Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (28 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: rwj-67657, regorafenib, losmapimod | 1.00 |
| trials ClinicalTrials.gov | 6 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 13 pathways; mostly protein handling | 0.90 |
Knock down and overexpress MAPK11 in astrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves proteasome activity 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 MAPK11 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- MAPK11 in astrocytes, braak-0.08 (p 0.840) → -0.45 (p 0.227)receipt 8878
- MAPK11 in dopamine neurons, braak+0.04 (p 0.912) → -0.36 (p 0.347)receipt 8879
Swarm cases
receipt 8879: MAPK11 in dopamine neurons, braak
- power
- full sample -0.11 (p 0.677, n 18), 95% CI -0.55 to +0.38. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.10 (p 0.696, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.27 (p 0.281, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to -0.01, sign flips 0; without severely affected donors -0.11 (p 0.677, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPK11 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8878: MAPK11 in astrocytes, braak
- power
- full sample -0.16 (p 0.526, n 18), 95% CI -0.58 to +0.33. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.515, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.21 (p 0.393, n 18). could be the mix.
- skeptic
- leave-one-out range -0.30 to -0.06, 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 MAPK11 in astrocytes.
case closed: nothing better to follow up.
Receipts
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