arXiv:2409.05047q-bio.GNcs.LG2024-09被引 1

用机器学习找与眼底疤痕严重程度相关的关键基因,助力老年黄斑变性治疗靶点发现。

Machine Learning-Based Prediction of Key Genes Correlated to the Subretinal Lesion Severity in a Mouse Model of Age-Related Macular Degeneration

  • 基于通路降维与基因扩增的特征工程提升预测精度
  • 识别出多个与病变严重程度强相关的候选基因
  • 为老年黄斑变性药物研发提供潜在靶点,适合眼科与生物信息研究者

老年黄斑变性(AMD)是老年人失明的主要原因,严重损害视力与生活质量。尽管对AMD的认识不断深入,但驱动视网膜下纤维化病变严重程度的分子机制仍不明确,阻碍了有效疗法的发展。本研究提出一种基于机器学习的框架,用于预测与病变严重程度密切相关的关键基因,并识别潜在治疗靶点以预防视网膜下纤维化。利用来自JR5558小鼠病理性视网膜的原始RNA-seq数据,我们开发了一种新颖且特定的特征工程方法,包括基于通路的降维和基于基因的特征扩展,以提高预测准确性。通过迭代使用Ridge与ElasticNet回归模型,评估了基因的生物学相关性和影响。结果揭示了多个关键基因的生物学意义,并证明该框架在识别新治疗靶点方面的有效性。研究结果为推进药物研发和改善AMD治疗策略提供了重要洞见,有望通过靶向视网膜下病变的遗传机制提升患者预后。

原文摘要 · Abstract (English)

Age-related macular degeneration (AMD) is a major cause of blindness in older adults, severely affecting vision and quality of life. Despite advances in understanding AMD, the molecular factors driving the severity of subretinal scarring (fibrosis) remain elusive, hampering the development of effective therapies. This study introduces a machine learning-based framework to predict key genes that are strongly correlated with lesion severity and to identify potential therapeutic targets to prevent subretinal fibrosis in AMD. Using an original RNA sequencing (RNA-seq) dataset from the diseased retinas of JR5558 mice, we developed a novel and specific feature engineering technique, including pathway-based dimensionality reduction and gene-based feature expansion, to enhance prediction accuracy. Two iterative experiments were conducted by leveraging Ridge and ElasticNet regression models to assess biological relevance and gene impact. The results highlight the biological significance of several key genes and demonstrate the framework's effectiveness in identifying novel therapeutic targets. The key findings provide valuable insights for advancing drug discovery efforts and improving treatment strategies for AMD, with the potential to enhance patient outcomes by targeting the underlying genetic mechanisms of subretinal lesion development.

机器学习基因预测黄斑变性生物信息

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