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Peer-reviewedCC BY-NC-ND 4.0IET Systems Biology

Bioinformatics Analysis to Reveal Potential Targets of Huntington's Disease

  1. 1Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
  2. 2Department of Cardiology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disease resulted from the expansion of CAG repeats in huntingtin (HTT) gene and characterised by motor impairment, psychiatric disorders and cognitive decline. Currently, there are no available disease‐modifying treatments. In this study, we performed an integrative analysis of HD datasets downloaded from the Gene Expression Omnibus (GEO) database using machine learning approaches, Mendelian randomisation (MR) and single cell RNA‐sequencing (scRNA‐seq) analysis to elucidate underlying disease mechanisms. The machine learning algorithms of LASSO, random forest and SVM‐RFE identified the decreased ADRA2A in HD. In addition, MR analysis revealed HD‐associated proteins such as LILRA4 and UBE2D1, associated with immune response and ubiquitination metabolism, respectively. scRNA‐seq analysis further identified the transcription factors of SOX4 and ETV1 through SCENIC analysis. Pseudotime trajectory analysis highlighted heparan sulphate sulfotransferase activity, involving genes CHST11, HS3ST3A1 and HS6ST3 that drive cell differentiation. Moreover, cell‐cell communication analysis demonstrated enhanced NRG1/3‐ERBB4 signalling pathway in HD. This study presents multiple potential targets for HD treatment but further experimental validation is required to confirm their functional relevance.

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BibTeX
@article{yang2026bioinformatics,
  title = {{Bioinformatics Analysis to Reveal Potential Targets of Huntington's Disease}},
  author = {Shu Yang and Xinjie Xu and Weida Liu and Shuyang Zhang},
  journal = {IET Systems Biology},
  year = {2026},
  month = nov,
  doi = {10.1049/syb2.70088},
  url = {https://doi.org/10.1049/syb2.70088},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Bioinformatics Analysis to Reveal Potential Targets of Huntington's Disease
AU  - Shu Yang
AU  - Xinjie Xu
AU  - Weida Liu
AU  - Shuyang Zhang
PY  - 2026
DA  - 2026/11/01
JO  - IET Systems Biology
DO  - 10.1049/syb2.70088
UR  - https://doi.org/10.1049/syb2.70088
AB  - Huntington's disease (HD) is a progressive neurodegenerative disease resulted from the expansion of CAG repeats in huntingtin (HTT) gene and characterised by motor impairment, psychiatric disorders and cognitive decline. Currently, there are no available disease‐modifying treatments. In this study, we performed an integrative analysis of HD datasets downloaded from the Gene Expression Omnibus (GEO) database using machine learning approaches, Mendelian randomisation (MR) and single cell RNA‐sequencing (scRNA‐seq) analysis to elucidate underlying disease mechanisms. The machine learning algorithms of LASSO, random forest and SVM‐RFE identified the decreased ADRA2A in HD. In addition, MR analysis revealed HD‐associated proteins such as LILRA4 and UBE2D1, associated with immune response and ubiquitination metabolism, respectively. scRNA‐seq analysis further identified the transcription factors of SOX4 and ETV1 through SCENIC analysis. Pseudotime trajectory analysis highlighted heparan sulphate sulfotransferase activity, involving genes CHST11, HS3ST3A1 and HS6ST3 that drive cell differentiation. Moreover, cell‐cell communication analysis demonstrated enhanced NRG1/3‐ERBB4 signalling pathway in HD. This study presents multiple potential targets for HD treatment but further experimental validation is required to confirm their functional relevance.
SN  - 1751-8849
SN  - 1751-8857
ER  -