tiledbvcf – skill Dữ liệu & Khoa học cho agent AI

TileDB-VCF

When to use

Use for cohort variant storage, incremental sample ingestion, interval queries, and

exporting subsets for downstream genomics. TileDB-VCF stores records; it does not

perform joint variant calling, association testing, normalization, or population

structure adjustment. Dataset size alone does not determine whether cloud execution

is appropriate: benchmark the intended sample, region, and attribute workload.

This skill targets released TileDB-VCF 0.40.3. Native Python/CLI checks used two

synthetic single-sample VCFs on macOS ARM64. Cloud client 0.14.4 contracts were

checked against its released wheel and mocked dispatch; hosted queries and jobs

were not executed. See [installation and verification notes](references/verification.md).

Install and verify the native stack

The tiledbvcf Python distribution is not published on PyPI at this review. The

official tiledb Conda channel supplies tiledbvcf-py 0.40.3 for macOS ARM64,

macOS x86-64, and Linux x86-64, with Python 3.9-3.12 builds. tiledb on PyPI is

TileDB-Py and does not install TileDB-VCF. Native Apple Silicon no longer requires

forcing CONDA_SUBDIR=osx-64.

For the tested macOS ARM64 environment, pins below avoid versioned-library import

failures in the otherwise successful current Conda solve:

conda create -n tiledb-vcf -c tiledb -c conda-forge \
  python=3.12 tiledbvcf-py=0.40.3 \
  azure-core-cpp=1.16.2 azure-storage-blobs-cpp=12.16.0 \
  azure-storage-files-datalake-cpp=12.14.0 capnproto=1.4.0 c-blosc2=2.23.1
conda activate tiledb-vcf
python -c 'import tiledbvcf; print(tiledbvcf.version)'
tiledbvcf version

The equivalent Micromamba solve/install was executed. These extra ABI pins are a

verified macOS ARM64 workaround, not a claim about all platforms. Preserve the

resolved environment for production. Other-platform installation and official

Docker images are alternatives documented upstream, not tested here.

Prepare and create a cohort

1. Record reference assembly, contig naming/lengths, callers, normalization rules,

sample identity, and file checksums. Do not mix assemblies or assume 1 and

chr1 are equivalent. Confirm compatible headers across inputs.

2. Each input must contain one sample, be coordinate sorted, and have an index.

Use BGZF-compressed VCF or BCF with a matching .csi/.tbi. Inspect

bcftools query -l sample1.vcf.gz; filenames are not sample identifiers.

3. Create the dataset explicitly, then ingest. Opening mode="w" alone does not

create its schema. Materialize frequently read fields at creation time.

4. Validate a small known interval and a round-trip export before scaling.

For existing sorted plain-text VCFs (run once per input; output names must be new):

bcftools view -Oz -o sample1.vcf.gz sample1.vcf
bcftools index -c sample1.vcf.gz
bcftools view -Oz -o sample2.vcf.gz sample2.vcf
bcftools index -c sample2.vcf.gz

The following local examples were exercised with sample IDs S1 and S2, contig

chr1, and coordinates 1-100; substitute the verified IDs and intervals in real data.

import tiledbvcf

uri = "cohort"
config = {"sm.compute_concurrency_level": "2", "sm.io_concurrency_level": "2"}
with tiledbvcf.Dataset(uri, mode="w", tiledb_config=config) as ds:
    ds.create_dataset(extra_attrs=["fmt_GT", "fmt_DP"])
    ds.ingest_samples(
        ["sample1.vcf.gz"], threads=2, total_memory_budget_mb=512
    )

# Incremental ingestion uses the existing dataset; do not call create_dataset again.
with tiledbvcf.Dataset(uri, mode="w", tiledb_config=config) as ds:
    ds.ingest_samples(
        ["sample2.vcf.gz"], threads=2, total_memory_budget_mb=512
    )

The schema-v4 data array has contig, start-coordinate, and sample dimensions;

headers and optional statistics are separate arrays in the dataset group. Fields

not explicitly materialized remain in the INFO/FORMAT payloads. Query names such

as pos_start need not match raw storage column names.

Upstream supports parallel thread/process ingestion. Assign distinct sample work

and coordinate lifecycle/maintenance operations; do not blindly re-ingest samples.

resume=True supports interrupted ingestion, not arbitrary duplicate correction.

