Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (300 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC6A11 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 SLC6A11 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
- SLC6A11 in dopamine neurons, braak-0.18 (p 0.646) → -0.44 (p 0.232)receipt 10246
- SLC6A11 in astrocytes, braak+0.29 (p 0.456) → -0.12 (p 0.767)receipt 10245
Swarm cases
receipt 10246: SLC6A11 in dopamine neurons, braak
- power
- full sample -0.29 (p 0.250, n 18), 95% CI -0.66 to +0.21. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.29 (p 0.243, 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 0.246, n 18). could be the mix.
- skeptic
- leave-one-out range -0.42 to -0.19, sign flips 0; without severely affected donors -0.29 (p 0.250, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC6A11 in dopamine neurons.
case closed: nothing better to follow up.
receipt 10245: SLC6A11 in astrocytes, braak
- power
- full sample +0.04 (p 0.861, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.834, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.07 (p 0.787, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.18, sign flips 2; without severely affected donors +0.04 (p 0.861, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC6A11 in astrocytes.
case closed: nothing better to follow up.
Receipts
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