Figure 1.
Evaluation of the conserved co-expression relationships.
(A) Pie charts of miRNA expression data from human (top) and mouse (bottom) included in the analysis. Colors represent different tissues. (B) Probability density of the number of co-expression links identified through the permutation of orthologous miRNAs. The permutation experiment was repeated 100 times. (C) ROC curves used to quantify the significant of these relationships using a PCR-based miRNA expression data (GSE23024).
Figure 2.
Functional relationships of 182 conserved co-expressed miRNA pairs.
(A) Genomic distances of the observed miRNA pairs, which are significantly shorter than the distances of non co-expressed miRNA pairs (Wilcoxon rank sum test, p-value<2.2e-16). (B) Probability density of the number of miRNA pairs that belong to the same cluster from randomly selected miRNA pairs. The count observed in the real co-expressed miRNA pairs (50, located by the blue arrow) is significantly higher than those in the random pairs (p-value<0.001). (C) Probability density of the number of miRNA pairs that share common TFs from randomly selected miRNA pairs. The count observed in the real co-expressed miRNA pairs (47, located by the blue arrow) is significantly higher than those in the random pairs (p-value<0.001). (D) Probability density of the number of miRNA pairs belonging to the same family from randomly selected miRNA pairs. The count observed in the real co-expressed miRNA pairs (44, located by the blue arrow) is significantly higher than those in the random pairs (p-value<0.001). (E) The number of miRNA pairs with significantly overlapping targets in the real conserved co-expression pairs (132, located by the blue arrow) is significantly higher than those in the randomly selected miRNA pairs (p-value = 0.001). (F) The number of miRNA pairs with common targets significantly involved in at least one biological process in the real conserved co-expression pairs (88, located by the blue arrow) is significantly higher than those in the randomly selected miRNA pairs (p-value = 0.022). (G) The number of miRNA pairs with significantly overlapping expression-related genes in the real conserved co-expression pairs (81, located by the blue arrow) is significantly higher than those in the randomly selected miRNA pairs (p-value = 0.034).
Figure 3.
Dysfunction of multiple co-expressed microRNAs in a common disease.
(A) The distribution of the number of miRNA pairs sharing a common disease from random selections of miRNA pairs. The number observed in the real conserved co-expression pairs (located by the blue arrow) is significantly higher than those in the randomly selected miRNA pairs (p-value<0.001). (B) The distribution of the number of miRNA pairs sharing a common disease from random selections of disease miRNAs. The number observed in the real conserved co-expression pairs (located by the blue arrow) is significantly higher than those from the randomly selected disease miRNAs (p-value<0.001). (C) The numbers of miRNAs associated with different human diseases in each sub-network.
Figure 4.
The human conserved miRNA co-expression network.
Known disease miRNAs (green) were mapped onto the network. Three disease-related miRNA sub-networks in the dashed boxes were identified. MiRNAs with knockout/transfection experiments are labeled with red stars. Biological processes significantly overrepresented in common targets of each sub-network are recorded on top of the corresponding dashed box with black color. Using miRNAs with knockout/transfection experiments in each sub-network, biological processes significantly overrepresented in consistently affected genes are recorded at the bottom of the corresponding dashed box with blue color.