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推断信号通路中基因表达变化的功能效应。

Inferring the functional effect of gene expression changes in signaling pathways.

机构信息

Department of Computational Genomics, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain.

出版信息

Nucleic Acids Res. 2013 Jul;41(Web Server issue):W213-7. doi: 10.1093/nar/gkt451. Epub 2013 Jun 8.

DOI:10.1093/nar/gkt451
PMID:23748960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3692130/
Abstract

Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case-control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/.

摘要

信号通路是一种有价值的信息来源,可以解释基因活性的改变如何影响特定的细胞功能。有一些网络工具可以用来查看和编辑通路,并在其上表示实验数据。然而,很少有方法旨在识别与所研究的生物学问题相关的信号通路,而且它们都没有提供方便的图形化网络界面。我们提出了 PATHiWAYS,这是一个基于网络的信号通路可视化系统,它可以从典型的表达微阵列病例对照实验中基因表达值的测量中推断出影响细胞功能的信号通路的变化。该系统使用通路的简单概率模型来估计从任何受体到任何最终效应分子的信号传递概率(考虑到通路拓扑结构),为此,我们使用从基因表达值推断出的基因产物存在/不存在的个体概率。这些概率的显著变化可以将通路触发的不同细胞功能与所研究的生物学问题联系起来。PATHiWAYS 可在以下网址获得:http://pathiways.babelomics.org/。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b6/3692130/1c66c533bcbf/gkt451f1p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b6/3692130/1c66c533bcbf/gkt451f1p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b6/3692130/1c66c533bcbf/gkt451f1p.jpg

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