Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.57 from other evidence | 0.00 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: metformin, me-344, metformin hydrochloride | 1.00 |
| trials ClinicalTrials.gov | 4 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 4 Parkinson's papers of 40 | 0.79 |
| pathways Reactome | 2 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress NDUFB7 in a dopamine neuron, astrocyte and microglia tri-culture; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) 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; existing compounds already reach the inhibition arm.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 NDUFB7 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); 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 0.57; 2026-10-25 0.57; 2026-10-24 0.57; 2026-10-23 0.57.
Sealed predictions
- NDUFB7 in dopamine neurons, braak+0.37 (p 0.324) → +0.03 (p 0.946)receipt 0573
- NDUFB7 in dopamine neurons, resilience+0.37 (p 0.256) → -0.22 (p 0.374)receipt 0108
- NDUFB7 in dopamine neurons, braak-0.01 (p 0.927) → +0.01 (p 0.940)receipt 0107
Swarm cases
receipt 0573: NDUFB7 in dopamine neurons, braak
- power
- full sample +0.24 (p 0.328, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.403, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.30 (p 0.225, n 18). could be the mix.
- skeptic
- leave-one-out range +0.14 to +0.41, sign flips 0; without severely affected donors +0.24 (p 0.328, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFB7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0108: NDUFB7 in dopamine neurons, resilience
- power
- full sample +0.03 (p 0.866, n 55), 95% CI -0.23 to +0.30. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.04 (p 0.833, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.04 (p 0.850, n 55). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.09, sign flips 3; without severely affected donors +0.03 (p 0.887, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for NDUFB7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0107: NDUFB7 in dopamine neurons, braak
- power
- full sample +0.01 (p 0.942, n 84), 95% CI -0.21 to +0.22. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.01 (p 0.913, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.02 (p 0.840, n 84). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.04, sign flips 20; without severely affected donors +0.01 (p 0.918, n 75). fragile.
- cell type
- strongest in astrocytes: +0.42 (p 6.6e-5, n 84) vs +0.01 in dopamine neurons. proposing astrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFB7 in dopamine neurons.
follow-up registered; not confirmed in ventral tegmental area.
follow-up NDUFB7 · astrocytes · braak: ventral tegmental area +0.31 p 0.0047 (needs p < 0.0031)
Receipts
loading the receipts