Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (1533 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| 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 | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GRM7 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 GRM7 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
- GRM7 in dopamine neurons, braak+0.90 (p 0.001) → +0.29 (p 0.443)receipt 5608
- GRM7 in oligodendrocytes, braak+0.56 (p 0.118) → -0.04 (p 0.927)receipt 5607
Swarm cases
receipt 5608: GRM7 in dopamine neurons, braak
- power
- full sample +0.48 (p 0.046, n 18), 95% CI +0.01 to +0.77. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.48 (p 0.046, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.49 (p 0.039, n 18). not the mix.
- skeptic
- leave-one-out range +0.41 to +0.69, sign flips 0; without severely affected donors +0.48 (p 0.046, n 18). robust.
- cell type
- strongest in OPCs: +0.65 (p 0.0036, n 18) vs +0.48 in dopamine neurons. proposing OPCs.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRM7 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up GRM7 · OPCs · braak: substantia nigra, an independent cohort (already registered)
receipt 5607: GRM7 in oligodendrocytes, braak
- power
- full sample +0.25 (p 0.319, 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 0.319, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.22 (p 0.389, n 18). could be the mix.
- skeptic
- leave-one-out range +0.16 to +0.40, sign flips 0; without severely affected donors +0.25 (p 0.319, n 18). fragile.
- cell type
- strongest in OPCs: +0.65 (p 0.0036, n 18) vs +0.25 in oligodendrocytes. proposing OPCs.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRM7 in oligodendrocytes.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up GRM7 · OPCs · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) +0.50 p 0.076 (needs p < 3.5e-4)
Receipts
loading the receipts