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MECoRank:同时评估 SNVs 和差异表达对转录网络影响的癌症驱动基因发现。

MECoRank: cancer driver genes discovery simultaneously evaluating the impact of SNVs and differential expression on transcriptional networks.

机构信息

Key Lab of Intelligent Computing and Signal Processing of Ministry of Education, College of Computer Science and Technology, Anhui University, Hefei, China.

Institute of Physical Science and Information Technology, Anhui University, Hefei, China.

出版信息

BMC Med Genomics. 2019 Dec 30;12(Suppl 7):140. doi: 10.1186/s12920-019-0582-8.

Abstract

BACKGROUND

Although there are huge volumes of genomic data, how to decipher them and identify driver events is still a challenge. The current methods based on network typically use the relationship between genomic events and consequent changes in gene expression to nominate putative driver genes. But there may exist some relationships within the transcriptional network.

METHODS

We developed MECoRank, a novel method that improves the recognition accuracy of driver genes. MECoRank is based on bipartite graph to propagates the scores via an iterative process. After iteration, we will obtain a ranked gene list for each patient sample. Then, we applied the Condorcet voting method to determine the most impactful drivers in a population.

RESULTS

We applied MECoRank to three cancer datasets to reveal candidate driver genes which have a greater impact on gene expression. Experimental results show that our method not only can identify more driver genes that have been validated than other methods, but also can recognize some impactful novel genes which have been proved to be more important in literature.

CONCLUSIONS

We propose a novel approach named MECoRank to prioritize driver genes based on their impact on the expression in the molecular interaction network. This method not only assesses mutation's effect on the transcriptional network, but also assesses the differential expression's effect within the transcriptional network. And the results demonstrated that MECoRank has better performance than the other competing approaches in identifying driver genes.

摘要

背景

尽管有大量的基因组数据,但如何解读这些数据并识别驱动事件仍然是一个挑战。目前基于网络的方法通常利用基因组事件与基因表达变化之间的关系来提名潜在的驱动基因。但转录网络内部可能存在一些关系。

方法

我们开发了 MECoRank 方法,该方法可以提高驱动基因识别的准确性。MECoRank 基于二分图,通过迭代过程传播分数。迭代后,我们将为每个患者样本获得一个基因排名列表。然后,我们应用 Condorcet 投票方法来确定群体中最具影响力的驱动基因。

结果

我们将 MECoRank 应用于三个癌症数据集,以揭示对基因表达影响更大的候选驱动基因。实验结果表明,与其他方法相比,我们的方法不仅可以识别出更多已验证的驱动基因,还可以识别出一些在文献中已被证明更重要的有影响力的新基因。

结论

我们提出了一种名为 MECoRank 的新方法,用于根据它们对分子相互作用网络中表达的影响对驱动基因进行优先级排序。该方法不仅评估了突变对转录网络的影响,还评估了转录网络内差异表达的影响。结果表明,MECoRank 在识别驱动基因方面的性能优于其他竞争方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d703/6936061/eebc4c560bc1/12920_2019_582_Fig1_HTML.jpg

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