Affiliation:
1. Statistics Discipline, Science, Engineering & Technology School, Khulna University, Khulna, Bangladesh
2. Biotechnology & Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh
3. Electronics and Communication Engineering Discipline, Khulna University, Khulna, Bangladesh
4. Department of Computer Science and Engineering, Islamic University, Kushtia, Bangladesh
Abstract
Huntington disease (HD) is a degenerative brain disease caused by the expansion of CAG (cytosine-adenine-guanine) repeats, which is inherited as a dominant trait and progressively worsens over time possessing threat. Although HD is monogenetic, the specific pathophysiology and biomarkers are yet unknown specifically, also, complex to diagnose at an early stage, and identification is restricted in accuracy and precision. This study combined bioinformatics analysis and network-based system biology approaches to discover the biomarker, pathways, and drug targets related to molecular mechanism of HD etiology. The gene expression profile data sets GSE64810 and GSE95343 were analyzed to predict the molecular markers in HD where 162 mutual differentially expressed genes (DEGs) were detected. Ten hub genes among them ( DUSP1, NKX2-5, GLI1, KLF4, SCNN1B, NPHS1, SGK2, PITX2, S100A4, and MSX1) were identified from protein-protein interaction (PPI) network which were mostly expressed as down-regulated. Following that, transcription factors (TFs)-DEGs interactions (FOXC1, GATA2, etc), TF-microRNA (miRNA) interactions (hsa-miR-340, hsa-miR-34a, etc), protein-drug interactions, and disorders associated with DEGs were predicted. Furthermore, we used gene set enrichment analysis (GSEA) to emphasize relevant gene ontology terms (eg, TF activity, sequence-specific DNA binding) linked to DEGs in HD. Disease interactions revealed the diseases that are linked to HD, and the prospective small drug molecules like cytarabine and arsenite was predicted against HD. This study reveals molecular biomarkers at the RNA and protein levels that may be beneficial to improve the understanding of molecular mechanisms, early diagnosis, as well as prospective pharmacologic targets for designing beneficial HD treatment.
Subject
Applied Mathematics,Computational Mathematics,Computer Science Applications,Molecular Biology,Biochemistry
Cited by
2 articles.
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