Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.88 (overall 0.80) | 0.88 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 131 Parkinson's papers of 183 | 0.36 |
| pathways Reactome | 2 pathways; mostly protein handling | 0.90 |
Knock down and overexpress FBXO7 in a dopamine neuron, astrocyte and microglia tri-culture; measure proteasome activity and the load of ubiquitinated protein and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves proteasome activity by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of FBXO7 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.
Sealed predictions
- FBXO7 in dopamine neurons, braak-0.01 (p 0.982) → +0.73 (p 0.026)receipt 0519
- FBXO7 in dopamine neurons, resilience+0.33 (p 0.194) → +0.61 (p 0.056)receipt 0022
- FBXO7 in dopamine neurons, braak+0.04 (p 0.792) → +0.43 (p 0.004)receipt 0021
In the sealed studies
- Mitochondrial quality control and Lewy stage: did not hold
Swarm cases
receipt 0519: FBXO7 in dopamine neurons, braak
- power
- full sample +0.20 (p 0.418, n 18), 95% CI -0.29 to +0.61. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.27 (p 0.285, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.37 (p 0.135, n 18). could be the mix.
- skeptic
- leave-one-out range +0.10 to +0.36, sign flips 0; without severely affected donors +0.20 (p 0.418, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FBXO7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0022: FBXO7 in dopamine neurons, resilience
- power
- full sample +0.39 (p 0.046, n 55), 95% CI +0.14 to +0.60. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: +0.38 (p 0.053, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.51 (p 0.0091, n 55). not the mix.
- skeptic
- leave-one-out range +0.34 to +0.42, sign flips 0; without severely affected donors +0.43 (p 0.034, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for FBXO7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0021: FBXO7 in dopamine neurons, braak
- power
- full sample +0.21 (p 0.056, n 84), 95% CI -0.01 to +0.41. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.15 (p 0.175, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.14 (p 0.196, n 84). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.25, sign flips 0; without severely affected donors +0.24 (p 0.039, n 75). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FBXO7 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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