A least angle regression model for the prediction of canonical and non-canonical miRNA-mRNA interactions.
A least angle regression model for the prediction of canonical and non-canonical miRNA-mRNA interactions.
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DOI：
10.1371/journal.pone.0040634
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Spang R
中科院分区：
文献类型：
--
作者：
Engelmann JC;Spang R
MicroRNAs(MiRNAs)是一种短的非编码RNA，在细胞分化、发育和致癌转化等多种生物学过程中具有调节功能。它们可以与蛋白质编码基因的mRNA转录结合，抑制它们的翻译或导致mRNA降解。相反，miRNAs的转录受信号通路中的转录因子、辅助因子和信使分子等蛋白质的调控，形成了一个基因和miRNA表达的双向调控网络。在这里，我们描述了一种基于配对基因和miRNA表达谱的最小角度回归方法，用于揭示基因和miRNA调控的功能相互作用。首先，我们证明确实可以从被预测为调节特定基因的miRNAs的表达谱中重建基因表达谱。其次，我们提出了一个两步模型，在第一步中，序列信息被用来约束可能的调节miRNAs集，在第二步，这个约束被放松以找到不依赖于完美种子结合的调节miRNAs。最后，根据我们之前的调控预测，构建了由miRNAs调控基因和miRNAs调控基因组成的双向网络。在将该方法应用于人类癌细胞系数据集后，对潜在网络的分析显示，当调控异常时，已知与癌症相关的miRNAs是具有凋亡功能的基因的预测因子。在预测和新发现的靶点中，缺少一个特定的oncomiR-19b-1的经典miRNA种子结合位点，我们发现了与凋亡相关的基因的过度表达，这与先前的发现一致，即该miRNA是mir-17-92簇中的关键致癌因子。此外，我们发现了与DNA重组和修复有关的基因，这些基因强调了DNA重组在维持细胞完整性方面的重要性。
microRNAs (miRNAs) are short non-coding RNAs with regulatory functions in various biological processes including cell differentiation, development and oncogenic transformation. They can bind to mRNA transcripts of protein-coding genes and repress their translation or lead to mRNA degradation. Conversely, the transcription of miRNAs is regulated by proteins including transcription factors, co-factors, and messenger molecules in signaling pathways, yielding a bidirectional regulatory network of gene and miRNA expression. We describe here a least angle regression approach for uncovering the functional interplay of gene and miRNA regulation based on paired gene and miRNA expression profiles. First, we show that gene expression profiles can indeed be reconstructed from the expression profiles of miRNAs predicted to be regulating the specific gene. Second, we propose a two-step model where in the first step, sequence information is used to constrain the possible set of regulating miRNAs and in the second step, this constraint is relaxed to find regulating miRNAs that do not rely on perfect seed binding. Finally, a bidirectional network comprised of miRNAs regulating genes and genes regulating miRNAs is built from our previous regulatory predictions. After applying the method to a human cancer cell line data set, an analysis of the underlying network reveals miRNAs known to be associated with cancer when dysregulated are predictors of genes with functions in apoptosis. Among the predicted and newly identified targets that lack a classical miRNA seed binding site of a specific oncomir, miR-19b-1, we found an over-representation of genes with functions in apoptosis, which is in accordance with the previous finding that this miRNA is the key oncogenic factor in the mir-17-92 cluster. In addition, we found genes involved in DNA recombination and repair that underline its importance in maintaining the integrity of the cell.
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影响因子：
14.9
作者：
Anders G;Mackowiak SD;Jens M;Maaskola J;Kuntzagk A;Rajewsky N;Landthaler M;Dieterich C
通讯作者：
Dieterich C
影响因子：
12.3
作者：
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通讯作者：
Zhang J
影响因子：
5.7
作者：
Blower, Paul E.;Verducci, Joseph S.;Sadee, Wolfgang
通讯作者：
Sadee, Wolfgang
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.