DIANA-LncBase

Overview

DIANA-LncBase is a reference repository cataloging experimentally supported miRNA-lncRNA interactions. The database serves researchers investigating the complex interplay between microRNAs and long non-coding RNAs, which plays crucial roles in post-transcriptional gene regulation, competing endogenous RNA (ceRNA) networks, and various physiological and pathological processes.

Database Content

Interaction Data (v3.0)

• ~500,000 total entries
• ~240,000 unique miRNA-lncRNA pairs (tissue and cell type specific)
• Species: Human and mouse
• 1,551 miRNAs targeting lncRNAs
• 24,618 targeted lncRNAs
• 192 cell types and 51 tissues
• 162 experimental conditions

Experimental Support

• 14 experimental methodologies:
  • Low-yield: Reporter genes, northern blot, qPCR, RIP-qPCR, biotin miRNA tagging (242 interactions)
  • High-throughput: ~239,000 interactions from:
    • AGO-CLIP-Seq: 236 libraries analyzed with microCLIP algorithm (~370,000 binding events)
    • CLEAR-CLIP & chimeric fragments: 2,924 miRNA-lncRNA chimeras
    • Microarray perturbation: 86 experiments analyzed (2,155 interactions)

Data Sources

• Manual curation: 159 publications with 730+ interactions
• High-throughput analysis: >300 datasets from GEO, ENCODE, DDBJ
• 236 AGO-CLIP-Seq libraries (88 PAR-CLIP, 148 HITS-CLIP) analyzed with microCLIP framework

Key Features

lncRNA Sequences

• 53,250 lncRNA transcripts: GENCODE v30, RefSeq 109-106, Cabili et al.
• 27,009 pseudogene transcripts
• Categories: sense, antisense, lincRNAs, processed transcripts, bidirectional promoter lncRNAs, 3’ overlapping ncRNAs, macro lncRNA

Expression Profiles

• 103 RNA-Seq libraries analyzed (~19.3 billion reads)
• 48 whole transcriptome datasets (22 cell types/tissues)
• 55 subcellular localization datasets (15 cell types/tissues)
• Nucleus vs. cytoplasm expression with Relative Concentration Index (RCI)
• TPM (Transcripts Per Million) values for abundance quantification

Variant Annotation

• 67,966 MREs with known short variant information
• 9,940 lncRNA transcripts with variant-related MREs
• 34,438 unique variants from:
  • dbSNP (48.6% of variant-MRE pairs)
  • COSMIC (47.5% - somatic mutations)
  • ClinVar (3.9% - clinical variants)

Advanced Analysis

• microCLIP algorithm: CLIP-Seq-guided framework using 131 descriptors including:
  • AGO-CLIP features (substitution ratios, coverage metrics)
  • Binding characteristics (binding type, flanking AU content)
  • Energy-related metrics and sequence-based characteristics
• ~90,000 intronic miRNA binding events appropriately labeled
• 2,220 viral miRNA binding events (EBV, KSHV) on host lncRNAs

Database Interface

Query Capabilities

• Search by miRNA/gene names or identifiers (ENSEMBL, miRBase, RefSeq, Cabili)
• Genomic location search for MREs on lncRNA transcripts
• Filtering by:
  • Species, cell types, tissues
  • Experimental methodologies
  • Transcript biotype
  • miRNA confidence level (from miRBase)
  • Short variant information

Interactive Visualizations

• Correlation plots: Explore clustering of miRNA-lncRNA interactions across cell types/tissues (Pearson’s r coefficient)
• Expression bar plots: View lncRNA abundance in different cell types and subcellular compartments
• UCSC Genome Browser integration: Visualize miRNA binding events and MRE-overlapping variant locations

Inter-connections

• RNAcentral: Integrated since 2015, interactions viewable per miRNA
• DIANA-TarBase: ~1 million experimentally supported miRNA-mRNA pairs
• DIANA-microT-CDS: In silico predicted miRNA targets
• DIANA-miRPath: miRNA functional analysis

Methodological Advances (v3.0 vs. v2.0)

• 2-fold increase in high-throughput datasets (322 vs. 153)
• First database using microCLIP CLIP-Seq-guided algorithm for AGO-CLIP-Seq analysis
• subcellular localization data in nucleus/cytoplasm
• Short variant annotation on miRNA target sites
• Enhanced interface with advanced filtering and interactive visualizations

Research Applications

• Study of miRNA-lncRNA regulatory networks
• Investigation of lncRNA sponge functions in ceRNA networks
• Analysis of tissue and cell type specific interactions
• Understanding subcellular localization effects on lncRNA function
• Variant analysis on miRNA-lncRNA binding sites

Website Updates

The database was completely redesigned using Angular v.8 frontend, Java Spring/.NET Core 2.2 backend, and PostgreSQL with optimized indices for fast query execution.

Funding

Supported by ELIXIR-GR Infrastructure [MIS-5002780], co-financed by Greece and the European Union (European Regional Development Fund).

Citation

Karagkouni D, Paraskevopoulou MD, Tastsoglou S, et al. DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts. Nucleic Acids Research. 2020;48(D1):D101-D110. doi:10.1093/nar/gkz1036