🧬 AI Gene Review

Overview

The AI Gene Review tool helps researchers and curators review existing Gene Ontology (GO) annotations using strict, defined criteria. It provides a structured workflow for validating annotations using AI-driven analysis combined with literature research and bioinformatics evidence.

Key Features

Quick Start

Installation

1. Install uv for dependency management
2. Clone and install dependencies:

git clone https://github.com/cmungall/ai-gene-review.git
cd ai-gene-review
uv sync --group dev

Basic Usage

Fetch gene data:

uv run ai-gene-review fetch-gene human TP53

Validate a gene review file:

uv run ai-gene-review validate genes/human/TP53/TP53-ai-review.yaml

Generate validation reports with TSV output:

just validate-all  # Creates reports/validation-all.tsv

Fetch publications for a gene:

uv run ai-gene-review fetch-gene-pmids genes/human/TP53/TP53-ai-review.yaml

Generate statistics report:

just stats          # Generate HTML report
just stats-open     # Generate and open in browser

Workflow Overview

Anti-Hallucination Validation

How It Works

Every ontology term requires both an id (semantic identifier) and label (human-readable name):

term:
  id: GO:0005515      # Ontology identifier
  label: protein binding  # Canonical label

Validation Process

The TermValidator performs multi-layer validation:

1. Format Validation: Ensures IDs follow proper CURIE patterns
2. Existence Validation: Verifies terms exist in authoritative ontologies
3. Label Matching: Cross-references provided labels against canonical labels
4. Branch Validation: Ensures GO terms are in correct ontological branches
5. Obsolescence Checking: Flags outdated terms

Why This Prevents Hallucination

• ✅ Dual Verification: Both ID and label must be correct and consistent
• ✅ External Truth Source: Validates against authoritative ontologies
• ✅ Real-time Checking: Uses live API calls to catch fabricated terms
• ✅ Semantic Consistency: Ensures terms make sense in context

Supported Ontologies

The validator supports 10+ major ontologies including GO, HP, MONDO, CL, UBERON, CHEBI, PR, SO, PATO, and NCBITaxon.

Misannotation Analysis

Analysis Framework

Located in analysis/misannotation/ with dedicated tools:

Quick Test Commands:

cd analysis/misannotation

# Quick test with single gene (fast)
just test-quick human TP53

# Full analysis with BLAST (slower)
just analyze-sequence human
just analyze-domains human
just analyze-full human

# Generate summary report
just summarize-risk

Risk Assessment

• HIGH Risk: <25% sequence identity with characterized proteins
• MEDIUM Risk: 25-50% sequence identity
• LOW Risk: >50% sequence identity with consistent domains

Output Formats

• JSON reports: Detailed analysis per gene
• TSV summaries: Easy filtering and analysis
• Risk categorization: HIGH/MEDIUM/LOW classifications

Resources & Links

Gene Review Structure

Each gene review follows a structured YAML format containing:

• Gene metadata: UniProt ID, gene symbol, taxon information
• Description: Comprehensive summary of gene function
• References: Literature and bioinformatics sources
• Existing annotations: Review of current GO annotations with actions
• Core functions: Curated essential gene functions

Example Data

The repository includes example gene reviews for:

• Human: BRCA1, CFAP300, RBFOX3, TP53
• Mouse: Various examples
• Worm: lrx-1

Developer Tools

Available commands using just command runner:

just --list           # Show all available commands
just test             # Run tests, type checking, and linting
just format           # Run code formatting checks
just install          # Install project dependencies
just validate-all     # Validate all genes with TSV output

Case Study: PedH Lanthanide-Dependent Alcohol Dehydrogenase