Gtars: Genomic Tools and Algorithms in Rust

Overview

Gtars (from databio, the lab behind geniml) is a high-performance Rust toolkit for manipulating, analyzing, and processing genomic interval data. Its primary purpose is to be the performance-critical backend for geniml, a Python library for machine learning on genomic intervals. It provides overlap/set operations, IGD overlap indexing, coverage (uniwig) tracks, region tokenization for ML, single-cell fragment pseudobulking, and GA4GH refget sequence-collection management.

Use this skill when working with:

• Genomic interval files (BED) — overlaps, jaccard, set ops, coverage
• IGD indexing for fast overlap queries over large interval databases
• Coverage / accumulation tracks via uniwig
• Genomic ML preprocessing and region tokenization
• Single-cell fragment files (split into pseudobulks by cluster)
• Reference sequence digests and retrieval (refget)

Version note: examples are verified against the `gtars` Python package v0.8 (PyPI). The Python API is exposed through submodules — gtars.models, gtars.tokenizers, gtars.refget, gtars.utils — NOT as flat top-level functions. There is no gtars.igd or gtars.uniwig Python submodule; IGD building and uniwig track generation are CLI-only.

Installation

Python package

uv pip install gtars   # or: uv add gtars

Import surface (verified, v0.8):

from gtars.models import RegionSet, Region, RegionSetList
from gtars.tokenizers import Tokenizer, tokenize_fragment_file
from gtars import refget          # RefgetStore, digest_fasta, sha512t24u_digest, ...
from gtars import utils           # read/write .gtok token files

CLI (separate Rust binary)

The CLI ships as the gtars-cli crate (binary name gtars) and is installed with Cargo. Most subcommands are behind feature flags:

# All commonly used commands
cargo install gtars-cli --features "uniwig overlaprs igd bbcache scoring fragsplit genomicdist"

# Or a subset
cargo install gtars-cli --features "uniwig igd"

Available CLI subcommands: igd, overlaprs, uniwig, bbcache, pb (fragment pseudobulking), scoring, genomicdist, ranges, consensus, prep. Flag sets differ per subcommand and evolve across versions — always confirm with gtars <command> --help.

Core Capabilities

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

1. Overlap Detection and Set Operations

Detect overlaps and compute set operations / similarity between region sets with RegionSet (Python), or index a large interval database with IGD (CLI).

When to use:

• Finding overlapping regulatory elements, comparing ChIP-seq peaks
• Variant annotation; identifying shared genomic features
• Jaccard / overlap-coefficient similarity between BED files

Quick example (Python):

from gtars.models import RegionSet

peaks = RegionSet("chip_peaks.bed")
promoters = RegionSet("promoters.bed")

# Regions in peaks that overlap a promoter (the real method is subset_by_overlaps)
in_promoters = peaks.subset_by_overlaps(promoters)
in_promoters.to_bed("peaks_in_promoters.bed")

print(peaks.count_overlaps(promoters))  # per-region overlap counts
print(peaks.jaccard(promoters))         # similarity score

For querying a large reference database many times, build an IGD index once via the CLI (gtars igd create ...) and search it (gtars igd search ...). See references/overlap.md.

2. Coverage / Accumulation Tracks (uniwig, CLI)

Generate coverage / accumulation tracks from a BED or BAM file with the uniwig CLI subcommand.

When to use:

• ATAC-seq accessibility profiles, ChIP-seq coverage, RNA-seq read coverage

Quick example (CLI):

# uniwig reads a sorted BED/BAM and writes accumulation tracks.
# Flags differ by version; confirm with `gtars uniwig --help`.
gtars uniwig --file fragments.bed --filetype bed \
             --fileheader coverage --outputtype bw

See references/coverage.md for verified flags and RegionSet.coverage() for an in-memory alternative.

3. Genomic Tokenization

Convert genomic regions into discrete tokens for ML (the preprocessing layer geniml builds on).

When to use:

• Preprocessing peaks/regions into a fixed vocabulary for genomic ML models
• Feeding token IDs to geniml or custom transformer models

Quick example (Python):

from gtars.tokenizers import Tokenizer
from gtars.models import Region

tokenizer = Tokenizer.from_bed("universe.bed")   # vocab = the universe BED
tokens = tokenizer.tokenize([Region("chr1", 1000, 2000, None)])  # -> ['chr1:1000-2000']
ids = tokenizer.convert_tokens_to_ids(tokens)                     # -> [<int>]

See references/tokenizers.md. Note: the class is Tokenizer (there is no TreeTokenizer).

