Department of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong 250061, China.
Department of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong 250061, China.
J Biomed Inform. 2018 Jun;82:143-153. doi: 10.1016/j.jbi.2018.05.006. Epub 2018 May 12.
Gene expression profiling techniques measure the transcriptional dynamics of thousands of genes in parallel manners. The available high-throughput transcriptomic datasets provide unprecedented opportunities of detecting biomarkers or signatures of complex diseases such as diabetes. In this work, we propose a computational method based on differential entropy to identify diabetic pathway biomarkers in rats from gene expression profiling data. We first collect the knowledgebase-documented pathways and map them with the corresponding gene expressions in control and disease samples, respectively. The pathway entropies are defined to evaluate their dysfunction-related activities and implications during the development and progression of type 2 diabetes. We rank these pathways via their differential status of entropy dynamics in the time series. The pathway biomarkers are then screened out by their classification ability of distinguishing diabetes from controls. The comparative studies with the other alternative methods demonstrate the effectiveness and advantage of our proposed strategy of biomarker identification. The classification performances on independent datasets further validate the diagnosis applicability of these identified pathway biomarkers. The functional enrichment analyses of these pathway biomarkers also indicate the pathogenesis of diabetes.
基因表达谱技术以并行方式测量数千个基因的转录动态。现有的高通量转录组数据集提供了检测生物标志物或复杂疾病（如糖尿病）特征的前所未有的机会。在这项工作中，我们提出了一种基于差分熵的计算方法，用于从基因表达谱数据中识别大鼠的糖尿病通路生物标志物。我们首先收集知识库记录的途径，并分别将其与对照和疾病样本中的相应基因表达映射。定义途径熵以评估它们在 2 型糖尿病的发生和发展过程中的与功能障碍相关的活性和影响。我们通过它们在时间序列中熵动态的差异状态对这些途径进行排名。然后通过区分糖尿病与对照的分类能力筛选出途径生物标志物。与其他替代方法的比较研究证明了我们提出的生物标志物识别策略的有效性和优势。在独立数据集上的分类性能进一步验证了这些鉴定的途径生物标志物的诊断适用性。这些途径生物标志物的功能富集分析也表明了糖尿病的发病机制。
