Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (259 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 | 1 Parkinson's papers of 139 | 0.91 |
| pathways Reactome | 4 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress MTMR2 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 MTMR2 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
- MTMR2 in dopamine neurons, braak+0.55 (p 0.122) → +0.58 (p 0.101)receipt 4087
- MTMR2 in oligodendrocytes, braak+0.59 (p 0.096) → +0.52 (p 0.149)receipt 4086
Swarm cases
receipt 4087: MTMR2 in dopamine neurons, braak
- power
- full sample +0.45 (p 0.060, n 18), 95% CI -0.02 to +0.76. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.44 (p 0.067, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.51 (p 0.030, n 18). not the mix.
- skeptic
- leave-one-out range +0.38 to +0.55, sign flips 0; without severely affected donors +0.45 (p 0.060, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MTMR2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4086: MTMR2 in oligodendrocytes, braak
- power
- full sample +0.44 (p 0.064, n 18), 95% CI -0.03 to +0.75. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.50 (p 0.034, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.51 (p 0.029, n 18). not the mix.
- skeptic
- leave-one-out range +0.38 to +0.61, sign flips 0; without severely affected donors +0.44 (p 0.064, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MTMR2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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