Cybergenic
All findings

SF3B1 ⊥ BAP1

SF3B1 and BAP1 mutual exclusivity in melanoma (MSK-IMPACT 50K)

Inconclusive: differs between strataMutual exclusivity · Evidence: pattern across patients, not yet tested within subtypes

DataMSK-IMPACT 50K (2026) · Melanoma · 1,644 tumours · both altered in 3 (3.9 expected if independent)

Engine's conclusion

Inconclusive. Significant, but the effect differs between tumour types or subtypes, so it is not one general relationship across this cancer.

A well-studied pair (630 papers): on the map it is known biology, a positive control rather than an overlooked discovery.

Statistical support50%Significance (FDR q)0.00059Signal (x)8%Efficacy (y)0%

Signal (x) is the corrected significance on the map's scale, discounted from 38% to 8% because the cohort-composition confound is not yet controlled. Efficacy (y) is credibility times actionability.

Structure & site3D structure: AlphaFold

These genes are rarely altered in the same tumour: mutual exclusivity, often a sign they hit one shared pathway so a tumour needs only one broken.

Primary site

Skin (melanoma)

This finding's tumour type arises in the highlighted organ.

No structure profile is curated for this gene.

SF3B1Gene

A human gene in this finding. Not in the curated driver set, so no structured profile is shown.

SF3B1 mutations in melanoma →SF3B1 co-mutations by tumour type →Other findings with SF3B1 →

No structure profile is curated for this gene.

BAP1Gene

A human gene in this finding. Not in the curated driver set, so no structured profile is shown.

BAP1 mutations in melanoma →BAP1 co-mutations by tumour type →Other findings with BAP1 →

Anatomical figure from the EBI Expression Atlas anatomogram, and predicted structures from the AlphaFold Protein Structure Database (both CC-BY-4.0). A model shows the protein's healthy fold; a highlighted residue marks a recurrent cancer position, not a prediction of a specific mutation's effect.

Statistical evidence
Test p (raw)
4.2 × 10-7
Effect (log₂ odds ratio)
-2.2
Papers
630
Abstracts naming both
129
Trials
0
Contingency table: the source of the q1,644 tumours

The raw 2×2 the FDR q and log₂ odds ratio above were computed from. It is the immutable evidence the score re-derives from: every number on this page traces back to these four counts.

Gene stateSF3B1 alteredSF3B1 wild-type
BAP1 altered360
BAP1 wild-type1001,481

both 3 (expected 3.9 if independent) · BAP1-only 60 · SF3B1-only 100 · neither 1,481

Sources
cBioPortal / MSK-IMPACT 50K (2026)Genome NexusOmniPath / Reactome / STRINGUCSC XenaOpen TargetsPubTator3NIH iCiteEurope PMCClinicalTrials.gov
Anytime-valid evidence (e-value)e = 21

Strong evidence. Exceeds the α=0.05 reject threshold (e≥20). Unlike a single-look p, this stays valid under the engine's continuous re-testing.

Why it sits here on the map

Molecular-subtype certification is unresolved. Recorded lineage only. Within-lineage molecular subtype remains unresolved. The association remains visible, but does not qualify as a subtype-controlled discovery.

Opacity: novelty (display only)15%

The two axes are variables: signal (x) and efficacy (y = credibility × actionability). A point high on both lands in the frontier (top-right). A strong signal with low credibility sits low and to the right: statistically strong, not worth pursuing.

SF3B1BAP1
Same question in other cohorts
HypothesisModel-generated hypothesis (not evidence)
Written by gpt-6-luna

A language model wrote this from the evidence listed below. It is annotation: the engine's verdict above comes only from the measured statistics, never from this text.

The most likely explanation is that SF3B1 and BAP1 alterations are enriched in different molecular subtypes of melanoma, producing apparent population-level mutual exclusivity rather than demonstrating functional redundancy or negative selection within individual tumours.

Argument strength (model self-report)18%
After adversarial review18%
The argument
  1. 1The depletion is statistically robust after adjustment for overall alteration burden (FDR q=5.9e-4), and its estimated effect is substantial (within-stratum log2 odds ratio -2.2, 95% CI -3.5 to -0.9). However, only three tumours carry both alterations, so the effect estimate may be unstable.E1E18
  2. 2Subtype composition is the leading explanation because molecular subtype remains unresolved and the measured heterogeneity is stratum-specific. The analysis accounts for tumour alteration burden and records lineage, but does not rule out differences among molecular subtypes.E1E2
  3. 3This lead CONVERGES with the prior Cybergenic SF3B1–BAP1 melanoma finding, which also favoured residual molecular-subtype composition. That is convergence with a prior interpretation, not independent replication; the other corpus findings concern different gene pairs and do not directly corroborate this pair-specific hypothesis.E14E15E16E17
  4. 4The supplied paper abstracts do not establish a functional relationship between SF3B1 and BAP1: the cited CMMN and uveal-melanoma abstracts do not report testing this pair. Thus the co-mentions do not support a within-tumour mechanism; the direct mechanistic claim remains under-explored despite the literature co-mentions.E8E9E10
  5. 5The strongest deflating explanation is cohort-specific signal or winner's-curse bias: the association has not recurred in another independent patient source. This limits confidence even though the FDR-adjusted signal is strong.E3E18
What would confirm or refute it

In an independent melanoma cohort with molecular-subtype annotations, perform a prespecified subtype-stratified analysis of SF3B1–BAP1 co-alteration, adjusting for alteration burden. Attenuation of the depletion within subtypes would support subtype composition as the leading explanation; persistence would weaken it, but would not by itself establish within-tumour cooperation or negative selection.

Strongest competing explanation (model)

This is a population-level hypothesis, not evidence that the alterations interact within the same tumour. Molecular subtype is unresolved, only three double-altered tumours are observed, and the signal has not replicated across sources. The prior corpus finding is convergent but not independent confirmation. No supplied paper abstract actually studies the SF3B1–BAP1 relationship, so a within-tumour mechanism is intentionally left unspecified.

Adversarial review (second model pass)

Weakest link: The subtype explanation is not supported by subtype-resolved data, and the apparent depletion is confined to one cohort with only three double-altered tumors and no cross-cohort replication.

Cross-cohort agreement (intra-snapshot)single source

Significant (after FDR correction) in one independent source of this tumour type so far. The engine records where a pattern is significant, not every source that could test it, so this calls for caution: a pattern selected from many tests tends to overstate its effect. It does not count against the pattern.

Evidence the argument cites

Model-written annotation, not a finding. The statistics it cites are real and are shown above; the argument connecting them is a hypothesis that needs wet-lab or clinical validation before it means anything.

Cite this finding
Permalink
https://cybergenic.im/findings/ce416a4d-0608-4052-86f5-72ae41a349e6
First seen
29 Sep 2026
Prediction registry
Locked 29 Sep 2026, row hash ed5be052272b568022946aec83b61bea (not testable out of sample). How the registry works
BibTeX
@misc{cybergenic_ce416a4d,
  author       = {{Cybergenic}},
  title        = {{SF3B1 and BAP1 mutual exclusivity in melanoma (MSK-IMPACT 50K)}},
  year         = {2026},
  howpublished = {\url{https://cybergenic.im/findings/ce416a4d-0608-4052-86f5-72ae41a349e6}},
  note         = {Research engine finding, first seen 2026-09-29; prediction locked 2026-09-29, registry row hash ed5be052272b568022946aec83b61bea},
  month        = sep
}
See it on the live map Mutations in melanomaBAP1 and SF3B1 in every cohort

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