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 enhanced, including oligodendrocytes; strongest in epicardial cells | 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 | 3 Parkinson's papers of 274 | 0.82 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCNJ10 in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 KCNJ10 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- KCNJ10 in dopamine neurons, braak+0.82 (p 0.006) → +0.40 (p 0.291)receipt 3103
- KCNJ10 in oligodendrocytes, braak-0.31 (p 0.414) → -0.12 (p 0.759)receipt 3102
Swarm cases
receipt 3103: KCNJ10 in dopamine neurons, braak
- power
- full sample +0.48 (p 0.044, n 18), 95% CI +0.02 to +0.77. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.58 (p 0.011, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.61 (p 0.0069, n 18). not the mix.
- skeptic
- leave-one-out range +0.41 to +0.61, sign flips 0; without severely affected donors +0.48 (p 0.044, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNJ10 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3102: KCNJ10 in oligodendrocytes, braak
- power
- full sample -0.28 (p 0.258, n 18), 95% CI -0.66 to +0.21. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.31 (p 0.207, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.36 (p 0.148, n 18). could be the mix.
- skeptic
- leave-one-out range -0.47 to -0.22, sign flips 0; without severely affected donors -0.28 (p 0.258, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNJ10 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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