Cybergenic
All findings

BRAF + TSC1

BRAF and TSC1 co-occurrence in non-small cell lung cancer (OrigiMed China)

Strengthened: held up under a stratified controlCo-occurrence · Evidence: pattern across patients, not yet tested within subtypes

DataOrigiMed China (2020) · Non-small cell lung cancer · 2,016 tumours · both altered in 4 (0.2 expected if independent)

Engine's conclusion

Strengthened. Significant, with a real effect in a consistent direction, and it still holds when tumours are compared only within the same tumour type (and within the same molecular subtype, wherever this cancer's subtypes are known in the data). No artifact check failed.

A well-studied pair (1,028 papers): on the map it is known biology, a positive control rather than an overlooked discovery.

Not called novel: a PubTator3 search finds 3 papers naming both BRAF and TSC1 in non-small cell lung cancer in the title or abstract. See the PubTator3 search.

Statistical support49%Significance (FDR q)0.003Signal (x)12%Efficacy (y)2%

Signal (x) is the corrected significance on the map's scale, discounted from 26% to 12% because the cohort-composition confound is not yet controlled. Efficacy (y) is credibility times actionability.

Structure & site3D structure: AlphaFold

These genes are altered together more often than chance would predict.

Primary site

Lung

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

Drag to rotate. Dark marks the hotspot residues on the predicted fold. For a fuller read of this same model, open the interactive structure workbench for this protein on Nanoverse (a companion site we also run), which maps its binding pockets, per-region confidence, and the likely effect of a mutation.

BRAFOncogeneApproved therapy

B-Raf proto-oncogene kinase

Oncogene: when altered it gets stuck ON and drives growth.

Serine/threonine kinase downstream of RAS; V600E targeted by BRAF+MEK inhibitor combinations.

Pathway
RTK to RAS to MAPK
Hotspots in 3D
V600 · K601 · G469
Drives
Melanoma, Thyroid, Colorectal
BRAF mutations in non-small cell lung cancer →BRAF co-mutations by tumour type →Other findings with BRAF →

No structure profile is curated for this gene.

TSC1Gene

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

TSC1 mutations in non-small cell lung cancer →TSC1 co-mutations by tumour type →Other findings with TSC1 →

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)
5 × 10-6
Effect (log₂ odds ratio)
5.6
Papers
1,028
Abstracts naming both
3
Trials
0
Contingency table: the source of the q2,016 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 stateTSC1 alteredTSC1 wild-type
BRAF altered436
BRAF wild-type51,971

both 4 (expected 0.2 if independent) · BRAF-only 36 · TSC1-only 5 · neither 1,971

Sources
cBioPortal / OrigiMed China (2020)Genome NexusOmniPath / Reactome / STRINGUCSC XenaOpen TargetsPubTator3NIH iCiteEurope PMCClinicalTrials.gov
Anytime-valid evidence (e-value)e = 9.1

Substantial evidence. Below 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)9%

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.

BRAFOncogeneTSC1VemurafenibDabrafenib
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 for the BRAF–TSC1 population-level co-occurrence is residual molecular-subtype or lineage composition in this NSCLC cohort, rather than demonstrated within-tumour cooperation. This predicts that the association will weaken or disappear after adjustment for sufficiently detailed molecular subtype in an independent, subtype-annotated cohort.

Argument strength (model self-report)15%
After adversarial review15%
The argument
  1. 1The signal is statistically strong after burden-aware testing and multiple-testing correction, with a very large within-lineage estimated odds ratio (2^5.6), but it is based on only four double-altered tumours. Thus it merits follow-up without establishing a biological interaction.E1E19
  2. 2Residual molecular-subtype composition is the leading explanation: the adjustment recorded lineage but did not resolve molecular subtype, and the prior NSCLC BRAF–TSC1 corpus finding explicitly proposed unresolved subtype composition. The lead therefore CONVERGES with that prior finding and with the prior NSCLC BRAF–KRAS subtype concern; the pancreatic BRAF–KRAS and melanoma BRAF–PTEN findings are related context, not direct replication of this pair.E2E16E18E15E17
  3. 3Among alternatives, a cohort-specific artifact or winner's-curse effect ranks next because the association has not recurred in another independent patient source. A shared upstream driver is possible but not specifically supported here; deterministic co-amplification is also unsubstantiated because the evidence gives neither alteration classes nor genomic proximity. Genuine within-tumour cooperation ranks last as an interpretation of this population-level pattern.E1E3E13E14
  4. 4The supplied paper abstracts do not establish a BRAF–TSC1 relationship: the tuberous-sclerosis case report concerns TSC and a lung manifestation, while the colorectal review discusses broad pathway dysregulation; neither studies this gene pair. The co-mention summary likewise does not show that the pair was studied mechanistically. This lack of pair-specific evidence strengthens the under-explored status of the lead, not a cooperation claim.E9E10E11
What would confirm or refute it

Test the subtype-composition hypothesis in an independent NSCLC cohort with detailed molecular-subtype annotation: estimate the BRAF–TSC1 association within subtypes and using a subtype-adjusted model, while accounting for alteration class and tumour-level alteration burden. Persistence within well-powered subtype strata would weaken the leading explanation. To earn a within-tumour cooperation claim, additionally use clonal or single-cell profiling to verify both alterations in the same tumour cells and a functional co-dependency experiment comparing single- versus double-altered models.

Strongest competing explanation (model)

The subtype explanation is a testable best guess, not a demonstrated cause. The very large estimated effect comes from just four co-altered tumours, the subtype adjustment is incomplete, and the signal is confined so far to one patient source; cohort composition or a winner's-curse/data artifact could therefore account for it. There is no cited paper that studies BRAF and TSC1 together, so a within-tumour mechanism is unearned.

Adversarial review (second model pass)

Weakest link: Residual subtype composition is only a plausible explanation, not demonstrated: subtype is unresolved, the signal rests on four co-altered tumors in one cohort, and no independent replication tests the prediction.

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/4f673113-a959-4bfc-8af8-59bb4e7514f4
First seen
29 Sep 2026
Prediction registry
Locked 29 Sep 2026, row hash 25434de14bad8faeaf268d146b88d54c (not testable out of sample). How the registry works
BibTeX
@misc{cybergenic_4f673113,
  author       = {{Cybergenic}},
  title        = {{BRAF and TSC1 co-occurrence in non-small cell lung cancer (OrigiMed China)}},
  year         = {2026},
  howpublished = {\url{https://cybergenic.im/findings/4f673113-a959-4bfc-8af8-59bb4e7514f4}},
  note         = {Research engine finding, first seen 2026-09-29; prediction locked 2026-09-29, registry row hash 25434de14bad8faeaf268d146b88d54c},
  month        = sep
}
See it on the live map Mutations in non-small cell lung cancerBRAF and TSC1 in every cohort

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