Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| 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 | 3 Parkinson's papers of 239 | 0.82 |
| pathways Reactome | 4 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC1A3 in astrocytes; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves evoked dopamine release 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 SLC1A3 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- SLC1A3 in dopamine neurons, braak-0.14 (p 0.716) → +0.08 (p 0.834)receipt 7612
- SLC1A3 in astrocytes, braak-0.54 (p 0.130) → -0.04 (p 0.928)receipt 7611
Swarm cases
receipt 7612: SLC1A3 in dopamine neurons, braak
- power
- full sample -0.04 (p 0.881, n 18), 95% CI -0.50 to +0.44. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.05 (p 0.847, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.03 (p 0.915, n 18). could be the mix.
- skeptic
- leave-one-out range -0.18 to +0.09, sign flips 5; without severely affected donors -0.04 (p 0.881, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC1A3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 7611: SLC1A3 in astrocytes, braak
- power
- full sample -0.23 (p 0.351, n 18), 95% CI -0.63 to +0.26. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.24 (p 0.328, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.24 (p 0.346, n 18). could be the mix.
- skeptic
- leave-one-out range -0.39 to -0.15, sign flips 0; without severely affected donors -0.23 (p 0.351, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC1A3 in astrocytes.
case closed: nothing better to follow up.
Receipts
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