMETHOTREXATE, TRASTUZUMAB, and so on.

کلیدواژه ها:

GDCRNA ، lncRNAs ، circulating RNA ، breast cancer ، drug-gene interaction ، DGIdb