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 | 3 Parkinson's papers of 68 | 0.82 |
| pathways Reactome | 5 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress NDUFAB1 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 NDUFAB1 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
- NDUFAB1 in dopamine neurons, braak+0.31 (p 0.421) → +0.32 (p 0.407)receipt 0572
- NDUFAB1 in dopamine neurons, resilience-0.17 (p 0.581) → -0.35 (p 0.192)receipt 0106
- NDUFAB1 in dopamine neurons, braak+0.06 (p 0.713) → -0.02 (p 0.914)receipt 0105
Swarm cases
receipt 0572: NDUFAB1 in dopamine neurons, braak
- power
- full sample +0.25 (p 0.319, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.24 (p 0.332, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.25 (p 0.310, n 18). could be the mix.
- skeptic
- leave-one-out range +0.17 to +0.40, sign flips 0; without severely affected donors +0.25 (p 0.319, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFAB1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0106: NDUFAB1 in dopamine neurons, resilience
- power
- full sample -0.27 (p 0.171, n 55), 95% CI -0.50 to -0.00. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.25 (p 0.207, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.24 (p 0.230, n 55). could be the mix.
- skeptic
- leave-one-out range -0.39 to -0.20, sign flips 0; without severely affected donors -0.28 (p 0.160, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for NDUFAB1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0105: NDUFAB1 in dopamine neurons, braak
- power
- full sample +0.03 (p 0.795, n 84), 95% CI -0.19 to +0.24. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.01 (p 0.952, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.03 (p 0.752, n 84). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.06, sign flips 3; without severely affected donors +0.03 (p 0.806, n 75). fragile.
- cell type
- strongest in oligodendrocytes: +0.35 (p 0.0013, n 84) vs +0.03 in dopamine neurons. proposing oligodendrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFAB1 in dopamine neurons.
follow-up registered; not confirmed in ventral tegmental area.
follow-up NDUFAB1 · oligodendrocytes · braak: ventral tegmental area +0.25 p 0.026 (needs p < 0.0033)
Receipts
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