4. Reference Sequence Management (refget)

Compute GA4GH refget digests and manage/retrieve reference sequences.

When to use:

• Validating reference genome integrity via sequence digests
• Building a local sequence-collection store and extracting subsequences

Quick example (Python):

from gtars import refget

# Digest a FASTA into a GA4GH SequenceCollection (no sequence data loaded)
collection = refget.digest_fasta("hg38.fa")

# Or a one-off sequence digest
d = refget.sha512t24u_digest("ACGTACGT")   # 'GS_...'-style truncated SHA-512/24

See references/refget.md for RefgetStore (load, store, and get_substring).

5. Fragment Pseudobulking (pb, CLI)

Split a single-cell fragment file into pseudobulks based on a cluster/cell-group mapping.

When to use:

• Processing single-cell ATAC-seq; cluster-based fragment aggregation

Quick example (CLI):

# The fragsplit feature exposes the `pb` (pseudobulk) subcommand.
gtars pb --fragments fragments.bed.gz --mapping cluster_mapping.tsv

The Python side also offers gtars.tokenizers.tokenize_fragment_file(...) for tokenizing fragments directly. See references/cli.md.

6. Fragment / Region Scoring

Score region/fragment files against reference datasets with the scoring CLI subcommand.

When to use:

• Evaluating enrichment of regions against a reference universe
• Batch quality-metric computation across samples

gtars scoring --help   # confirm subcommands and flags for your installed version

Common Workflows

Workflow 1: Peak Overlap Analysis

Identify peaks overlapping promoters (Python):

from gtars.models import RegionSet

peaks = RegionSet("chip_peaks.bed")
promoters = RegionSet("promoters.bed")

overlapping_peaks = peaks.subset_by_overlaps(promoters)
overlapping_peaks.to_bed("peaks_in_promoters.bed")

# Iterate results (regions expose .chr/.start/.end)
for r in overlapping_peaks:
    print(r.chr, r.start, r.end)

Workflow 2: IGD index + repeated overlap queries (CLI)

Index a large reference database once, then search it many times:

# Build the IGD database from a directory or list of BED files
gtars igd create --help     # confirm the exact input/output flags for your version

# Search the database with query regions
gtars igd search --help

Workflow 3: ML Preprocessing (tokenization)

Prepare genomic regions for an ML model:

from gtars.tokenizers import Tokenizer
from gtars.models import RegionSet

# Step 1: Build a tokenizer from the universe BED (defines the vocabulary)
tokenizer = Tokenizer.from_bed("universe.bed")

# Step 2: Tokenize a region set (tokenize accepts a RegionSet or a list of Region)
regions = RegionSet("training_peaks.bed")
tokens = tokenizer.tokenize(regions)                      # list of 'chr:start-end' strings
ids = tokenizer.convert_tokens_to_ids(tokens)             # integer IDs for the model

# Step 3: feed `ids` to geniml or a custom model (see alterlab-geniml for training)

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

• `references/python-api.md` — RegionSet / Region operations, set ops, overlaps, export
• `references/overlap.md` — overlap detection and IGD indexing
• `references/coverage.md` — uniwig coverage tracks
• `references/tokenizers.md` — region tokenization for ML
• `references/refget.md` — refget digests and RefgetStore
• `references/cli.md` — CLI subcommand overview

Relationship to geniml

gtars is the Rust performance backend for geniml (databio's ML-on-genomic-intervals library). Use gtars for the heavy interval ops and tokenization; use geniml (skill alterlab-geniml) for embedding/model training built on top of those tokens.

Data Formats

• BED: genomic intervals (3-column or extended) — the core input
• BigWig / WIG: coverage / accumulation tracks (uniwig output)
• FASTA: reference sequences (refget)
• Fragment files: single-cell fragments (often .bed.gz), with a separate cluster-mapping file for pb

Verifying the API

This package's surface differs between releases and the Python and CLI APIs are NOT mirror images. Before relying on an unfamiliar method or flag, confirm against the installed version:

uv run python -c "from gtars import models, tokenizers, refget; print(dir(models), dir(tokenizers), dir(refget))"
gtars <command> --help