Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.14 (overall 0.09) | 0.14 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in rod photoreceptor cells | 0.75 |
| chemistry Open Targets | hard to drug | 0.27 |
| 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 vesicle traffic | 1.00 |
Knock down and overexpress MTMR7 in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 MTMR7 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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
- MTMR7 in dopamine neurons, braak+0.40 (p 0.281) → -0.05 (p 0.893)receipt 3109
- MTMR7 in oligodendrocytes, braak-0.11 (p 0.787) → +0.17 (p 0.668)receipt 3108
Swarm cases
receipt 3109: MTMR7 in dopamine neurons, braak
- power
- full sample +0.22 (p 0.379, n 18), 95% CI -0.27 to +0.62. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.26 (p 0.289, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.28 (p 0.269, n 18). could be the mix.
- skeptic
- leave-one-out range +0.12 to +0.36, sign flips 0; without severely affected donors +0.22 (p 0.379, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MTMR7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3108: MTMR7 in oligodendrocytes, braak
- power
- full sample +0.02 (p 0.942, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.962, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.03 (p 0.908, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.17, sign flips 8; without severely affected donors +0.02 (p 0.942, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MTMR7 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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