An Integrative Analysis of ncRNA-mRNA Using Co-expression Network to Discover Potential Contributions of Coding-non-coding RNA Clusters

Non-coding RNAs (ncRNAs), especially for microRNAs (miRNAs), have been widely s tudied as crucial negative regulatory molecules. Long noncoding RNAs (lncRNAs) also have attracted the attention of researchers due to their potential contribution in multiple essential biological processes. To understand th e p otential in teractions between miRNAs, l ncRNAs and mRNAs a nd their p otential r oles i n tumorigenesis, w e reported an i ntegrative an alysis t o predict clustered ncRNA-mRNA with consistent functions, and predict clusters at the single molecule level. The method aims to discover those potential clusters o f coding-non-coding RNAs that maybe contribute to occurrence and d evelopment of human diseases. Based on e xpression profiles and abnormal expression profiles of m iRNAs, l ncRNAs and m RNAs, co -expression network analysis can be performed at the single molecule and multiple RNA molecules, respectively. Some cl ustered R NAs at t he s ingle R NA m olecule can be obtained, an d t hese m embers al ways h ave co nsistent f unctions. Although t hese non-coding RNAs or coding RNAs ar e an alyzed at t he s ingle molecule l evel, they have close functional relationships, especially between miRNAs and their target mRNAs. Therefore, based on their potential functional and sequence relationships, further coding-non-coding co-expression network can be constructed based on integrative expression and functional analysis acr oss d ifferent molecule levels. The comparison analysis of the single and multiple molecules will provide m ore i nformation t o pr edict i nteraction between miRNAs a nd lncRNAs, ncRNAs and mRNAs. Furthermore, based on special miRNA group 1 This w ork was s upported by t he N ational N atural Science F oundation of C hina ( No. 61301251, 81072389 and 81373102), the Research Fund for the Doctoral Program of Higher Education of China (No. 211323411002 and 20133234120009), the China Postdoctoral Science Foundation funded project (No. 2012M521100), the key Grant of the Natural Science Foundation of the J iangsu Higher Education Institutions of China (No. 10KJA33034), t he National N atural S cience F oundation of J iangsu ( No. B K20130885), t he N atural Science Foundation of t he J iangsu H igher E ducation I nstitutions ( No. 1 2KJB310003 a nd 13KJB330003), t he J iangsu Planned Projects f or Postdoctoral R esearch F unds ( No. 1201022B), the Science and Technology Development Fund Key Project of Nanjing Medical University (No. 2012NJMU001), and the Priority Academic Program D evelopment of Jiangsu Higher Education Institutions (PAPD). Proceedings IWBBIO 2014. Granada 7-9 April, 2014 1568 with potential functional relationships, such as miRNA gene c luster and gene family, especially for complex miRNA processing and maturation mechanism, and p otential miRNA-miRNA in teraction, m iRNAs are i nvolved i n t he m ore complex regulatory network and pattern. The location distributions and potential s equence correlations ar e al so an alyzed acr oss d ifferent R NA molecules, which maybe implicate the potential functional relationships between ncRNAs and m RNAs, es pecially b etween m iRNAs an d lncRNAs. T he s ystematic an d large-scale co-expression networks based on the single and multiple RNA molecule l evels will provide m ore association of c oding-non-coding R NAs a nd their potential contributions in occurrence and development of diseases. Finally, the analysis also implicates the functional and evolutionary relationships across coding and non-coding RNAs.