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High-performance BGEN reader with cloud (GCS/S3) partial-read support

Project description

lazybgen

CI Wheels PyPI License: MIT

High-performance BGEN reader with Google Cloud Storage and Amazon S3 partial-read support. lazybgen reads only the variants or regions you ask for, fetching them directly from local files, GCS, or S3 via random-access byte-range reads, so there is no need to download the whole file.

It is a Cython/C++ implementation with vendored, optimized compression backends (zlib-ng and zstd) compiled from source for consistent cross-platform behavior and speed (SIMD genotype parsing, parallel block decompression).

Install

pip install lazybgen

For Amazon S3 support, install the s3 extra:

pip install lazybgen[s3]

From source

git clone --recursive https://github.com/mkanai/lazybgen.git
cd lazybgen
pip install .

Building from source requires a C++ compiler and CMake (pip install cmake). The vendored zlib-ng and zstd are git submodules, so clone with --recursive (or run git submodule update --init --recursive).

Usage

from lazybgen import load_bgen

# Local file
genotypes, variant_info, sample_ids = load_bgen(
    "chr1.bgen",
    region="chr1:1000000-2000000",   # partial read: only this region is fetched
)

# GCS (default credentials)
load_bgen("gs://bucket/file.bgen", index_path="gs://bucket/file.bgen.bgi")

# GCS requester-pays bucket. True bills the default project from your environment
load_bgen("gs://bucket/file.bgen", storage_options={"requester_pays": True})
# ...or pass a project id string to bill a specific project
load_bgen("gs://bucket/file.bgen", storage_options={"requester_pays": "my-billing-project"})

# Public S3 bucket (anonymous, no credentials)
load_bgen("s3://bucket/file.bgen", storage_options={"anon": True})

load_bgen returns (genotypes, variant_info, sample_ids), where genotypes is an (n_samples, n_variants) np.ndarray, variant_info is a pd.DataFrame with columns chrom, pos, rsid, ref, alt, and sample_ids is a list[str].

A .bgi index is required; create one with bgenix -g file.bgen.

Parameters

  • file_path: path, gs://, or s3:// URL to the BGEN file
  • index_path: .bgi index (defaults to file_path + ".bgi")
  • sample_path: optional .sample file
  • region: "chr:start-end" to read a genomic interval
  • variant_filter: variant subset as a dict; build it with load_variant_filter("variants.z"), which reads variant IDs/positions from a .z file (from lazybgen import load_variant_filter)
  • sample_ids: subset of samples to load
  • dtype: dosage dtype (default float64). np.float32 decodes ~18% faster and uses half the memory; use it when single precision is sufficient (dosages are computed in single precision regardless, so float64 output is the exact widening of the float32 result)
  • show_progress: show a progress bar while loading (default False)
  • nan_action: how to handle missing dosages: "error" (default, raise), "mean" (impute with the per-variant mean), "omit" (drop affected samples), or "warn" (keep NaNs and log a warning)
  • num_threads: worker threads for decoding. 0 (default) auto-detects the CPU core count and decodes blocks in parallel; 1 forces single-threaded decoding; N > 1 uses N threads (see Parallel decode)
  • storage_options: backend kwargs forwarded to the fsspec filesystem (e.g. {"anon": True} for public S3, {"requester_pays": True} to bill the env default project, or {"requester_pays": "billing-project-id"} for GCS requester-pays buckets)

Supported BGEN features

lazybgen computes alt-allele dosages and targets the most common BGEN profile:

Feature Support
Layout v1.2 / v1.3 Yes
Layout v1.1 Best-effort
Compression: zlib, zstd Yes
Compression: none (uncompressed) No
Biallelic, diploid (phased or unphased) Yes
Multi-allelic (>2 alleles) No
Non-diploid (ploidy != 2) No

Unsupported inputs raise a clear error rather than returning wrong dosages. Compress uncompressed files with bgenix or qctool2 first.

Layout v1.1 is an older format with a different probability encoding; lazybgen decodes it through a separate, less-exercised path, so it is best-effort. Prefer v1.2 / v1.3 (re-encode with qctool2 if needed) for production use.

Build info

from lazybgen import get_build_info returns the compression backend the package was built against (vendored zlib-ng / zstd, or system libraries).

Remote .bgi index caching

For a gs:///s3:// BGEN, the genotype data is read in place via byte ranges, but the .bgi index is downloaded once to a local cache. The cache lives in a dedicated directory (a lazybgen-bgi-cache subdirectory of the system temp dir) and each entry is keyed by a hash of the full URL, so same-named indexes in different buckets never collide. Override the location with the LAZYBGEN_BGI_CACHE_DIR environment variable.

