Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.90 (overall 0.81) | 0.90 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 1 stopped | 0.20 |
| literature PubMed | 493 Parkinson's papers of 737 | 0.18 |
| pathways Reactome | 4 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress PARK7 in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 PARK7 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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 0.59; 2026-10-25 0.59; 2026-10-24 0.59; 2026-10-23 0.59.
Sealed predictions
- PARK7 in dopamine neurons, braak+0.47 (p 0.197) → -0.26 (p 0.493)receipt 0518
- PARK7 in dopamine neurons, resilience-0.09 (p 0.776) → +0.30 (p 0.241)receipt 0020
- PARK7 in dopamine neurons, braak-0.13 (p 0.418) → -0.26 (p 0.093)receipt 0019
In the sealed studies
- Mitochondrial quality control and Lewy stage: did not hold
Swarm cases
receipt 0518: PARK7 in dopamine neurons, braak
- power
- full sample +0.16 (p 0.526, n 18), 95% CI -0.33 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.16 (p 0.526, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.21 (p 0.408, n 18). could be the mix.
- skeptic
- leave-one-out range +0.04 to +0.29, sign flips 0; without severely affected donors +0.16 (p 0.526, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PARK7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0020: PARK7 in dopamine neurons, resilience
- power
- full sample +0.17 (p 0.400, n 55), 95% CI -0.10 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.15 (p 0.436, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.14 (p 0.487, n 55). could be the mix.
- skeptic
- leave-one-out range +0.09 to +0.27, sign flips 0; without severely affected donors +0.15 (p 0.463, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for PARK7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0019: PARK7 in dopamine neurons, braak
- power
- full sample -0.22 (p 0.049, n 84), 95% CI -0.41 to -0.00. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.22 (p 0.049, n 84). holds up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.17 (p 0.118, n 84). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.19, sign flips 0; without severely affected donors -0.16 (p 0.159, n 75). fragile.
- cell type
- strongest in OPCs: -0.31 (p 0.0043, n 84) vs -0.22 in dopamine neurons. proposing OPCs.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PARK7 in dopamine neurons.
follow-up confirmed in ventral tegmental area.
follow-up PARK7 · OPCs · braak: ventral tegmental area -0.38 p 4.8e-4 (needs p < 0.013)
Receipts
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