Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.38 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in myonuclei | 0.75 |
| chemistry Open Targets | compounds already reach it: pinacidil, minoxidil | 1.00 |
| 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 ABCC9 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 ABCC9 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
- ABCC9 in dopamine neurons, braak+0.07 (p 0.855) → +0.41 (p 0.277)receipt 0687
- ABCC9 in astrocytes, braak+0.48 (p 0.187) → -0.59 (p 0.098)receipt 0686
Swarm cases
receipt 0687: ABCC9 in dopamine neurons, braak
- power
- full sample +0.24 (p 0.332, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.25 (p 0.310, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.23 (p 0.351, n 18). could be the mix.
- skeptic
- leave-one-out range +0.16 to +0.40, sign flips 0; without severely affected donors +0.24 (p 0.332, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ABCC9 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0686: ABCC9 in astrocytes, braak
- power
- full sample -0.20 (p 0.424, n 18), 95% CI -0.61 to +0.29. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.27 (p 0.281, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.12 (p 0.640, n 18). could be the mix.
- skeptic
- leave-one-out range -0.31 to -0.08, sign flips 0; without severely affected donors -0.20 (p 0.424, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ABCC9 in astrocytes.
case closed: nothing better to follow up.
Receipts
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