Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.04 (overall 0.03) | 0.04 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in bergmann glia | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress ACBD7 in astrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 ACBD7 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- ACBD7 in dopamine neurons, braak-0.20 (p 0.597) → -0.42 (p 0.255)receipt 6912
- ACBD7 in astrocytes, braak-0.03 (p 0.946) → -0.05 (p 0.893)receipt 6911
Swarm cases
receipt 6912: ACBD7 in dopamine neurons, braak
- power
- full sample -0.38 (p 0.125, n 18), 95% CI -0.72 to +0.11. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.36 (p 0.148, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.47 (p 0.047, n 18). not the mix.
- skeptic
- leave-one-out range -0.51 to -0.29, sign flips 0; without severely affected donors -0.38 (p 0.125, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ACBD7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6911: ACBD7 in astrocytes, braak
- power
- full sample -0.11 (p 0.658, n 18), 95% CI -0.55 to +0.37. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.814, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.06 (p 0.800, n 18). could be the mix.
- skeptic
- leave-one-out range -0.24 to -0.02, sign flips 0; without severely affected donors -0.11 (p 0.658, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ACBD7 in astrocytes.
case closed: nothing better to follow up.
Receipts
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