论文标题

细胞周期和蛋白质复杂动力学发现信号通路

Cell cycle and protein complex dynamics in discovering signaling pathways

论文作者

Inostroza, Daniel, Hernández, Cecilia, Seco, Diego, Navarro, Gonzalo, Olivera-Nappa, Alvaro

论文摘要

信号传导途径负责调节细胞过程,例如监视外部环境,跨膜传输信息以及做出细胞命运决策。鉴于可用的生物数据量增加,并且最近发现的发现,许多疾病与细胞信号转导级联反应的破坏有关,在硅细胞发现细胞生物学中的信号传导途径中,在过去几年中已成为一个活跃的研究主题。但是,信号通路的重建仍然是一个挑战,主要是因为需要系统的方法来预测因果关系,例如边缘方向和信号流中相互作用蛋白之间的激活/抑制。我们提出了一种预测信号通路的方法,以整合蛋白质相互作用,基因表达,表型和蛋白质复杂信息。我们的方法首先使用基于基于边缘的算法找到候选途径,然后定义图模型,以使用细胞周期基因表达和表型在候选途径中包括蛋白质之间的因果激活关系,以推断酵母中的一致途径。然后,我们结合了蛋白质复合物覆盖信息,以确定最终预测的信号通路。我们表明,我们的方法使用不同的排名指标改善了最新现状的预测结果。

Signaling pathways are responsible for the regulation of cell processes, such as monitoring the external environment, transmitting information across membranes, and making cell fate decisions. Given the increasing amount of biological data available and the recent discoveries showing that many diseases are related to the disruption of cellular signal transduction cascades, in silico discovery of signaling pathways in cell biology has become an active research topic in past years. However, reconstruction of signaling pathways remains a challenge mainly because of the need for systematic approaches for predicting causal relationships, like edge direction and activation/inhibition among interacting proteins in the signal flow. We propose an approach for predicting signaling pathways that integrates protein interactions, gene expression, phenotypes, and protein complex information. Our method first finds candidate pathways using a directed-edge-based algorithm and then defines a graph model to include causal activation relationships among proteins, in candidate pathways using cell cycle gene expression and phenotypes to infer consistent pathways in yeast. Then, we incorporate protein complex coverage information for deciding on the final predicted signaling pathways. We show that our approach improves the predictive results of the state of the art using different ranking metrics.

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