CASSIS

CASSIS predicts secondary metabolite (SM) gene clusters in eukaryotic genomes by detecting promoter-region regulatory motif enrichment around biosynthetic anchor genes to delineate co-localized co-regulated cluster boundaries.

Key Features:

• SM gene cluster prediction: Predicts secondary metabolite gene clusters in eukaryotic genomes by locating motif-enriched regions around anchor genes.
• Anchor gene detection (SMIPS): Uses Secondary Metabolites by InterProScan (SMIPS) for genome-wide detection of anchor genes.
• Anchor enzyme targeting: Targets anchor enzymes including polyketide synthases, non-ribosomal peptide synthetases, and dimethylallyl tryptophan synthases.
• Regulatory motif "islands": Identifies "islands" of enriched regulatory motifs in promoter regions to define cluster boundaries.
• Motif-based approach: Relies on regulatory motif enrichment instead of protein similarity to predict clusters.
• Validation: Validated with cross-validation experiments reporting high sensitivity and specificity for SM cluster identification.

Scientific Applications:

• SM biosynthetic cluster discovery: Identification of biosynthetic gene clusters responsible for secondary metabolites in eukaryotic genomes.
• Regulatory network analysis: Studying co-regulation and promoter architecture of biosynthetic genes within clusters.
• Natural product prioritization: Prioritizing candidate SM clusters for natural product discovery and pharmaceutical lead identification.
• Method benchmarking: Comparing motif-based cluster prediction to protein-similarity-based methods.

Methodology:

Leverages the concept of gene co-regulation; uses SMIPS for genome-wide anchor gene detection; searches promoter regions for enriched motifs to identify "islands" around anchor genes and delineate clusters; validated by cross-validation experiments assessing sensitivity and specificity.