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 oligodendrocyte progenitor cells; strongest in bergmann glia | 0.75 |
| chemistry Open Targets | compounds already reach it: tezampanel anhydrous, tezampanel, selurampanel +1 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 96 | 0.91 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress GRIK4 in oligodendrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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; existing compounds already reach the inhibition arm.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 GRIK4 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- GRIK4 in dopamine neurons, braak-0.33 (p 0.387) → -0.02 (p 0.962)receipt 2817
- GRIK4 in oligodendrocytes, braak-0.06 (p 0.870) → -0.25 (p 0.515)receipt 2816
Swarm cases
receipt 2817: GRIK4 in dopamine neurons, braak
- power
- full sample -0.21 (p 0.393, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.24 (p 0.341, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.53 (p 0.025, n 18). not the mix.
- skeptic
- leave-one-out range -0.31 to -0.11, sign flips 0; without severely affected donors -0.21 (p 0.393, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIK4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2816: GRIK4 in oligodendrocytes, braak
- power
- full sample -0.48 (p 0.044, n 18), 95% CI -0.77 to -0.02. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.48 (p 0.042, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.50 (p 0.033, n 18). not the mix.
- skeptic
- leave-one-out range -0.66 to -0.42, 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 GRIK4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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