Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in myonuclei | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| 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 | 4 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress SLC8A3 in oligodendrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 SLC8A3 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- SLC8A3 in dopamine neurons, braak+0.25 (p 0.517) → +0.06 (p 0.870)receipt 4932
- SLC8A3 in oligodendrocytes, braak-0.09 (p 0.821) → -0.12 (p 0.767)receipt 4931
Swarm cases
receipt 4932: SLC8A3 in dopamine neurons, braak
- power
- full sample +0.09 (p 0.735, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.00 (p 0.997, 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 0.894, n 18). could be the mix.
- skeptic
- leave-one-out range -0.02 to +0.21, sign flips 1; without severely affected donors +0.09 (p 0.735, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC8A3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4931: SLC8A3 in oligodendrocytes, braak
- power
- full sample -0.15 (p 0.544, n 18), 95% CI -0.58 to +0.34. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.15 (p 0.544, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.13 (p 0.615, n 18). could be the mix.
- skeptic
- leave-one-out range -0.29 to -0.03, sign flips 0; without severely affected donors -0.15 (p 0.544, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC8A3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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