Shared interactions between MCF7 and MDA-MB-231 cells

PPIs commonly shared between two breast cancer cell lines (MCF7 and MDA-MB-231). PPIs from wild-type and mutant isoforms of each bait were combined. Baits are shown as yellow box, and preys as grey circle. Size of each node represents number of patients with alterations in each protein. Dotted line represents the physical protein-protein association (validated in other studies) with high Integrated Association Stringency score.
We developed a method for calculating a differential interaction score (DIS) and a corresponding false discovery rate (FDR) using AP-MS data across multiple cell lines. This approach uses the SAINTexpress score (Teo et al., 2014b) which is the probability of a PPI being bonafide in a single cell line computed using a mixture of distribution modeling spectral counts of true and false interactions. The probabilities based on the analysis of a single cell line can then be used to calculate a differential interaction score between PPIs present in cancer cells and normal cells. We define a cancer-specific differential interaction score as the probability of the PPI being present in a cancer cell line but absent in the normal cell line.

两种乳腺癌细胞系（MCF7与MDA-MB-231）共有的蛋白质-蛋白质相互作用（Protein-Protein Interaction，PPI）。将各诱饵蛋白的野生型与突变型同工型所对应的PPI进行合并。诱饵蛋白以黄色方框呈现，捕获蛋白以灰色圆形表示。每个节点的尺寸代表对应蛋白存在变异的患者数量。虚线代表经其他研究验证、且具有高整合关联严格性评分的物理性蛋白质-蛋白质相互作用。

我们开发了一种基于多细胞系的亲和纯化质谱（Affinity Purification-Mass Spectrometry，AP-MS）数据，用于计算差异相互作用评分（Differential Interaction Score，DIS）及其对应错误发现率（False Discovery Rate，FDR）的方法。该方法采用了SAINTexpress评分（Teo等，2014b），该评分通过对真实与虚假相互作用的谱计数进行分布混合建模，计算得到单个细胞系中PPI为真实相互作用的概率。基于单个细胞系分析得到的概率，可用于计算癌细胞与正常细胞中存在的PPI之间的差异相互作用评分。我们将癌症特异性差异相互作用评分定义为：某PPI存在于癌细胞系中，但在正常细胞系中不存在的概率。