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A New Method for Discovering Disease-Specific MiRNA-Target Regulatory Networks

机译:发现特定疾病的miRNA-靶标调控网络的新方法

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摘要

Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs) are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA - targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the?miRablemethod whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal?miRable?follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools) and pathology specific data (gene expression data). A case study on Prostate Cancer has shown that?miRable?is able to: 1) find new potential miRNA-targets pairs, 2) highlight novel genes potentially involved in a disease but never or little studied before, 3) reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.
机译:基因及其表达调控是理解复杂疾病发生和发展的关键因素。在这种情况下,microRNA(miRNA)是转录后调节因子,在基因表达中起着重要作用,因为它们在诸如心血管疾病和癌症的病理中经常被失调。 miRNA的体外验证-靶标调控通常过于昂贵且费时,无法针对每种可能的替代方法进行。结果,迫切需要能够提供一些标准以对试验进行优先排序的工具。此外,在计划进行体外实验之前,科学家需要评估miRNA-靶基因的相互作用网络。在本文中,我们描述了miRable方法,其目的是识别新的潜在相关基因及其相互作用网络与特定病理学相关。为了实现这一目标,“可行”遵循一种系统生物学方法,将通用医学知识(文学,蛋白质-蛋白质相互作用网络,预测工具)和病理学特定数据(基因表达数据)整合在一起。一项针对前列腺癌的案例研究表明,“ miRable”能够:1)找到新的潜在miRNA-靶标对,2)突出显示可能与疾病有关但从未研究或很少研究的新基因,3)重建所有可能的调控子网从文献开始,以扩展有关miRNA调控机制调控的知识。

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