microRNA Target Prediction Algorithms
microCLIP
microCLIP (http://www.microrna.gr/microCLIP) algorithm can be used for the transcriptome-wide identification of miRNA-target interactions. It operates on AGO-PAR-CLIP sequencing reads, requiring a SAM/BAM alignment file and a list of miRNAs as minimum input. microCLIP framework combines deep learning classifiers under a super learning scheme for CLIP-guided detection of miRNA interactions. The model incorporates a series of significant breakthroughs in PAR-CLIP analysis, revolutionizing the experiment’s scope and robustness
DIANA-microT-CDS
DIANA-microT-CDS (http://www.microrna.gr/microT-CDS) is the 5th version of the microT algorithm. It is specifically trained on a positive and a negative set of miRNA Recognition Elements (MREs) located in both the 3′-UTR and CDS regions. DIANA-microT-CDS delivers a significant increase in sensitivity relative to the previous version (65% vs. 52%), evaluated using experimental proteomics data. It exhibited the highest sensitivity at any level of specificity, when compared against other state-of-the-art implementations.
For a significantly updated set of interactions using this algorithm, please see our web-server: DIANA-microT 2023 (www.microrna.gr/microt_webserver/)
Databases of experimentally supported microRNA (non-)coding targets
TarBase v9.0
TarBase v9.0 (https://microrna.gr/tarbase) is a reference database devoted to the indexing of experimentally supported microRNA (miRNA) targets. DIANA-TarBase is coming of age, with more than a decade of continuous support in the non-coding RNA field. It catalogues ∼6 million entries, comprising ∼2 million unique miRNA–gene pairs, supported by 37 experimental (high- and low-yield) protocols in 172 tissues and cell-types.
LncBase v3.0
LncBase v3.0 (http://www.microrna.gr/LncBasev3/) presents an extensive collection of miRNA:lncRNA interactions. More than 70,000 low and high-throughput, (in)direct miRNA:lncRNA experimentally supported interactions, derived from manually curated publications and the analysis of 153 AGO CLIP-Seq libraries are indexed. LncBase v3 also hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm.
Characterization of microRNA Promoters and their Regulators
microTSS
How to detect the elusive microRNA genes
microTSS (http://www.microrna.gr/microTSS/) microTSS is a machine-learning algorithm that provides highly accurate, single-nucleotide resolution predictions for intergenic miRNA transcription start sites (TSSs). microTSS integrates high-resolution RNA-Seq data with active transcription marks derived from chromatin immunoprecipitation and DNase-Seq to enable the characterization of tissue-specific promoters. microTSS is readily applicable to any cell or tissue samples and constitutes the missing part towards integrating the regulation of miRNA transcription into the modelling of tissue-specific regulatory networks.
miRGen v4.0
Elucidating the combinatorial effect of miRNAs on molecular pathways
miRGen v4.0 (http://www.microrna.gr/mirgenv4) provides accurate cell-line-specific miRNA gene Transcription Start Sites (TSSs), coupled with genome-wide maps of Transcription Factor Binding Sites (TFBSs). More than 7.3 billion RNA-, ChIP- and DNase-Seq next generation sequencing reads were analyzed/assembled and combined with state-of-the-art miRNA TSS prediction and TFBS identification algorithms.
Incorporating microRNAs in Pathways
miRPath v4.0
Elucidating the combinatorial effect of miRNAs on molecular pathways
miRPath v4.0 (http://www.microrna.gr/miRPathv4) is an online software suite dedicated to the assessment of miRNA regulatory roles and the identification of controlled pathways.
The miRPath web server renders possible the functional annotation of one or more miRNAs using standard (hypergeometric distributions), unbiased empirical distributions and/or meta-analysis statistics. Gene Ontology and KEGG Pathway terms are currently supported in 7 species. In its latest version it introduces the capacity to tailor its target-based miRNA functional analysis engine to specific biological and/or experimental contexts.
Uncovering microRNAs and Transcription Factors with Crucial Roles in NGS Expression Data
mirExTra v2.0
mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined Differential Expression Analysis (DEA) of mRNAs and miRNAs to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets, enabling users to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression.
microRNAs as circulating biomarkers
plasmiR is an exclusively manually curated database of circulating miRNA biomarkers. It collects and caters experimental evidence on the biomarker potential of more than 250 blood, plasma or serum miRNAs against 112 diseases. plasmiR features more than 790 diagnostic entries and more than 220 prognostic entries which are annotated with their respective outcomes. Extensive effort was placed to not include potentially spurious results from articles merely assessing differential abundance; instead plasmiR features evidence for potential biomarkers that was specifically assessed via adequate statistical methods (e.g. Receiver Operating Characteristic curve analysis to test diagnostic value and Cox-regression analysis to test prognostic value).
Web Servers
DIANA-microT 2023
DIANA-microT 2023 (www.microrna.gr/microt_webserver/), brings forward a significantly updated set of interactions using the DIANA-microT-CDS algorithm which has been executed utilizing annotation information from Ensembl v102, miRBase 22.1 and, for the first time, MirGeneDB 2.1, yielding more than 83 million interactions in human, mouse, rat, chicken, fly and worm species. Additionally, this version delivers predicted interactions of miRNAs encoded from 20 viruses against host transcripts from human, mouse and chicken species.
DIANA-web server 5.0
DIANA web server v5.0 has innate support to the Ensembl (v.69), miRBase (miRBase 18) version and nomenclature, while keeping backwards compatibility with all previous miRBase versions for selected tools, such as DIANA-TarBase. All available tools have been extended to support by default Drosophila melanogaster and Caenorhabditis elegans (as well as Homo sapiens and Mus musculus). DIANA web server also supports a series of sophisticated workflows enabling users without the necessary bioinformatics infrastructure to perform advanced multi-step functional miRNA analyses. All available tools and databases are now accessible programmatically by a REST web service interface. DIANA-Web Server v5.0 provides extensive support for Biological Workflow Management Applications such as Taverna. Specifically, a DIANA-labs Plug-in has been developed, which embeds into the Taverna arsenal all the available tools and services. Furthermore, DIANA services and example workflows are available in major relevant websites such as BioCatalogue and myExperiment.