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benchmark · protocol

Author MFASS splice-disruption prediction (AlphaGenome paper)

Can sequence-derived splicing changes predict experimentally measured exon disruption in MFASS?

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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 contextMFASS reporter-assay SNVs processed using the MMSplice-paper MFASS notebook; mislabelled strands removed. The paper’s cleaned-dataset totals are not a reported test-subset count.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
SplitZero-shot scorer development uses validation chromosomes 1,2,4,5,7,8,10,11,13,14,15,17,20,22,X; final test chromosomes are 3,6,9,12,16,18,19,21. This partitions variant evaluation labels; the distilled model’s teachers were trained on all reference-genome folds.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
Allowed inputs and adaptationREF/ALT sequence, the assayed exon’s donor/acceptor identity and paper-specific splicing-head scores.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
Metrics as reportedall_tissues_auprcAlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
AggregationauPRC for the splice-disrupting label defined by the MFASS exon-inclusion threshold.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
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'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
Entity typeprotocol
OrganismsNot extracted or verified for this record.
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BaselinesNot extracted or verified for this record.

How it works

Author MFASS splice-disruption prediction: evaluation procedure

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

Author MFASS splice-disruption prediction: evaluation procedureClean author MFASS labels. Then: Apply author chromosome partition. Then: Compute exon-specific composite score. Then: Average tissues and evaluate auPRCClean author MFASS labelsApply author chromosomepartitionCompute exon-specific compositescoreAverage tissues and evaluateauPRC
Read the diagram as text
  1. Clean author MFASS labels
  2. Apply author chromosome partition
  3. Compute exon-specific composite score
  4. Average tissues and evaluate auPRC
AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

What is tested

Can sequence-derived splicing changes predict experimentally measured exon disruption in MFASS?

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

Procedure

Use the MFASS-specific donor/acceptor and junction scoring procedure, sum splicing components, then average across tissues. Compare with the source’s exon-inclusion disruption label.

AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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: Author MFASS splice-disruption prediction

Use the MFASS-specific donor/acceptor and junction scoring procedure, sum splicing components, then average across tissues. Compare with the source’s exon-inclusion disruption label.

Author-reported evaluation · Evaluation metadata: needs review

0.51 all_tissues_auprc

Unit: dimensionless · Direction: higher

Aggregation: auPRC for the splice-disrupting label defined by the MFASS exon-inclusion threshold.

Uncertainty: unreported

Scored: Not reported · Eligible: Not reported

source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!M8

Source checking is not independent reproduction.

Pangolin (paper Table 4): Author MFASS splice-disruption prediction

Use the MFASS-specific donor/acceptor and junction scoring procedure, sum splicing components, then average across tissues. Compare with the source’s exon-inclusion disruption label.

Author-reported evaluation · Evaluation metadata: needs review

0.541972 all_tissues_auprc

Unit: dimensionless · Direction: higher

Aggregation: auPRC for the splice-disrupting label defined by the MFASS exon-inclusion threshold.

Uncertainty: unreported

Scored: Not reported · Eligible: Not reported

source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!L8

Source checking is not independent reproduction.

Strengths and limitations

Strengths and considerations

No source-reviewed explanatory claims are recorded here yet.

Limitations and conditions

  • This is the author’s MFASS analysis, not rewire MFASS v2. The methods first prescribe logits, then describe probability/usage differences; do not silently reconstruct an exact scorer implementation from this wording. Do not assign cleaned full-dataset counts to its held-out test subset.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
  • This is an author-reported protocol, not a rewire rerun. Different datasets, processing and adaptations cannot support an unrestricted leaderboard.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8
Profile review details

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Stable record: alphagenome-2026-t4-protocol-7

Evidence table

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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'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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.

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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'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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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'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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

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

Format: xlsx

Inspected artifact

Diagram steps

["Clean author MFASS labels","Apply author chromosome partition","Compute exon-specific composite score","Average tissues and evaluate auPRC"]

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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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.

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Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Diagram steps

["Clean author MFASS labels","Apply author chromosome partition","Compute exon-specific composite score","Average tissues and evaluate auPRC"]

Individual claims
AlphaGenome Nature 2026 supplementary methods

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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source checked

automated source review · 2026-09-17

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Hash scope: SHA-256 of exact publisher PDF bytes

Format: original_pdf

Inspected artifact

Diagram steps

["Clean author MFASS labels","Apply author chromosome partition","Compute exon-specific composite score","Average tissues and evaluate auPRC"]

Individual claims
AlphaGenome Nature 2026 supplementary comparison tables

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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source checked

automated source review · 2026-09-17

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

Format: xlsx

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Diagram title

Author MFASS splice-disruption prediction: evaluation procedure

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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Retrieved: 2026-09-16T19:53:03.009088+00:00

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Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

Inspected artifact

Diagram title

Author MFASS splice-disruption prediction: evaluation procedure

Individual claims
AlphaGenome Nature 2026 supplementary methods

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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

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Hash scope: SHA-256 of exact publisher PDF bytes

Format: original_pdf

Inspected artifact

Diagram title

Author MFASS splice-disruption prediction: evaluation procedure

Individual claims
AlphaGenome Nature 2026 supplementary comparison tables

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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

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

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Source artifact SHA-256: 833cb78b6ae6fe39415cfff296ac00c48d800326139f13eb307531a1cc133154

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

Format: xlsx

Inspected artifact

Dataset and biological context

MFASS reporter-assay SNVs processed using the MMSplice-paper MFASS notebook; mislabelled strands removed. The paper’s cleaned-dataset totals are not a reported test-subset count.

Individual claims
alphagenome: Journal full-text XML

Original source ↗

'Suppl Table 4 Variant performan'!A8:P8; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.31–32, MFASS; methods: pp.31–32, MFASS; paper: Fig.3i; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 7; sheet rows 8

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.

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Source artifact SHA-256: d159b791fc6cb7b679c151727b7b05a6e5b6388b08a89b675014983d85b6df36

Hash scope: SHA-256 of retrieved original artifact bytes

Format: original_artifact

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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-7

areas
dna-genomes
entity level
protocol
version
Nature version of record, 28 January 2026
source evaluation index
7
source table
4
reference levels
metric: all_tissues_auprc; printed value: 0.02; numeric value: 0.02; source locator: Suppl Table 4 Variant performan!J8; note: Source reference quantity for relative-performance calculation, not a measured baseline run.
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