论文标题
从细胞反应到多个提示的信号传导机制检测
Detection of signaling mechanisms from cellular responses to multiple cues
论文作者
论文摘要
细胞信号网络是复杂的，并且通常不完全表征，因此很难获得它们编码的机制的全面图片。这些网络的数学建模提供了重要的线索，但是模型本身通常很复杂，并且并不总是清楚如何提取可伪造的预测。在这里，我们采用一个反向方法，使用细胞级别的实验数据来{推断}最小信号网络。我们专注于细胞对多个提示的响应，特别是在响应是拮抗的令人惊讶的情况下：对多个提示的响应比对单个提示的响应弱。我们使用（i）上调节或下调，（ii）分子转换或（iii）可逆结合的无处不在的成分，系统地构建一个节点一个节点。在每种情况下，我们的方法都揭示了一种最小，可解释的信号传导机制，该机制解释了拮抗反应。我们的工作提供了一种从细胞级数据推导{}分子机制的系统方法。
Cell signaling networks are complex and often incompletely characterized, making it difficult to obtain a comprehensive picture of the mechanisms they encode. Mathematical modeling of these networks provides important clues, but the models themselves are often complex, and it is not always clear how to extract falsifiable predictions. Here we take an inverse approach, using experimental data at the cell level to {deduce} the minimal signaling network. We focus on cells' response to multiple cues, specifically on the surprising case in which the response is antagonistic: the response to multiple cues is weaker than the response to the individual cues. We systematically build candidate signaling networks one node at a time, using the ubiquitous ingredients of (i) up- or down-regulation, (ii) molecular conversion, or (iii) reversible binding. In each case, our method reveals a minimal, interpretable signaling mechanism that explains the antagonistic response. Our work provides a systematic way to {deduce} molecular mechanisms from cell-level data.
