IRBIS

IRBIS identifies conserved complementary regions within unaligned orthologous sequences to detect conserved intra- and intermolecular RNA-RNA interactions.

Key Features:

• "first-fold-then-align" principle: Implements the "first-fold-then-align" principle by searching for complementary sequence conservation prior to alignment.
• Complementary k-mer search: Searches all possible combinations of complementary k-mers for simultaneous conservation before alignment.
• Trimming procedure: Employs a novel trimming procedure to reduce the search space.
• Large-scale analysis: Enables large-scale analyses of both intra- and intermolecular RNA-RNA interactions.
• Cross-species structure prediction: Produces stringent predictions of intramolecular RNA structures across placental mammals, drosophilids, and nematodes.
• Long-range structure detection: Identifies long-range RNA structures implicated in exon skipping, including regions in the mammalian Dystonin gene and the insect Ca-α1D gene.
• Protein-binding site detection: Detects complementary regions that contain Rbfox protein binding sites similar to those in the Enah gene.
• Noncoding RNA interactions: Reveals a high propensity of small nucleolar RNAs (snoRNAs) and long noncoding RNAs (lncRNAs) to base-pair with introns of protein-coding genes, suggesting roles in splicing regulation.
• False discovery insight: Highlights that conserved sequences occurring equally on both DNA strands, such as transcription factor binding sites, can substantially contribute to false discovery rates.

Scientific Applications:

• RNA-RNA interaction discovery: Detect conserved intra- and intermolecular RNA-RNA interactions across unaligned orthologous sequences.
• Comparative RNA structure prediction: Predict conserved intramolecular RNA structures across placental mammals, drosophilids, and nematodes.
• Splicing regulation analysis: Identify long-range RNA structures that may influence exon skipping, exemplified by Dystonin in mammals and Ca-α1D in insects.
• Noncoding RNA–intron interaction studies: Map base-pairing between snoRNAs/lncRNAs and introns of protein-coding genes to investigate potential splicing regulatory roles.
• False discovery assessment: Assess the impact of bidirectional conserved sequences, such as transcription factor binding sites, on false discovery rates in conserved RNA structure searches.

Methodology:

Applies the "first-fold-then-align" principle by searching all combinations of complementary k-mers for simultaneous conservation prior to alignment, uses a novel trimming procedure to reduce the search space, and has been benchmarked on simulated and real datasets.