Differential Expression Analysis for Pathways

Life science technologies generate a deluge of data that hold the keys to unlocking the secrets of important biological functions and disease mechanisms. We present DEAP, Differential Expression Analysis for Pathways, which capitalizes on information about biological pathways to identify important regulatory patterns from differential expression data. DEAP makes significant improvements over existing approaches by including information about pathway structure and discovering the most differentially expressed portion of the pathway. On simulated data, DEAP significantly outperformed traditional methods: with high differential expression, DEAP increased power by two orders of magnitude; with very low differential expression, DEAP doubled the power. DEAP performance was illustrated on two different gene and protein expression studies. DEAP discovered fourteen important pathways related to chronic obstructive pulmonary disease and interferon treatment that existing approaches omitted. On th...生命科学技术可产生海量数据，这些数据正是解锁重要生物学功能与疾病机制奥秘的核心密钥。我们在此提出DEAP（Differential Expression Analysis for Pathways，通路差异表达分析），该工具依托生物学通路相关信息，从差异表达数据中识别关键调控模式。相较于现有方法，DEAP通过整合通路结构信息，并挖掘通路中差异表达最为显著的区段，实现了显著性能提升。在模拟数据集上，DEAP的表现显著优于传统方法：当差异表达程度较高时，DEAP的检验效能提升了两个数量级；当差异表达程度极低时，DEAP的检验效能提升一倍。我们通过两项独立的基因与蛋白质表达研究，验证了DEAP的性能表现。DEAP成功挖掘出了现有方法遗漏的、与慢性阻塞性肺疾病及干扰素治疗相关的14条关键通路。在……