title: Discovery of microRNA regulatory networks by integrating multidimensional high-throughput data.
abstract: MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) of approximately 22 nt that regulate the expression of a large fraction of genes by targeting messenger RNAs (mRNAs). However, determining the biologically significant targets of miRNAs is an ongoing challenge. In this chapter, we describe how to identify miRNA-target interactions and miRNA regulatory networks from high-throughput deep sequencing, CLIP-Seq (HITS-CLIP, PAR-CLIP) and degradome sequencing data using starBase platforms. In starBase, several web-based and stand-alone computational tools were developed to discover Argonaute (Ago) binding and cleavage sites, miRNA-target interactions, perform enrichment analysis of miRNA target genes in Gene Ontology (GO) categories and biological pathways, and identify combinatorial effects between Ago and other RNA-binding proteins (RBPs). Investigating target pathways of miRNAs in human CLIP-Seq data, we found that many cancer-associated miRNAs modulate cancer pathways. Performing an enrichment analysis of genes targeted by highly expressed miRNAs in the mouse brain showed that many miRNAs are involved in cancer-associated MAPK signaling and glioma pathways, as well as neuron-associated neurotrophin signaling and axon guidance pathways. Moreover, thousands of combinatorial binding sites between Ago and RBPs were identified from CLIP-Seq data suggesting RBPs and miRNAs coordinately regulate mRNA transcripts. As a means of comprehensively integrating CLIP-Seq and Degradome-Seq data, the starBase platform is expected to identify clinically relevant miRNA-target regulatory relationships, and reveal multi-dimensional post-transcriptional regulatory networks involving miRNAs and RBPs. starBase is available at                  http://starbase.sysu.edu.cn/                                .
authors: Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Jian-Hua
authors: JH
authors: Yang
authors: Liang-Hu
authors: LH
authors: Qu
mesh_terms: D000818:Animals; D001483:Base Sequence; D030561:Databases, Nucleic Acid; D053263:Gene Regulatory Networks / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D020871:RNA Stability / Q000235:genetics
chemical_list: D035683:MicroRNAs