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benchmark · protocol

Zero-shot enhancer–gene linking (AlphaGenome paper)

Can the model identify which candidate regulatory elements affect a target gene?

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

2 evaluations · 2 metric rows

At a glance

Explanatory profile: limited source coverage · Automated source review, 2026-09-17. Review applies to the cited claims; unresolved fields are listed below. Numerical results retain their own review status.

Data, procedure and scoring
PropertyDescription and evidence
Dataset and biological contextENCODE-rE2G CRISPRi-validated element–gene pairs in K562, filtered for available annotations and GENCODEv46 gene identities.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
SplitZero-shot evaluation on the annotated ENCODE-rE2G pairs; do not invent a downstream supervised training split.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
Allowed inputs and adaptationReference sequence centred on the target gene, K562 RNA-seq predictions and candidate element coordinates.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
Metrics as reportedauprcAlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
AggregationauPRC over labelled element–gene pairs, with separate distance-to-TSS strata in the paper.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
UncertaintyNot reported for these summary-table scores. · Not reported in inspected sourcesAlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17
Entity typeprotocol
OrganismsNot extracted or verified for this record.
AssaysNot extracted or verified for this record.
BaselinesNot extracted or verified for this record.

How it works

Zero-shot enhancer–gene linking: evaluation procedure

Conceptual summary of the cited procedure; model-specific conditions are given below.

Zero-shot enhancer–gene linking: evaluation procedureFilter annotated element–gene pairs. Then: Compute gene-linked model evidence. Then: Normalize element scores. Then: Evaluate pair-label auPRCFilter annotated element–genepairsCompute gene-linked modelevidenceNormalize element scoresEvaluate pair-label auPRC
Read the diagram as text
  1. Filter annotated element–gene pairs
  2. Compute gene-linked model evidence
  3. Normalize element scores
  4. Evaluate pair-label auPRC
AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

What is tested

Can the model identify which candidate regulatory elements affect a target gene?

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Procedure

Compute expression input-gradient contributions near each candidate element, normalize by gene-context background gradient magnitude and impute zero for elements outside model context.

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Tested models and results

Release 2026-09-17-a757f4af4277 · 2 evaluations · 2 metric rows. Different protocols are not a single leaderboard.

Results grouped by the exact reported evaluation
Metric and findingCoverage and uncertaintyEvidence
AlphaGenome distilled all-fold student: Zero-shot enhancer–gene linking

Compute expression input-gradient contributions near each candidate element, normalize by gene-context background gradient magnitude and impute zero for elements outside model context.

Author-reported evaluation · Evaluation metadata: needs review

0.75 auprc

Unit: dimensionless · Direction: higher

Aggregation: auPRC over labelled element–gene pairs, with separate distance-to-TSS strata in the paper.

Uncertainty: unreported

Scored: Not reported · Eligible: Not reported

source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!M17

Source checking is not independent reproduction.

borzoi-ensemble (paper Table 4): Zero-shot enhancer–gene linking

Compute expression input-gradient contributions near each candidate element, normalize by gene-context background gradient magnitude and impute zero for elements outside model context.

Author-reported evaluation · Evaluation metadata: needs review

0.668 auprc

Unit: dimensionless · Direction: higher

Aggregation: auPRC over labelled element–gene pairs, with separate distance-to-TSS strata in the paper.

Uncertainty: unreported

Scored: Not reported · Eligible: Not reported

source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!L17

Source checking is not independent reproduction.

Strengths and limitations

Strengths and considerations

No source-reviewed explanatory claims are recorded here yet.

Limitations and conditions

Profile review details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Stable record: alphagenome-2026-t4-protocol-15

Evidence table

Trace each statement to its source and review. A context-only reference supports the record generally; it does not verify an individual field. Source checking does not reproduce an experiment.

One row per statement and cited source. Multiple citations are not independent evaluations. Shared locators are labelled explicitly.

42 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-09-17-a757f4af4277
Property and statementOriginal source and locationReview and provenance
Diagram caption

Conceptual summary of the cited procedure; model-specific conditions are given below.

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Retrieved page snapshot; no immutable publisher revision supplied
Retrieved: 2026-09-16T19:53:03.009088+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.caption

Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Diagram caption

Conceptual summary of the cited procedure; model-specific conditions are given below.

Individual claims
AlphaGenome Nature 2026 supplementary methods

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Supplement to Nature version of record, 28 January 2026; content hash pinned
Retrieved: 2026-09-17T06:37:01.778972+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.caption

Source artifact SHA-256: 86b2e6a07543e3c201e2e157a3e9c6eb5235ff13eb8a5224f6fcb6fe1808d4c0

Hash scope: SHA-256 of exact publisher PDF bytes

Format: original_pdf

Inspected artifact

Diagram caption

Conceptual summary of the cited procedure; model-specific conditions are given below.

