GapMind

GapMind annotates amino acid biosynthesis pathways in bacteria and archaea to identify enzyme candidates, variant pathways, and pathway gaps.

Key Features:

• Pathway coverage: Incorporates numerous variant pathways encompassing 130 different biochemical reactions.
• Database of experimentally-characterized proteins: Relies on a database of experimentally-characterized proteins to reduce error-prone "transitive" annotations.
• Fusion and split protein handling: Detects and correctly handles fusion and split proteins to avoid errors from "best hit" approaches.
• Performance: Analyzes genomic data with a reported runtime of approximately 15 seconds.
• Empirical expansion: Expanded coverage by analyzing genetic data from 35 bacterial species capable of growth in minimal media.
• Discovery of novel genes: Identified previously unrecognized genes for amino acid synthesis, including additional genes for arginine synthesis with succinylated intermediates in Bacteroides thetaiotaomicron.
• Pathway proposals: Proposed that Dyella japonica synthesizes tyrosine from phenylalanine based on genomic analysis.
• "Known" gap classification: Marks steps as "known" gaps when they are missing both in the genome of interest and in a related microbe capable of growth in minimal media.

Scientific Applications:

• Genome annotation: Assigns candidates for enzymes in amino acid biosynthesis pathways in bacteria and archaea.
• Novel gene discovery: Identifies previously unrecognized genes and variant pathway components for amino acid synthesis.
• Gap analysis: Classifies and highlights pathway gaps, including "known" gaps for targeted experimental follow-up.
• Comparative metabolic analysis: Uses genomes from microbes grown in minimal media to compare pathway presence and expand coverage across species.

Methodology:

Relies on a database of experimentally-characterized proteins, handles fusion and split proteins, incorporates variant pathways covering 130 biochemical reactions, analyzes genomic data (reported runtime ≈15 seconds), analyzed genetic data from 35 bacterial species capable of growth in minimal media to expand coverage, and marks gaps as "known" when the same gap is present in a related microbe capable of growth in minimal media.