Integrative Meta-Analysis of Huntington's Disease Transcriptome Landscape.
Nela Pragathi SnehaS Akila Parvathy DharshiniY-H TaguchiM Michael GromihaPublished in: Genes (2022)
Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance caused by glutamine expansion in the Huntingtin gene (HTT). Striatal projection neurons (SPNs) in HD are more vulnerable to cell death. The executive striatal population is directly connected with the Brodmann Area (BA9), which is mainly involved in motor functions. Analyzing the disease samples from BA9 from the SRA database provides insights related to neuron degeneration, which helps to identify a promising therapeutic strategy. Most gene expression studies examine the changes in expression and associated biological functions. In this study, we elucidate the relationship between variants and their effect on gene/downstream transcript expression. We computed gene and transcript abundance and identified variants from RNA-seq data using various pipelines. We predicted the effect of genome-wide association studies (GWAS)/novel variants on regulatory functions. We found that many variants affect the histone acetylation pattern in HD, thereby perturbing the transcription factor networks. Interestingly, some variants affect miRNA binding as well as their downstream gene expression. Tissue-specific network analysis showed that mitochondrial, neuroinflammation, vasculature, and angiogenesis-related genes are disrupted in HD. From this integrative omics analysis, we propose that abnormal neuroinflammation acts as a two-edged sword that indirectly affects the vasculature and associated energy metabolism. Rehabilitation of blood-brain barrier functionality and energy metabolism may secure the neuron from cell death.
Keyphrases
- copy number
- rna seq
- single cell
- gene expression
- mitochondrial dna
- cell death
- dna methylation
- blood brain barrier
- network analysis
- genome wide
- transcription factor
- systematic review
- poor prognosis
- cerebral ischemia
- case control
- genome wide association
- traumatic brain injury
- genome wide identification
- binding protein
- lipopolysaccharide induced
- working memory
- dna binding
- lps induced
- big data
- oxidative stress
- cell cycle arrest
- endothelial cells
- machine learning
- long non coding rna
- spinal cord injury
- brain injury
- cell proliferation
- meta analyses
- microbial community
- wastewater treatment
- wound healing
- randomized controlled trial
- adverse drug
- diffusion weighted imaging
- subarachnoid hemorrhage