Detecting TF-miRNA-gene network based modules for 5hmC and 5mC brain samples: a intra- and inter-species case-study...

Study of epigenetics is currently a high-impact research topic. Multi stage methylation is also an area of high-dimensional prospect. In this article, we provide a new study (intra and inter-species study) on brain tissue between human and rhesus on two methylation cytosine variants based data-profiles (viz., 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) samples) through TF-miRNA-gene network based module detection.

First of all, we determine differentially 5hmC methylated genes for human as well as rhesus for intra-species analysis, and differentially multi-stage methylated genes for inter-species analysis. Thereafter, we utilize weighted topological overlap matrix (TOM) measure and average linkage clustering consecutively on these genesets for intra- and inter-species study.We identify co-methylated and multi-stage co-methylated gene modules by using dynamic tree cut, for intra-and inter-species cases, respectively. Each module is represented by individual color in the dendrogram. Gene Ontology and KEGG pathway based analysis are then performed to identify biological functionalities of the identified modules. Finally, top ten regulator TFs and targeter miRNAs that are associated with the maximum number of gene modules, are determined for both intra-and inter-species analysis.

The novel TFs and miRNAs obtained from the analysis are: MYST3 and ZNF771 as TFs (for human intra-species analysis), BAZ2B, RCOR3 and ATF1 as TFs (for rhesus intra-species analysis), and mml-miR-768-3p and mml-miR-561 as miRs (for rhesus intra-species analysis); and MYST3 and ZNF771 as miRs(for inter-species study). Furthermore, the genes/TFs/miRNAs that are already found to be liable for several brain-related dreadful diseases as well as rare neglected diseases (e.g., wolf Hirschhorn syndrome, Joubarts Syndrome, Huntington's disease, Simian Immunodeficiency Virus(SIV) mediated enchaphilits, Parkinsons Disease, Bipolar disorder and Schizophenia etc.) are mentioned.