Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions.
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DOI：
10.1371/journal.pone.0251399
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Bozdag S
中科院分区：
文献类型：
--
作者：
Kesimoglu ZN;Bozdag S
为了了解癌症等复杂疾病的驱动生物学因素，需要发现基因的调控回路。近年来，人们发现了一种新的基因调控机制，即竞争性内源性RNA （competing endogenous RNA, ceRNA）相互作用。被普通microrna （miRNA）靶向的某些基因“竞争”这些microrna，从而通过使其他基因不受miRNA的调节而相互调节。已经发布了一些计算工具来推断ceRNA网络。然而，在大多数现有的工具中，没有考虑cerna的表达丰度充足性、集体调控和群体效应。在这项研究中，我们开发了一个名为Crinet的计算工具来推断全基因组的ceRNA网络，以解决关键缺陷。Crinet认为所有mrna、lncRNAs和假基因都是潜在的ceRNA，并采用网络反卷积方法来排除虚假的ceRNA对。我们用TCGA的乳腺癌数据测试了Crinet。Crinet推断出可重复的ceRNA相互作用和组，这些相互作用和组在癌症相关基因和过程中显著富集。我们用基于蛋白质表达的基准验证了所选择的mirna -靶标相互作用，并在敲低实验中评估了推断的预测基因表达变化的ceRNA相互作用。推断出的ceRNA网络中的枢纽基因包括乳腺癌中已知的抑制基因/癌基因lncrna，这表明非编码RNA的包含对ceRNA推断的重要性。crinet推断的ceRNA组一直参与免疫系统相关过程，在证实免疫治疗与癌症之间关系的研究中可能是重要的资产。Crinet的源代码是R语言的，可以在https://github.com/bozdaglab/crinet上获得。
To understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) “compete” for these miRNAs, thereby regulate each other by making others free from miRNA regulation. Several computational tools have been published to infer ceRNA networks. In most existing tools, however, expression abundance sufficiency, collective regulation, and groupwise effect of ceRNAs are not considered. In this study, we developed a computational tool named Crinet to infer genome-wide ceRNA networks addressing critical drawbacks. Crinet considers all mRNAs, lncRNAs, and pseudogenes as potential ceRNAs and incorporates a network deconvolution method to exclude the spurious ceRNA pairs. We tested Crinet on breast cancer data in TCGA. Crinet inferred reproducible ceRNA interactions and groups, which were significantly enriched in the cancer-related genes and processes. We validated the selected miRNA-target interactions with the protein expression-based benchmarks and also evaluated the inferred ceRNA interactions predicting gene expression change in knockdown assays. The hub genes in the inferred ceRNA network included known suppressor/oncogene lncRNAs in breast cancer showing the importance of non-coding RNA’s inclusion for ceRNA inference. Crinet-inferred ceRNA groups that were consistently involved in the immune system related processes could be important assets in the light of the studies confirming the relation between immunotherapy and cancer. The source code of Crinet is in R and available at https://github.com/bozdaglab/crinet.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
关于癌症基因组地图集的泛伴奏蛋白质组学观点。
影响因子：
16.6
作者：
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通讯作者：
Mills, Gordon B.
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
胶质母细胞瘤的差异相关分析揭示了可预测患者生存的免疫 ceRNA 相互作用。
影响因子：
3
作者：
Chiu YC;Wang LJ;Lu TP;Hsiao TH;Chuang EY;Chen Y
通讯作者：
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CERNA假设：隐藏RNA语言的Rosetta石头？
影响因子：
64.5
作者：
Salmena L;Poliseno L;Tay Y;Kats L;Pandolfi PP
通讯作者：
Pandolfi PP