Individual claims
AlphaGenome Nature 2026 supplementary comparison tables

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Nature version of record, 28 January 2026
Retrieved: 2026-09-17T06:31:06.887921+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.caption

Source artifact SHA-256: 833cb78b6ae6fe39415cfff296ac00c48d800326139f13eb307531a1cc133154

Hash scope: SHA-256 of exact retrieved original artifact bytes

Format: xlsx

Inspected artifact

Diagram steps

["Filter annotated element–gene pairs","Compute gene-linked model evidence","Normalize element scores","Evaluate pair-label auPRC"]

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Retrieved page snapshot; no immutable publisher revision supplied
Retrieved: 2026-09-16T19:53:03.009088+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.steps

Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Diagram steps

["Filter annotated element–gene pairs","Compute gene-linked model evidence","Normalize element scores","Evaluate pair-label auPRC"]

Individual claims
AlphaGenome Nature 2026 supplementary methods

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Supplement to Nature version of record, 28 January 2026; content hash pinned
Retrieved: 2026-09-17T06:37:01.778972+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.steps

Source artifact SHA-256: 86b2e6a07543e3c201e2e157a3e9c6eb5235ff13eb8a5224f6fcb6fe1808d4c0

Hash scope: SHA-256 of exact publisher PDF bytes

Format: original_pdf

Inspected artifact

Diagram steps

["Filter annotated element–gene pairs","Compute gene-linked model evidence","Normalize element scores","Evaluate pair-label auPRC"]

Individual claims
AlphaGenome Nature 2026 supplementary comparison tables

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Nature version of record, 28 January 2026
Retrieved: 2026-09-17T06:31:06.887921+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.steps

Source artifact SHA-256: 833cb78b6ae6fe39415cfff296ac00c48d800326139f13eb307531a1cc133154

Hash scope: SHA-256 of exact retrieved original artifact bytes

Format: xlsx

Inspected artifact

Diagram title

Zero-shot enhancer–gene linking: evaluation procedure

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Retrieved page snapshot; no immutable publisher revision supplied
Retrieved: 2026-09-16T19:53:03.009088+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.title

Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Diagram title

Zero-shot enhancer–gene linking: evaluation procedure

Individual claims
AlphaGenome Nature 2026 supplementary methods

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Supplement to Nature version of record, 28 January 2026; content hash pinned
Retrieved: 2026-09-17T06:37:01.778972+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.title

Source artifact SHA-256: 86b2e6a07543e3c201e2e157a3e9c6eb5235ff13eb8a5224f6fcb6fe1808d4c0

Hash scope: SHA-256 of exact publisher PDF bytes

Format: original_pdf

Inspected artifact

Diagram title

Zero-shot enhancer–gene linking: evaluation procedure

Individual claims
AlphaGenome Nature 2026 supplementary comparison tables

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Nature version of record, 28 January 2026
Retrieved: 2026-09-17T06:31:06.887921+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.diagram.title

Source artifact SHA-256: 833cb78b6ae6fe39415cfff296ac00c48d800326139f13eb307531a1cc133154

Hash scope: SHA-256 of exact retrieved original artifact bytes

Format: xlsx

Inspected artifact

Dataset and biological context

ENCODE-rE2G CRISPRi-validated element–gene pairs in K562, filtered for available annotations and GENCODEv46 gene identities.

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A17:P17; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods p.39, Enhancer-gene linking; methods: p.39, Enhancer-gene linking; paper: Fig.4j; Extended Data Fig.7a–d; tables: Suppl Table 4 Variant performan; evaluation index 15; sheet rows 17

Shared locator for this statement’s cited sources; not a separate locator for each citation.

Version: Retrieved page snapshot; no immutable publisher revision supplied
Retrieved: 2026-09-16T19:53:03.009088+00:00

source checked

automated source review · 2026-09-17

Audit details

Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.

Field: attributes.profile.facts.0.value

Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Sources and history

Release 2026-09-17-a757f4af4277 · Record review: needs review

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Technical metadata and extraction receipts

Stable ID: alphagenome-2026-t4-protocol-15

areas
dna-genomes
entity level
protocol
version
Nature version of record, 28 January 2026
source evaluation index
15
source table
4
reference levels
metric: auprc; printed value: 0.045; numeric value: 4.4999999999999998E-2; source locator: Suppl Table 4 Variant performan!J17; note: Source reference quantity for relative-performance calculation, not a measured baseline run.
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