Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.20 (overall 0.12) | 0.20 |
| cell type Human Protein Atlas | cell type enhanced in brain excitatory neurons (60 nCPM) | 1.00 |
| 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 | 3 Parkinson's papers of 549 | 0.82 |
| pathways Reactome | 4 pathways; mostly energy | 0.60 |
Knock down and overexpress ASNS in dopamine neurons; measure oxygen consumption rate and ATP output and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- oxygen consumption rate and ATP output
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 ASNS in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: oxygen consumption rate and ATP output; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- ASNS in dopamine neurons, braak-0.34 (p 0.369) → -0.13 (p 0.738)receipt 2335
Swarm cases
receipt 2335: ASNS in dopamine neurons, braak
- power
- full sample +0.05 (p 0.847, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.09 (p 0.722, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.06 (p 0.807, n 18). could be the mix.
- skeptic
- leave-one-out range -0.09 to +0.15, sign flips 5; without severely affected donors +0.05 (p 0.847, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ASNS in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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