Gtars: Genomic Tools and Algorithms in Rust

# Gtars: Genomic Tools and Algorithms in Rust

## Overview

Gtars is a high-performance Rust toolkit for manipulating, analyzing, and processing genomic interval data. It provides specialized tools for overlap detection, coverage analysis, tokenization for machine learning, and reference sequence management.

Use this skill when working with:
- Genomic interval files (BED format)
- Overlap detection between genomic regions
- Coverage track generation (WIG, BigWig)
- Genomic ML preprocessing and tokenization
- Fragment analysis in single-cell genomics
- Reference sequence retrieval and validation

## Installation

### Python Installation

Install gtars Python bindings:

```bash
uv pip install gtars
```

### CLI Installation

Install command-line tools (requires Rust/Cargo):

```bash
# Install with all features
cargo install gtars-cli --features "uniwig overlaprs igd bbcache scoring fragsplit"

# Or install specific features only
cargo install gtars-cli --features "uniwig overlaprs"
```

### Rust Library

Add to Cargo.toml for Rust projects:

```toml
[dependencies]
gtars = { version = "0.1", features = ["tokenizers", "overlaprs"] }
```

## Core Capabilities

Gtars is organized into specialized modules, each focused on specific genomic analysis tasks:

### 1. Overlap Detection and IGD Indexing

Efficiently detect overlaps between genomic intervals using the Integrated Genome Database (IGD) data structure.

**When to use:**
- Finding overlapping regulatory elements
- Variant annotation
- Comparing ChIP-seq peaks
- Identifying shared genomic features

**Quick example:**
```python
import gtars

# Build IGD index and query overlaps
igd = gtars.igd.build_index("regions.bed")
overlaps = igd.query("chr1", 1000, 2000)
```

See `references/overlap.md` for comprehensive overlap detection documentation.

### 2. Coverage Track Generation

Generate coverage tracks from sequencing data with the uniwig module.

**When to use:**
- ATAC-seq accessibility profiles
- ChIP-seq coverage visualization
- RNA-seq read coverage
- Differential coverage analysis

**Quick example:**
```bash
# Generate BigWig coverage track
gtars uniwig generate --input fragments.bed --output coverage.bw --format bigwig
```

See `references/coverage.md` for detailed coverage analysis workflows.

### 3. Genomic Tokenization

Convert genomic regions into discrete tokens for machine learning applications, particularly for deep learning models on genomic data.

**When to use:**
- Preprocessing for genomic ML models
- Integration with geniml library
- Creating position encodings
- Training transformer models on genomic sequences

**Quick example:**
```python
from gtars.tokenizers import TreeTokenizer

tokenizer = TreeTokenizer.from_bed_file("training_regions.bed")
token = tokenizer.tokenize("chr1", 1000, 2000)
```

See `references/tokenizers.md` for tokenization documentation.

### 4. Reference Sequence Management

Handle reference genome sequences and compute digests following the GA4GH refget protocol.

**When to use:**
- Validating reference genome integrity
- Extracting specific genomic sequences
- Computing sequence digests
- Cross-reference comparisons

**Quick example:**
```python
# Load reference and extract sequences
store = gtars.RefgetStore.from_fasta("hg38.fa")
sequence = store.get_subsequence("chr1", 1000, 2000)
```

See `references/refget.md` for reference sequence operations.

### 5. Fragment Processing

Split and analyze fragment files, particularly useful for single-cell genomics data.

**When to use:**
- Processing single-cell ATAC-seq data
- Splitting fragments by cell barcodes
- Cluster-based fragment analysis
- Fragment quality control

**Quick example:**
```bash
# Split fragments by clusters
gtars fragsplit cluster-split --input fragments.tsv --clusters clusters.txt --output-dir ./by_cluster/
```

See `references/cli.md` for fragment processing commands.

### 6. Fragment Scoring

Score fragment overlaps against reference datasets.

**When to use:**
- Evaluating fragment enrichment
- Comparing experimental data to references
- Quality metrics computation
- Batch scoring across samples

**Quick example:**
```bash
# Score fragments against reference
gtars scoring score --fragments fragments.bed --reference reference.bed --output scores.txt
```

## Common Workflows

### Workflow 1: Peak Overlap Analysis

Identify overlapping genomic features:

```python
import gtars

# Load two region sets
peaks = gtars.RegionSet.from_bed("chip_peaks.bed")
promoters = gtars.RegionSet.from_bed("promoters.bed")

# Find overlaps
overlapping_peaks = peaks.filter_overlapping(promoters)

# Export results
overlapping_peaks.to_bed("peaks_in_promoters.bed")
```

### Workflow 2: Coverage Track Pipeline

Generate coverage tracks for visualization:

```bash
# Step 1: Generate coverage
gtars uniwig generate --input atac_fragments.bed --output coverage.wig --resolution 10

# Step 2: Convert to BigWig for genome browsers
gtars uniwig generate --input atac_fragments.bed --output coverage.bw --format bigwig
```

### Workflow 3: ML Preprocessing

Prepare genomic data for machine learning:

```python
from gtars.tokenizers import TreeTokenizer
import gtars

# Step 1: Load training regions
regions = gtars.RegionSet.from_bed("training_peaks.bed")

# Step 2: Create tokenizer
tokenizer = TreeTokenizer.from_bed_file("training_peaks.bed")

# Step 3: Tokenize regions
tokens = [tokenizer.tokenize(r.chromosome, r.start, r.end) for r in regions]

# Step 4: Use tokens in ML pipeline
# (integrate with geniml or custom models)
```

## Python vs CLI Usage

**Use Python API when:**
- Integrating with analysis pipelines
- Need programmatic control
- Working with NumPy/Pandas
- Building custom workflows

**Use CLI when:**
- Quick one-off analyses
- Shell scripting
- Batch processing files
- Prototyping workflows

## Reference Documentation

Comprehensive module documentation:

- **`references/python-api.md`** - Complete Python API reference with RegionSet operations, NumPy integration, and data export
- **`references/overlap.md`** - IGD indexing, overlap detection, and set operations
- **`references/coverage.md`** - Coverage track generation with uniwig
- **`references/tokenizers.md`** - Genomic tokenization for ML applications
- **`references/refget.md`** - Reference sequence management and digests
- **`references/cli.md`** - Command-line interface complete reference

## Integration with geniml

Gtars serves as the foundation for the geniml Python package, providing core genomic interval operations for machine learning workflows. When working on geniml-related tasks, use gtars for data preprocessing and tokenization.

## Performance Characteristics

- **Native Rust performance**: Fast execution with low memory overhead
- **Parallel processing**: Multi-threaded operations for large datasets
- **Memory efficiency**: Streaming and memory-mapped file support
- **Zero-copy operations**: NumPy integration with minimal data copying

## Data Formats

Gtars works with standard genomic formats:

- **BED**: Genomic intervals (3-column or extended)
- **WIG/BigWig**: Coverage tracks
- **FASTA**: Reference sequences
- **Fragment TSV**: Single-cell fragment files with barcodes

## Error Handling and Debugging

Enable verbose logging for troubleshooting:

```python
import gtars

# Enable debug logging
gtars.set_log_level("DEBUG")
```

```bash
# CLI verbose mode
gtars --verbose <command>
```