Query completely and interpret coordinates correctly

| Surface | Coordinate convention |

| --- | --- |

| Python regions=["chr1:10-14"] | 1-based, closed interval |

| Returned pos_start, pos_end | 1-based, inclusive record endpoints |

| BED input and query_bed_start, query_bed_end | 0-based, half-open |

| read_variant_stats() / read_allele_count() column pos in 0.40.3 | 0-based; add one before joining to VCF POS |

Queries return overlapping records, not just records starting inside the

interval. A deletion spanning positions 10-14 appears in chr1:14-14, with

pos_start=10. For BED [13,14), the equivalent string is chr1:14-14.

The Python region parser requires explicit contig:start-end; bare "chr1"

is rejected in this release. Use a known contig length for a whole-contig query.

cfg = tiledbvcf.ReadConfig(memory_budget_mb=128, tiledb_config=config)
attrs = ["sample_name", "contig", "pos_start", "pos_end", "alleles", "fmt_GT"]
with tiledbvcf.Dataset(uri, cfg=cfg) as ds:
    assert {"S1", "S2"}.issubset(ds.samples())
    assert set(attrs).issubset(ds.attributes())
    for batch in ds.read_iter(
        attrs=attrs, regions=["chr1:1-100"], samples=["S1", "S2"]
    ):
        print(batch)  # Replace with a bounded consumer or partitioned output.

• read() returns a pandas DataFrame; read_arrow() returns a PyArrow Table.

Either can return only the first memory-limited batch. Continue with

continue_read() / continue_read_arrow() until read_completed(), or use

read_iter() for ordinary DataFrame queries. Avoid concatenating all batches

when the result cannot fit in memory.

• ReadConfig(memory_budget_mb=...) controls reads; use

ingest_samples(total_memory_budget_mb=...) for writes. A read budget is not

a process RSS cap. limit truncates total output; it is not a pagination size.

• sample_partition=(0, 2) selects partition zero of two. Likewise,

region_partition=(index, number_of_partitions) partitions query regions;

these tuples are not coordinate bounds, tile extents, or sample capacities.

• 0.40.3 retains BED selection state when a later call omits bed_file.

Open a fresh Dataset for an independent query when changing BED/region inputs.

• fmt_GT contains allele indices: 0 refers to REF, positive values index ALT,

and -1 means missing. Preserve multiallelic identity and ploidy; do not treat

every positive integer as a biallelic dosage or missing calls as reference.

The integer list alone does not encode the original phased GT string.

Export and validate

from pathlib import Path

Path("exported").mkdir(exist_ok=True)
with tiledbvcf.Dataset(uri, cfg=cfg) as ds:
    ds.export(
        samples=["S1"], regions=["chr1:1-100"],
        output_format="v", output_dir="exported",
    )

Python export formats: v VCF, z compressed VCF, u uncompressed BCF, b

compressed BCF. merge=False writes per-sample files; merge=True requires a

combined output_path. A combined export is not joint calling. Re-index exported

files before indexed downstream access. Compare sample IDs, contigs, record

counts, alleles, INFO/FORMAT values, and missing/phased genotypes; semantic

round-trip preservation does not imply byte-identical compression or headers.

The CLI accepts positional sample paths or --samples-file (one URI per line),

not a comma-separated --samples argument:

tiledbvcf create --uri cli_cohort
tiledbvcf store --uri cli_cohort --threads 2 --total-memory-budget-mb 512 \
  -- sample1.vcf.gz sample2.vcf.gz
tiledbvcf list --uri cli_cohort
tiledbvcf stat --uri cli_cohort
tiledbvcf export --uri cli_cohort --regions chr1:1-100 \
  --sample-names S1,S2 -Ot --tsv-fields 'SAMPLE,CHR,POS,REF,ALT,F:GT' \
  --output-path variants.tsv

-- protects positional paths from variable-length options such as

--tiledb-config. Check expected artifacts and sample counts as well as the exit

code: an invalid store command returned exit zero while printing an error in the

reviewed CLI. TSV fields use F:GT for FORMAT/GT and I:DP for INFO/DP.

Cohort statistics and QC

with tiledbvcf.Dataset(uri, cfg=cfg) as ds:
    stats = ds.read_variant_stats(regions=["chr1:1-100"], drop_ref=True)
    stats["vcf_pos"] = stats["pos"] + 1
    print(stats[["contig", "vcf_pos", "alleles", "ac", "an", "af"]])

qc = tiledbvcf.sample_qc(uri, samples=["S1"], config=config)
print(qc)

Statistics arrays are enabled by default at creation; older/disabled arrays may

not support these operations. read_variant_stats has no samples argument.

The older read_allele_frequency(dataset_uri, region) wrapper accepts a single

region and delegates to the

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