Streaming large files

load_bgen materializes the whole (n_samples, n_variants) matrix. For files too large to hold at once, BgenReader.iter_variants() streams variants in memory-bounded blocks (peak memory O(n_samples × block_size)). It yields (info, dosage) per variant, where info is a dict with keys chrom, pos, rsid, ref, alt (access as info["chrom"]) and dosage is a 1-D array of per-sample dosages (NaN for missing):

from lazybgen.reader import BgenReader

with BgenReader("chr1.bgen") as reader:
    for info, dosage in reader.iter_variants():
        ...  # info["pos"]; dosage.shape == (reader.nsamples,)

It accepts the same region_chrom/region_start/region_end, variant_filter, sample_indices, and dtype selection as load_variants. By default block_size auto-scales to keep each block near a fixed memory budget (it shrinks as the sample count grows); pass an explicit block_size to override.

Parallel decode

Decoding runs in parallel across CPU cores by default: each block is inflated and decoded across worker threads, byte-identical to single-threaded decoding. This applies to load_bgen, BgenReader.load_variants, and iter_variants, for both all-samples and sample-filtered (cohort) reads, and scales with the sample and core count (e.g. ~5x faster on a 100K-sample load on a 16-core machine, ~3.7x on a cohort).

Control the worker count with num_threads: 0 (default) auto-detects the core count, 1 forces single-threaded decoding, and N > 1 uses N threads.

# Parallel by default (auto-detected cores)
genotypes, variant_info, sample_ids = load_bgen("chr1.bgen")

# Force single-threaded decoding
load_bgen("chr1.bgen", num_threads=1)

# BgenReader takes the same num_threads control
with BgenReader("chr1.bgen", num_threads=8) as reader:
    dosages, info = reader.load_variants(region_chrom="chr1", region_start=1, region_end=1_000_000)

Performance

lazybgen vs the bgen package reading the same local files (16 vCPU / 128 GB VM, median of 3 page-cache-warm runs). Variant count fixed at 10k, samples scaling to biobank size; speedup is lazybgen vs bgen, parenthetical is lazybgen's wall time:

Workload 5k x 10k (94 MB) 50k x 10k (931 MB) 500k x 10k (9.1 GB)
Full decode 2.6x (0.31 s) 3.5x (2.1 s) 3.8x (19.4 s)
Region (500 variants) 2.7x (16 ms) 3.7x (100 ms) 3.7x (1.07 s)
Scattered (200 variants) 2.6x (7 ms) 3.3x (51 ms) 3.3x (486 ms)

Remote: lazy partial reads at biobank scale

A local-only reader must download the whole file before reading a byte; lazybgen fetches only the variants you ask for, directly from gs://, in time that depends on the sample count and the number of variants requested - not the file size. So as a file grows toward biobank-scale variant counts, lazybgen's partial-read time stays flat while the download baseline grows. At 500k samples:

Read (500k samples) lazybgen gs:// 10k var (9.1 GB) 50k var (45 GB) 100k var (91 GB)
One variant 0.32 s ~25x (8 s) ~100x (33 s) ~265x (85 s)
Region (500 contiguous) 5.4 s ~2.2x (12 s) ~6.9x (37 s) ~17x (89 s)
Scattered (200 random) 12.1 s ~0.8x (10 s) ~2.9x (35 s) ~7x (87 s)

Each cell is the end-to-end speedup, with the download-then-read baseline time in parentheses (whole-file gcloud storage cp + bgen's local read). All three download sizes are measured (same-region, ~1.2 GB/s); lazybgen's partial-read times are measured and size-invariant. This is best-case for the download (fast same-region link, free egress), so a laptop/cross-region/metered link widens every gap. See benchmarks/README.md for the full size ladder, wall times, invariance check, and methodology.

License

MIT

Citation

Kanai, M. et al. Population-scale multiome immune cell atlas reveals complex disease drivers. medRxiv (2025)

Contact

Masahiro Kanai (mkanai@broadinstitute.org)

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The following attestation bundles were made for lazybgen-0.1.0-cp39-cp39-musllinux_1_2_x86_64.whl:

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The following attestation bundles were made for lazybgen-0.1.0-cp39-cp39-manylinux_2_28_x86_64.whl:

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The following attestation bundles were made for lazybgen-0.1.0-cp39-cp39-macosx_11_0_arm64.whl:

Publisher: wheels.yml on mkanai/lazybgen

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