统一调控的信号通路揭示了组织特异性的串扰，并为药物靶点的发现提供了支持。

Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery.

机构信息

Department of Genetics, Eötvös University, Budapest, Hungary.

出版信息

Bioinformatics. 2010 Aug 15;26(16):2042-50. doi: 10.1093/bioinformatics/btq310. Epub 2010 Jun 11.

DOI:10.1093/bioinformatics/btq310

PMID:20542890

Abstract

MOTIVATION

Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult.

RESULTS

We present SignaLink, a database containing eight major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster and humans. Based on 170 review and approximately 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the eight pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery.

CONCLUSIONS

We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease, and underscore its importance in network-based drug target selection.

AVAILABILITY

http://SignaLink.org.

摘要

动机

信号通路控制着大量的细胞过程。然而，即使在同一个数据库中，信号通路通常也会以不同的详细程度进行注释。这使得比较和串扰分析变得困难。

结果

我们介绍了 SignaLink，这是一个包含来自秀丽隐杆线虫、黑腹果蝇和人类的 8 种主要信号通路的数据库。基于 170 篇综述和大约 800 篇研究文章，我们通过半自动搜索和统一的、有充分记录的注释规则来构建途径。我们发现，在人类中，这 8 种途径中的任意两种都可以发生串扰。我们量化了串扰的可能组织和癌症特异性活性，并找到了途径特异性的表达谱。此外，我们还确定了 327 种与药物靶点发现相关的蛋白质。