Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.57 (overall 0.35) | 0.57 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in neutrophils | 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 | 4 Parkinson's papers of 333 | 0.79 |
| pathways Reactome | 1 pathway; mostly iron and oxidative stress | 0.80 |
Knock down and overexpress MAP4K4 in oligodendrocytes; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron 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
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves reactive oxygen species (CellROX) 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 MAP4K4 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; 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
- MAP4K4 in oligodendrocytes, braak+0.52 (p 0.148) → -0.16 (p 0.682)receipt 0886
- MAP4K4 in dopamine neurons, braak+0.39 (p 0.304) → +0.00 (p 1.000)receipt 0887
Swarm cases
receipt 0887: MAP4K4 in dopamine neurons, braak
- power
- full sample +0.20 (p 0.418, n 18), 95% CI -0.29 to +0.61. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.418, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.25 (p 0.319, n 18). could be the mix.
- skeptic
- leave-one-out range +0.10 to +0.32, sign flips 0; without severely affected donors +0.20 (p 0.418, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAP4K4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0886: MAP4K4 in oligodendrocytes, braak
- power
- full sample +0.08 (p 0.748, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.09 (p 0.722, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.28 (p 0.261, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.21, sign flips 4; without severely affected donors +0.08 (p 0.748, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAP4K4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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