AlphaGenome Sequences And Outputs¶

This guide covers the practical AlphaGenome inputs used by genomics alphagenome ... and by dataset builders that call AlphaGenome internally.

Commands¶

genomics alphagenome analyze -- -i sequence.fasta -k API_KEY -o results/
genomics alphagenome integrate -- --integrated --vcf vcf/sample.vcf.gz --ref refs/GRCh38.fa --api-key API_KEY --output integrated_analysis/
genomics alphagenome tracks --api-key API_KEY --output configs/workflows/alphagenome/tracks.json

Arguments after -- are forwarded to the underlying AlphaGenome modules.

Supported Sequence Sizes¶

AlphaGenome accepts a fixed set of sequence lengths:

Length	Typical Use
2,048 bp	Small windows and quick tests.
16,384 bp	Individual genes or local regulatory regions.
131,072 bp	Larger genes, gene clusters, and broad regulatory regions.
524,288 bp	Large loci and regional context.
1,048,576 bp	Megabase-scale context and contact-map-style analyses.

Check FASTA length before submitting:

grep -v "^>" sequence.fasta | tr -d '\n' | wc -c

If a sequence is shorter than the target length, pad with N. If it is longer, crop around the variant, gene, or region of interest. For variant analysis, center the variant whenever possible.

Getting Sequences¶

You can extract real genomic sequence from Ensembl, UCSC, NCBI, or a local indexed reference. Keep the assembly consistent with downstream VCFs and annotations.

Example Ensembl REST request for a 2,048 bp GRCh38 interval:

curl 'https://rest.ensembl.org/sequence/region/human/11:5227002..5229049?coord_system_version=GRCh38' \
  -H 'Content-type:text/x-fasta' > HBB_2048bp.fasta

Example local reference extraction:

samtools faidx GRCh38.fa chr11:5227002-5229049 > HBB_2048bp.fasta

Before use, confirm that the FASTA contains only expected bases (A, C, G, T, and optionally N) and that the length is one of the supported sizes.

Output Families¶

AlphaGenome output names are families, not individual assays. Common families include:

Output	Meaning
`RNA_SEQ`	Gene expression signal.
`CAGE`	Transcription start site activity.
`PROCAP`	Precision run-on transcription initiation signal.
`ATAC`	Chromatin accessibility.
`DNASE`	DNase hypersensitivity/accessibility.
`CHIP_HISTONE`	Histone modification tracks such as H3K27ac and H3K4me3.
`CHIP_TF`	Transcription factor tracks such as CTCF.
`CONTACT_MAPS`	Chromatin contact predictions.
`SPLICE_JUNCTIONS`	Splice junction predictions.
`SPLICE_SITES`	Donor/acceptor splice site predictions.
`SPLICE_SITE_USAGE`	Splice site usage predictions.

Use family names in commands:

genomics alphagenome analyze -- \
  -i sequence.fasta \
  -k API_KEY \
  -o results/ \
  --outputs RNA_SEQ ATAC CHIP_HISTONE

Do not request individual names such as H3K27AC directly. Use CHIP_HISTONE or CHIP_TF and select ontology/track metadata downstream when supported.

Track And Ontology Discovery¶

Export available output and ontology metadata with:

genomics alphagenome tracks --api-key API_KEY --output configs/workflows/alphagenome/tracks.json

For diagnostics outside the CLI, use:

python scripts/diagnostics/check_alphagenome_outputs.py
python scripts/diagnostics/check_dna_client_methods.py

The exported metadata helps choose genotype predictor config fields such as:

dataset_input:
  alphagenome_outputs: ["RNA_SEQ"]
  ontology_terms: ["UBERON:0000955"]

Recommended Output Sets¶

Use Case	Outputs
Quick smoke test	`RNA_SEQ`
Expression and promoters	`RNA_SEQ CAGE PROCAP`
Regulatory variant analysis	`RNA_SEQ CAGE ATAC CHIP_HISTONE`
Chromatin accessibility	`ATAC DNASE`
Epigenetic state	`CHIP_HISTONE CHIP_TF`
Splicing	`RNA_SEQ SPLICE_JUNCTIONS SPLICE_SITES SPLICE_SITE_USAGE`
3D context	`CONTACT_MAPS CHIP_TF`

More outputs increase runtime and storage. For large sequence lengths, start with a narrow output set and expand only after the workflow is validated.

Relationship To Legacy Guides¶

Older notes remain in the repository for provenance:

docs/historical/alphagenome/DOWNLOAD_SEQUENCES.md
docs/historical/alphagenome/AVAILABLE_OUTPUTS.md
docs/historical/alphagenome/SUPPORTED_SIZES.md
docs/historical/APPLIED_FIXES.md

Use this page as the active guide for new runs.