isomiR-SEA

isomiR-SEA performs seed-aware alignments to identify and quantify microRNAs (miRNAs) and their isomiR variants and to detect miRNA:mRNA interaction sites from RNA-Seq data.

Key Features:

• Specialized alignment algorithm: Employs a multi-phase, seed-aware alignment algorithm tailored to miRNA structure, including explicit consideration of the seed region.
• Accurate isomiR detection: Evaluates mismatches during alignment phases to distinguish and classify isomiR variants from canonical miRNA sequences.
• miRNA:mRNA interaction awareness: Considers miRNA:mRNA interaction sites and structural nuances of miRNAs during alignment to identify conserved interaction sites.
• Integration of biological evidence: Incorporates biological evidence about miRNA structure to map tags to known miRNA sequences and improve assignment accuracy.
• No post-alignment filtering required: Integrates isomiR and interaction-site evaluations during initial alignment phases to avoid additional post-alignment filtering steps.
• Performance validation: Validated on two public RNA-Seq datasets with reported superior accuracy in miRNA expression level assessment compared to existing tools.

Scientific Applications:

• miRNA expression profiling: Provides accurate quantification of miRNA expression levels from RNA-Seq data, including isomiR-specific counts.
• Transcriptome analysis: Supports analysis of regulatory networks by delivering variant classifications and interaction-site information for incorporation into transcriptome studies.
• Functional genomics: Enables investigation of gene regulation mechanisms mediated by miRNAs through precise identification of conserved miRNA:mRNA interaction sites and isomiR variants.

Methodology:

Uses a multi-phase alignment process that prioritizes detection of miRNA seed regions, evaluates mismatches to differentiate isomiRs, integrates miRNA structural evidence into alignment scoring, and performs interaction-site identification during initial alignment to avoid post-alignment filtering.