Data Readiness
Knowledge BaseLife-sciences R&D
54 profiles ·
source-checked 13 Jul 2026

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

Use SAM/BAM · CRAM · VCF/BCF when you need 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 doesn’t

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.
Do not use it as
Do not treat SAM/BAM · CRAM · VCF/BCF as a complete solution on its own. 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
Teams working with Omics data across Acquire → Harmonize → Exchange → Learn + reuse.
Maturity
EstablishedEstablished enough for serious use; still pin the exact release and any implementation profile.

02

See it in the workflow

A standard creates value by changing a handoff, not by existing in a catalog.

  1. InputWhat starts

    Omics data, metadata, and the local decisions around them

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

    SAM/BAM · CRAM · VCF/BCF applies a shared standard across Acquire → Harmonize → Exchange → Learn + reuse

  3. OutputWhat becomes possible

    A more consistent, reviewable handoff for the next system or team

Readiness gateBefore scaling: Format 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. Name an 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

Limitation to test first—and the tests that catch it

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

A structured or machine-readable result can still be unfit for analysis or AI.

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

Why we believe this

Checked against the canonical source plus independent operational evidence from an adopter, regulator, or implementation report.

Evidence notation: E1 + E2. The code is shorthand; the plain-language statement above is the claim.

Formal status
Current canonical family; SAM/BAM 1.6, CRAM 3.1, VCF 4.5 / BCF 2.2
Confidence
High
Review state
Source-checked
Reviewed by
Genomic formats reviewer
Last verified
13 July 2026
Review again when
Any SAM, CRAM, VCF/BCF, tag, index, htsget, or refget specification update
How the evidence method works

08

Source shelf

Official diagrams, examples, specifications, and explainers. Nothing external loads until you choose to open it.

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

    GA4GH / Samtools HTS specifications

    The canonical publisher or steward source used to verify this standard profile.

    Publisher
    GA4GH Large Scale Genomics work stream · Samtools specification community
    Rights
    Rights remain with the publisher; this knowledge base links to the source rather than copying it.
    Access
    Opens the publisher's source in a new tab; no external media loads on this page.
    Verified
    2026-07-13
    Open at 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.