Analysis

MNDR is not only a knowledge depository but providing a valuable resource for understanding the general features of disease-associated ncRNA network. The rich information on mutual regulations between ncRNAs stored in MNDR provides us a good opportunity to test this conclusion in disease states. Therefore, we have built a simplified disease-associated ncRNAs network based on ncRNAs with the interaction genes. Diverse ncRNAs and interaction genes were represented as nodes and the relationships were denoted as edges. Based on current data, interesting observations have been achieved in visualization and analysis page. As shown in Figure 1, snoRNA htr as hub node have intensively linked to 21 interaction genes in the network. More important, through BCL2, BCL2L1 and BAX, the snoRNA htr can communicate with the lncRNA malat1. Another example is that snoRNA htr and lncRNA h19 are linked by E2F1 and MYC. Since MNDR just integrated lncRNA, piRNA and snoRNA for human, the biggest sub-network only contains 65 nodes and 70 edges, involving 20 lncRNA, 1 snoRNA and 44 interaction genes (Figure 1). Hence, for the more and global analyzing the ncRNA-associated disease network for human, we also integrated human miRNA-associated disease evidences of miRNAs with the target genes in mir2disease database. Inspecting these expanding resources, we found that lncRNA, miRNAs and snoRNA with their interaction/target genes can be integrated into a bigger interlocking ncRNA-associated disease network. As shown in Figure 2, this biggest sub-network have 129 nodes and 149 edges, involving 33 lncRNAs, 1 snoRNA, 19 miRNAs and 76 interaction genes. By integrating human miRNA-associated disease, we found that lncRNA dgcr5, har1a and har1b were connected with hsa-mir-21 via intermediate gene REST. Interestingly, hsa-mir-21 and snoRNA htr were linked by key anti-apoptosis gene BCL2. Similar results were observed that lncRNA dgcr5, har1a and har1b can also communicate with snoRNA htr through alternative route NFKB1-hsa-mir-9-REST (Figure 2). Hence, according to current representations, the two pivot protein coding mRNAs (BCL2 and NFKB1) and several ncRNAs (lncRNA malat1, snoRNA htr and miRNA hsa-mir-21, has-mir-9) collectively play an important role in the ncRNA-associated disease network (Figure 2). Importantly, the crosstalk between lncRNA malat1 and miRNA hsa-mir-21 can be found conserved in mouse ncRNA network. These observations indicated diverse ncRNAs could communicate with each other in disease state through some disease-associated genes in mammalians, highlighting the complexity, conservative and plasticity of the regulatory relationships between diverse ncRNAs and mRNA/proteins in diseases.


Figure 1. The biggest sub-network of ncRNA-associated disease network based on lncRNAs and snoRNAs with the interaction genes in MNDR database. Green, yellow, blue and pink nodes represent lncRNAs, miRNAs, snoRNAs and protein-coding genes respectively.

Figure 2. The biggest sub-network of ncRNA-associated disease network based on lncRNAs, miRNAs and snoRNAs with the interaction genes by integrating mir2disease and MNDR database. Green, yellow, blue and pink nodes represent lncRNAs, miRNAs, snoRNAs and protein-coding genes respectively.