Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched in astrocytes (106 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.50 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 176 | 0.82 |
| pathways Reactome | 3 pathways; mostly energy | 0.60 |
Knock down and overexpress ALDOC in astrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves oxygen consumption rate 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 ALDOC in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- ALDOC in astrocytes, braak-0.26 (p 0.502) → -0.58 (p 0.101)receipt 10898
- ALDOC in dopamine neurons, braak+0.66 (p 0.051) → +0.47 (p 0.199)receipt 10899
Swarm cases
receipt 10899: ALDOC in dopamine neurons, braak
- power
- full sample +0.66 (p 0.0030, n 18), 95% CI +0.28 to +0.86. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.67 (p 0.0024, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.74 (p 5.0e-4, n 18). not the mix.
- skeptic
- leave-one-out range +0.62 to +0.80, sign flips 0; without severely affected donors +0.66 (p 0.0030, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ALDOC in dopamine neurons.
case closed: nothing better to follow up.
receipt 10898: ALDOC in astrocytes, braak
- power
- full sample -0.43 (p 0.077, n 18), 95% CI -0.75 to +0.05. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.50 (p 0.035, n 18). holds up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.48 (p 0.046, n 18). not the mix.
- skeptic
- leave-one-out range -0.59 to -0.36, sign flips 0; without severely affected donors -0.43 (p 0.077, n 18). robust.
- cell type
- strongest in dopamine neurons: +0.66 (p 0.0030, n 18) vs -0.43 in astrocytes. proposing dopamine neurons.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ALDOC in astrocytes.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up ALDOC · dopamine neurons · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) +0.43 p 0.131 (needs p < 2.0e-4)
Receipts
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