Standard · SAM/BAM 1.6 · CRAM 3.1 · VCF 4.5 / BCF 2.2

GA4GH HTS Format Specifications

Maintained by GA4GH Large Scale Genomics work stream · Samtools specification community

What it helps you do

SAM/BAM · CRAM · VCF/BCF supports sequence alignments, compressed reference-oriented reads, variant calls, binary encodings, standard tags, and associated indexes.

  • Omics
PlanAcquireHarmonizeExchangeLearn + reuse

01

Where it fits and where it does not

Use these four checks before committing implementation time.

Use it when
The base interchange layer for sequencing alignments and variant-call datasets across pipelines, archives, and analysis tools.
Limits
Format conformance does not establish sample identity, consent, reference correctness, variant normalization, QC, or pipeline reproducibility. FASTQ has no formal hts-specs definition.
Best for
Omics teams working across Acquire → Harmonize → Exchange → Learn + reuse.
Maturity
EstablishedSuitable for production assessment. Pin the exact release and any implementation profile.

02

See it in the workflow

This view shows the input, the change the standard introduces, and the resulting output.

  1. InputWhat starts

    Omics source data, metadata, and local mappings

  2. SAM/BAM · CRAM · VCF/BCFWhat changes

    Use SAM/BAM · CRAM · VCF/BCF as a pinned standard across Acquire → Harmonize → Exchange → Learn + reuse

  3. OutputWhat becomes possible

    A handoff the next system or team can validate against the same release

Readiness gateFormat conformance does not establish sample identity, consent, reference correctness, variant normalization, QC, or pipeline reproducibility. FASTQ has no formal hts-specs definition.

03

A concrete example

A pipeline emits BAM or CRAM with a pinned reference checksum and validated headers, then emits normalized VCF 4.5 or BCF 2.2 with provenance, indexes, and checksums.

Why it matters: Creates stable record-level inputs for genomic feature engineering, while phenotype linkage, cohort design, QC, and leakage controls remain external.

04

What it fits with

Complements GA4GH DRS/WES: DRS locates objects, WES runs workflows, htsget streams these formats, and refget resolves reference sequences. ISA or MINSEQE carries study context.

05

Implementation starter

Start with one bounded handoff. Pin, test, and review it before scaling.

  1. Define one handoff, its accountable owner, and the decision SAM/BAM · CRAM · VCF/BCF must support.

  2. Pin the exact version and companion artifacts: SAM/BAM 1.6 · CRAM 3.1 · VCF 4.5 / BCF 2.2.

  3. Map one representative input to the required standard artifacts.

  4. Test the result against the canonical source and record every exception.

  5. Preserve the source data, mappings, and review evidence before scaling.

06

Test the main limitation

Risk

Format conformance does not establish sample identity, consent, reference correctness, variant normalization, QC, or pipeline reproducibility. FASTQ has no formal hts-specs definition.

Test

Run one representative end-to-end pilot and record exactly where SAM/BAM · CRAM · VCF/BCF loses context, needs an extension, or depends on another standard.

Risk

Machine-readable output may still be unfit for analysis or ML.

Test

Test the output for missing context, provenance, terminology alignment, time leakage, and the intended downstream decision. Creates stable record-level inputs for genomic feature engineering, while phenotype linkage, cohort design, QC, and leakage controls remain external.

07

Official resources

Specifications, diagrams, examples, and guides from the organizations that maintain them.

  • Primary sourceSAM/BAM 1.6 · CRAM 3.1 · VCF 4.5 / BCF 2.2

    GA4GH / Samtools HTS specifications

    Official publisher or steward guidance for this standard profile.

    Publisher
    GA4GH Large Scale Genomics work stream · Samtools specification community
    Open official source

Next action

Put this profile in context

Compare its role with adjacent standards or place it inside an end-to-end data pathway before choosing an implementation.