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Understanding cooperativity of microRNAs via microRNA association networks.

Na YJ, Kim JH - BMC Genomics (2013)

Bottom Line: In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner.On the system level, we identified cooperatively regulating miRNAs in the miRNA association network.We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: MicroRNAs (miRNAs) are key components in post-transcriptional gene regulation in multicellular organisms. As they control cooperatively a large number of their target genes, they affect the complexity of gene regulation. One of the challenges to understand miRNA-mediated regulation is to identify co-regulating miRNAs that simultaneously regulate their target genes in a network perspective.

Results: We created miRNA association network by using miRNAs sharing target genes based on sequence complementarity and co-expression patterns of miRNA-target pairs. The degree of association between miRNAs can be assessed by the level of concordance between targets of miRNAs. Cooperatively regulating miRNAs have been identified by network topology-based approach. Cooperativity of miRNAs is evaluated by their shared transcription factors and functional coherence of target genes. Pathway enrichment analysis of target genes in the cooperatively regulating miRNAs revealed the mutually exclusive functional landscape of miRNA cooperativity. In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner. Sequence and structural similarity analysis within miRNA association network showed that pre-miRNA secondary structure may be involved in the expression of mature miRNA's function.

Conclusions: On the system level, we identified cooperatively regulating miRNAs in the miRNA association network. We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar. This study demonstrates the potential importance of the secondary structures of pre-miRNAs in both cooperativity and specificity of target genes.

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Comparison of enrichment scores of target genes between this study and previous study. We made (A) boxplot and (B) density plot in order to compare the distribution of enrichment scores of target genes between this study and previous study. These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study.
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Figure 5: Comparison of enrichment scores of target genes between this study and previous study. We made (A) boxplot and (B) density plot in order to compare the distribution of enrichment scores of target genes between this study and previous study. These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study.

Mentions: We used Wilcoxon Rank Sum test to compare target gene enrichment scores between this study and previous study. A statistically significant difference in the target gene enrichment score distribution was observed (p-value = 1.495e-06). In addition, in order to compare the distribution of enrichment scores of target genes between this study and previous study, we made boxplot and density plot (Figure 5(A,B)). These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study. In conclusion, we can demonstrate that our pipeline for finding miRNA modules is more efficient than previous method in terms of enrichment of target gene function.


Understanding cooperativity of microRNAs via microRNA association networks.

Na YJ, Kim JH - BMC Genomics (2013)

Comparison of enrichment scores of target genes between this study and previous study. We made (A) boxplot and (B) density plot in order to compare the distribution of enrichment scores of target genes between this study and previous study. These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852507&req=5

Figure 5: Comparison of enrichment scores of target genes between this study and previous study. We made (A) boxplot and (B) density plot in order to compare the distribution of enrichment scores of target genes between this study and previous study. These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study.
Mentions: We used Wilcoxon Rank Sum test to compare target gene enrichment scores between this study and previous study. A statistically significant difference in the target gene enrichment score distribution was observed (p-value = 1.495e-06). In addition, in order to compare the distribution of enrichment scores of target genes between this study and previous study, we made boxplot and density plot (Figure 5(A,B)). These plots show that the enrichment scores of targets genes in the miRNA modules obtained from this study are statistically significantly higher than those from previous study. In conclusion, we can demonstrate that our pipeline for finding miRNA modules is more efficient than previous method in terms of enrichment of target gene function.

Bottom Line: In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner.On the system level, we identified cooperatively regulating miRNAs in the miRNA association network.We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: MicroRNAs (miRNAs) are key components in post-transcriptional gene regulation in multicellular organisms. As they control cooperatively a large number of their target genes, they affect the complexity of gene regulation. One of the challenges to understand miRNA-mediated regulation is to identify co-regulating miRNAs that simultaneously regulate their target genes in a network perspective.

Results: We created miRNA association network by using miRNAs sharing target genes based on sequence complementarity and co-expression patterns of miRNA-target pairs. The degree of association between miRNAs can be assessed by the level of concordance between targets of miRNAs. Cooperatively regulating miRNAs have been identified by network topology-based approach. Cooperativity of miRNAs is evaluated by their shared transcription factors and functional coherence of target genes. Pathway enrichment analysis of target genes in the cooperatively regulating miRNAs revealed the mutually exclusive functional landscape of miRNA cooperativity. In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner. Sequence and structural similarity analysis within miRNA association network showed that pre-miRNA secondary structure may be involved in the expression of mature miRNA's function.

Conclusions: On the system level, we identified cooperatively regulating miRNAs in the miRNA association network. We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar. This study demonstrates the potential importance of the secondary structures of pre-miRNAs in both cooperativity and specificity of target genes.

Show MeSH