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Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts
Published on: May 11, 2018
Single-cell sequencing and machine learning-based prediction of spliceosome-associated factor 2 may represent
Baihui Yang1, Xiangde Li2, Yiji Su3,4
1The First Clinical Medical College, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi, China.
Background:
Osteoarthritis has become a global health challenge due to its complex pathologic mechanisms. Spliceosome-associated factor 2 (SYF2) has been reported in tumors and neurological diseases, but not in studies of osteoarthritis. We employed single-cell sequencing and machine learning techniques to predict SYF2 as a potential therapeutic target for osteoarthritis and the underlying mechanisms involved.
Methods:
Single-cell dataset (GSE220243), cartilage tissue gene expression profiles (GSE169077, GSE117999, GSE53857) and blood sample expression profile (GSE48556) were obtained. We combined single-cell sequencing analysis and machine learning to sort candidate targets for osteoarthritis. We used GSEA analysis to predict the mechanisms of core target for osteoarthritis, and ultimately established osteoarthritis animal models to validate the screened targets.
Results:
Bioinformatics screening revealed a negative association between SYF2 and osteoarthritis. GSEA analysis showed that SYF2 negatively correlated with apoptosis. After establishing an osteoarthritis animal model, relative mRNA and protein expression levels were measured, consistent with the bioinformatics prediction results.
Conclusions:
Our research identified a previously unreported potential target for osteoarthritis, SYF2, through single-cell sequencing and machine learning. This target is likely to be related to cell apoptosis.
Insights
Spliceosome-associated factor 2 (SYF2) is a novel potential therapeutic target for osteoarthritis. This study found SYF2 is negatively associated with osteoarthritis and may regulate apoptosis, offering new insights for treatment.
Area of Science:
- Biomedical research
- Genomics
- Molecular biology
Background:
- Osteoarthritis (OA) presents a global health challenge with complex pathology.
- Spliceosome-associated factor 2 (SYF2) has been implicated in tumors and neurological diseases, but its role in OA is unexplored.
Purpose of the Study:
- To identify novel therapeutic targets for osteoarthritis using advanced bioinformatics.
- To investigate the potential role of SYF2 in osteoarthritis pathogenesis and its underlying mechanisms.
Main Methods:
- Utilized single-cell sequencing data (GSE220243) and gene expression profiles (GSE169077, GSE117999, GSE53857, GSE48556).
- Applied machine learning and Gene Set Enrichment Analysis (GSEA) to identify and analyze candidate targets.
- Validated findings through the establishment of osteoarthritis animal models.
Main Results:
- Bioinformatics screening identified a negative association between SYF2 and osteoarthritis.
- GSEA indicated that SYF2 negatively correlates with apoptosis.
- In vivo experiments confirmed the bioinformatics predictions regarding SYF2 expression.
Conclusions:
- Identified SYF2 as a novel potential therapeutic target for osteoarthritis.
- SYF2's mechanism in osteoarthritis may involve the regulation of cell apoptosis.
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