KOBAS

KOBAS annotates gene and protein sets with KEGG Orthology (KO) terms and performs pathway enrichment analysis to identify statistically enriched pathways for interpretation of high-throughput DNA sequencing, microarray, and protein 2D gel data.

Key Features:

• Annotation with KO terms: Maps input nucleotide or amino acid sequences or identifiers to KEGG Orthology (KO) terms linked to KEGG Pathway entries.
• Pathway enrichment analysis: Identifies frequently occurring and statistically enriched pathways by comparing queried sequences against a background distribution.
• Database support: Supports KEGG Pathway, PID, BioCyc, Reactome, Panther, OMIM, KEGG Disease, FunDO, GAD, and NHGRI GWAS for pathway and disease association analyses.
• Sequence similarity search: Uses BLAST sequence similarity searches for annotation when direct identifiers are unavailable.
• ID mapping: Performs direct identifier mapping to genes with known annotations.
• Multiple testing correction: Provides multiple testing correction options for statistical enrichment analyses.
• High-throughput data compatibility: Processes large gene or protein sets derived from DNA sequencing, microarray analysis, and protein 2D gel experiments.
• KO versus GO: Uses KEGG Orthology as an alternative controlled vocabulary to Gene Ontology (GO) with direct linkage to pathways.

Scientific Applications:

• Genome and proteome annotation: Functional annotation of genes and proteins via KO term assignment for downstream pathway analysis.
• Differential expression and enrichment analysis: Identification of statistically enriched pathways among upregulated or differentially expressed gene sets.
• Disease-associated pathway discovery: Linking gene sets to disease databases (OMIM, KEGG Disease, FunDO, GAD, NHGRI GWAS) to identify disease-associated pathways.
• Case study application: Analysis of upregulated genes in Alzheimer's Disease hippocampal CA1 to identify enriched pathways.

Methodology:

Annotation is performed by mapping sequences or identifiers to KEGG Orthology (KO) terms via BLAST or direct ID mapping, linking KO terms to KEGG Pathway and other supported databases, and testing pathway enrichment against a background distribution with statistical tests and multiple testing correction options.