Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.04 (overall 0.02) | 0.04 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in renal collecting duct intercalated cells | 0.75 |
| 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 | 4 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress MRPS5 in oligodendrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) 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
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 MRPS5 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); 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
- MRPS5 in dopamine neurons, braak+0.57 (p 0.108) → +0.26 (p 0.493)receipt 7427
- MRPS5 in oligodendrocytes, braak+0.21 (p 0.591) → +0.58 (p 0.102)receipt 7426
Swarm cases
receipt 7427: MRPS5 in dopamine neurons, braak
- power
- full sample +0.40 (p 0.097, n 18), 95% CI -0.08 to +0.73. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.40 (p 0.103, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.41 (p 0.095, n 18). could be the mix.
- skeptic
- leave-one-out range +0.34 to +0.58, sign flips 0; without severely affected donors +0.40 (p 0.097, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MRPS5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 7426: MRPS5 in oligodendrocytes, braak
- power
- full sample +0.40 (p 0.103, n 18), 95% CI -0.09 to +0.73. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.39 (p 0.114, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.49 (p 0.041, n 18). not the mix.
- skeptic
- leave-one-out range +0.30 to +0.52, sign flips 0; without severely affected donors +0.40 (p 0.103, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MRPS5 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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