DIANA-mirPath

DIANA-mirPath performs pathway-level analysis of microRNA (miRNA) regulatory effects by annotating miRNAs and identifying controlled pathways using DIANA-TarBase v7.0 and in silico predictions from DIANA-microT-CDS and TargetScan v6.2 across Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans, Gallus gallus and Danio rerio, focusing on KEGG pathways and Gene Ontology categories.

Key Features:

• Functional Annotation of miRNAs: Applies statistical tests including hypergeometric distributions, unbiased empirical distributions, and meta-analysis statistics to annotate individual or multiple miRNAs.
• Integration of Experimental Data: Incorporates over 600,000 experimentally supported miRNA targets from DIANA-TarBase v7.0 and combines them with in silico predictions from DIANA-microT-CDS and TargetScan v6.2.
• Reverse Search Module: Identifies and visualizes miRNAs that significantly control selected KEGG pathways or GO categories using experimental data and in silico predictions.
• Enrichment Analysis: Performs enrichment analysis by comparing sets of microRNA target genes against KEGG pathways and accounts for combinatorial effects of co-expressed miRNAs.
• Sophisticated Visualizations: Generates dendrograms and heat maps that depict miRNA versus pathway interactions.
• SNP Analysis Module: Detects pathogenic single nucleotide polymorphisms (SNPs) in miRNA target sites.

Scientific Applications:

• Functional interpretation: Maps miRNAs to KEGG pathways and Gene Ontology categories to support functional interpretation of miRNA effects.
• Integrative target prioritization: Combines DIANA-TarBase experimental interactions with DIANA-microT-CDS and TargetScan v6.2 predictions to prioritize miRNA targets.
• Combinatorial regulation analysis: Assesses combinatorial effects of co-expressed miRNAs on pathway modulation using enrichment and meta-analysis statistics.
• Genetic variant impact assessment: Evaluates the impact of pathogenic SNPs in miRNA target sites on regulatory interactions.

Methodology:

Uses hypergeometric distributions, unbiased empirical distributions and meta-analysis statistics; integrates DIANA-TarBase v7.0 with DIANA-microT-CDS and TargetScan v6.2; performs enrichment analysis against KEGG pathways; employs a reverse search to find miRNAs controlling selected pathways or GO categories; generates dendrograms and heat maps; identifies pathogenic SNPs in miRNA target sites.