Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched in astrocytes (345 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| 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 | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC25A18 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 SLC25A18 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
- SLC25A18 in dopamine neurons, braak-0.04 (p 0.928) → -0.64 (p 0.063)receipt 12735
- SLC25A18 in astrocytes, braak-0.22 (p 0.576) → +0.56 (p 0.116)receipt 12734
Swarm cases
receipt 12735: SLC25A18 in dopamine neurons, braak
- power
- full sample -0.34 (p 0.164, n 18), 95% CI -0.70 to +0.15. 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
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.31 (p 0.204, n 18). could be the mix.
- skeptic
- leave-one-out range -0.48 to -0.24, sign flips 0; without severely affected donors -0.34 (p 0.164, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC25A18 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12734: SLC25A18 in astrocytes, braak
- power
- full sample +0.19 (p 0.444, n 18), 95% CI -0.30 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.444, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.54 (p 0.022, n 18). not the mix.
- skeptic
- leave-one-out range +0.09 to +0.35, sign flips 0; without severely affected donors +0.19 (p 0.444, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC25A18 in astrocytes.
case closed: nothing better to follow up.
Receipts
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