Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in vascular smooth muscle 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCNAB1 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 KCNAB1 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
- KCNAB1 in oligodendrocytes, braak+0.07 (p 0.859) → -0.63 (p 0.071)receipt 14034
- KCNAB1 in dopamine neurons, braak-0.08 (p 0.840) → -0.05 (p 0.893)receipt 14035
Swarm cases
receipt 14035: KCNAB1 in dopamine neurons, braak
- power
- full sample -0.09 (p 0.735, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.715, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.19 (p 0.455, n 18). could be the mix.
- skeptic
- leave-one-out range -0.20 to +0.04, sign flips 3; 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 KCNAB1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 14034: KCNAB1 in oligodendrocytes, braak
- power
- full sample -0.19 (p 0.455, n 18), 95% CI -0.60 to +0.31. 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: -0.38 (p 0.118, n 18). could be the mix.
- skeptic
- leave-one-out range -0.29 to -0.08, sign flips 0; without severely affected donors -0.19 (p 0.455, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNAB1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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