摘要
背景：自噬和细胞凋亡是清除衰老和突变的细胞成分甚至整个细胞的细胞中的基本生理过程。在大多数主要疾病，例如癌症和神经系统疾病中，自噬和细胞凋亡均被破坏。近来，由于自噬和细胞凋亡在几种病理过程中紧密协同或相反的功能，人们越来越重视了解自噬和细胞凋亡之间的串扰。 目的：本研究旨在协助自噬和凋亡相关药物的研究，阐明两个过程之间的密切和复杂的联系，并为新药开发提供指导。 方法：我们建立了两个专门针对自噬和细胞凋亡的化学基因组数据库，包括自噬和细胞凋亡相关的蛋白质，途径和化合物。然后，我们对凋亡相关蛋白和自噬相关蛋白进行了网络分析，并首次研究了这两个紧密相连过程的全蛋白-蛋白相互作用（PPI）网络。 结果：我们发现的重叠靶标彼此之间的联系比完整网络中的其他靶标更紧密，这表明药物调制具有更高的疗效潜力。我们还发现，死亡相关蛋白激酶1（DAPK1）是连接自噬和细胞凋亡相关途径（超出重叠部分）的关键点，这一发现可能揭示了该过程的一些微妙信号机制。最后，我们演示了如何在计算机靶标识别中利用我们的集成计算化学基因组学工具来鉴定能够调节自噬和凋亡相关途径的小分子。 结论：凋亡和自噬的知识库和集成工具将加快我们在自噬和凋亡相关研究中的工作，并可为信息搜索，靶标预测和新化学发现提供有用的资源。
关键词: 自噬，细胞凋亡，癌症，神经系统疾病，系统药理，网络分析。
图形摘要
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