# Genomic Consultant

A practical genomics analysis toolkit for Trio WES (Whole Exome Sequencing) data analysis, including ClinVar/ACMG annotation, GWAS trait analysis, and pharmacogenomics.

## Analysis Scripts

### 1. Trio Analysis (`trio_analysis.py`)
Comprehensive trio-based variant analysis with de novo detection, compound heterozygosity, and inheritance pattern annotation.

```bash
python trio_analysis.py <vcf_path> <output_dir>
```

### 2. ClinVar/ACMG Annotation (`clinvar_acmg_annotate.py`)
Annotates variants with ClinVar clinical significance and generates ACMG-style evidence tags.

```bash
python clinvar_acmg_annotate.py <vcf_path> <output_path> [sample_idx]
```

### 3. GWAS Comprehensive Analysis (`gwas_comprehensive.py`)
Comprehensive GWAS trait analysis with 201 curated SNPs across 18 categories:
- Gout / Uric acid metabolism
- Kidney disease
- Hearing loss
- Autoimmune diseases
- Cancer risk
- Blood clotting / Thrombosis
- Thyroid disorders
- Bone health / Osteoporosis
- Liver disease (NAFLD)
- Migraine
- Longevity / Aging
- Sleep
- Skin conditions
- Cardiovascular disease
- Metabolic disorders
- Eye conditions
- Neuropsychiatric
- Other traits

```bash
python gwas_comprehensive.py <vcf_path> <output_path> [sample_idx]
```

### 4. PharmGKB Full Analysis (`pharmgkb_full_analysis.py`)
Comprehensive pharmacogenomics analysis using the PharmGKB clinical annotations database.

```bash
python pharmgkb_full_analysis.py <vcf_path> <output_path> [sample_idx]
```

### 5. GWAS Trait Lookup (`gwas_trait_lookup.py`)
Original curated GWAS trait lookup (smaller SNP set).

```bash
python gwas_trait_lookup.py <vcf_path> <output_path> [sample_idx]
```

### 6. Basic Pharmacogenomics (`pharmacogenomics.py`)
Basic pharmacogenomics analysis with common drug-gene interactions.

## Prerequisites

- Python 3.8+
- conda environment with bioinformatics tools:
  ```bash
  conda create -n genomics python=3.10
  conda activate genomics
  conda install -c bioconda bcftools snpeff gatk4
  ```

## Reference Databases Required

- **ClinVar**: VCF from NCBI
- **PharmGKB**: Clinical annotations TSV
- **dbSNP**: For rsID annotation
- **GRCh37/hg19 reference genome**

## Data Directory Structure

```
/Volumes/NV2/
├── genomics_analysis/
│   └── vcf/
│       ├── trio_joint.vcf.gz          # Joint-called VCF
│       ├── trio_joint.rsid.vcf.gz     # With rsID annotations
│       └── trio_joint.snpeff.vcf      # With SnpEff annotations
└── genomics_reference/
    ├── clinvar/
    ├── pharmgkb/
    ├── dbsnp/
    └── gwas_catalog/
```

## Sample Index Mapping

For trio VCF files:
- Index 0: Mother
- Index 1: Father
- Index 2: Proband

## Output Reports

Each script generates detailed reports including:
- Summary statistics
- Risk variant identification
- Family comparison (for trio data)
- Clinical annotations and recommendations

## License

Private use only.