Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.09 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enriched in astrocytes (6365 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 | 12 Parkinson's papers of 229 | 0.66 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC1A2 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 SLC1A2 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
- SLC1A2 in dopamine neurons, braak+0.11 (p 0.773) → +0.35 (p 0.360)receipt 3011
- SLC1A2 in astrocytes, braak+0.26 (p 0.493) → +0.22 (p 0.570)receipt 3010
Swarm cases
receipt 3011: SLC1A2 in dopamine neurons, braak
- power
- full sample +0.29 (p 0.243, n 18), 95% CI -0.20 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.29 (p 0.235, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.29 (p 0.235, n 18). could be the mix.
- skeptic
- leave-one-out range +0.21 to +0.45, sign flips 0; without severely affected donors +0.29 (p 0.243, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC1A2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3010: SLC1A2 in astrocytes, braak
- power
- full sample +0.30 (p 0.232, n 18), 95% CI -0.20 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.31 (p 0.204, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.31 (p 0.204, n 18). could be the mix.
- skeptic
- leave-one-out range +0.21 to +0.40, sign flips 0; without severely affected donors +0.30 (p 0.232, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC1A2 in astrocytes.
case closed: nothing better to follow up.
Receipts
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