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PPISURV:一种用于揭示特定基因在癌症生存结果中隐藏作用的新型生物信息学工具。

PPISURV: a novel bioinformatics tool for uncovering the hidden role of specific genes in cancer survival outcome.

机构信息

1] Toxicology Unit, Hodgkin Building, Medical Research Council, Leicester University, Leicester, UK [2] Molecular Pharmacology Laboratory, Technological University, St-Petersburg, Russia.

Institute for Molecular Medicine Finland FIMM, University of Helsinki; Helsinki, Finland.

出版信息

Oncogene. 2014 Mar 27;33(13):1621-8. doi: 10.1038/onc.2013.119. Epub 2013 May 20.

Abstract

Multiple clinical studies have correlated gene expression with survival outcome in cancer on a genome-wide scale. However, in many cases, no obvious correlation between expression of well-known tumour-related genes (that is, p53, p73 and p21) and survival rates of patients has been observed. This can be mainly explained by the complex molecular mechanisms involved in cancer, which mask the clinical relevance of a gene with multiple functions if only gene expression status is considered. As we demonstrate here, in many such cases, the expression of the gene interaction partners (gene 'interactome') correlates significantly with cancer survival and is indicative of the role of that gene in cancer. On the basis of this principle, we have implemented a free online datamining tool (http://www.bioprofiling.de/PPISURV). PPISURV automatically correlates expression of an input gene interactome with survival rates on >40 publicly available clinical expression data sets covering various tumours involving about 8000 patients in total. To derive the query gene interactome, PPISURV employs several public databases including protein-protein interactions, regulatory and signalling pathways and protein post-translational modifications.

摘要

多项临床研究已经在全基因组范围内将基因表达与癌症的生存结果相关联。然而,在许多情况下,并未观察到众所周知的肿瘤相关基因(即 p53、p73 和 p21)的表达与患者生存率之间存在明显的相关性。这主要可以归因于癌症中涉及的复杂分子机制,如果仅考虑基因表达状态,则会掩盖具有多种功能的基因的临床相关性。正如我们在这里所证明的那样,在许多此类情况下,基因相互作用伙伴(基因“相互作用组”)的表达与癌症的生存显著相关,并且表明该基因在癌症中的作用。基于这一原理,我们已经实现了一个免费的在线数据挖掘工具(http://www.bioprofiling.de/PPISURV)。PPISURV 自动将输入基因相互作用组的表达与 >40 个公开可用的临床表达数据集的生存率相关联,这些数据集总共涵盖了涉及约 8000 名患者的各种肿瘤。为了得出查询基因相互作用组,PPISURV 利用了包括蛋白质-蛋白质相互作用、调控和信号通路以及蛋白质翻译后修饰在内的几个公共数据库。

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