Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.10 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in ependymal cells | 0.75 |
| chemistry Open Targets | compounds already reach it: cc-401, brimapitide, tanzisertib +2 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 236 | 0.85 |
| pathways Reactome | 4 pathways; mostly iron and oxidative stress | 0.80 |
Knock down and overexpress MAPK10 in astrocytes; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 MAPK10 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- MAPK10 in dopamine neurons, braak+0.06 (p 0.875) → +0.00 (p 1.000)receipt 2687
- MAPK10 in astrocytes, braak+0.00 (p 1.000) → +0.26 (p 0.499)receipt 2686
Swarm cases
receipt 2687: MAPK10 in dopamine neurons, braak
- power
- full sample +0.11 (p 0.671, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.07 (p 0.794, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.03 (p 0.894, n 18). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.27, sign flips 0; without severely affected donors +0.11 (p 0.671, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPK10 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2686: MAPK10 in astrocytes, braak
- power
- full sample +0.16 (p 0.526, n 18), 95% CI -0.33 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.14 (p 0.567, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.29 (p 0.246, n 18). could be the mix.
- skeptic
- leave-one-out range +0.04 to +0.26, sign flips 0; without severely affected donors +0.16 (p 0.526, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPK10 in astrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts