Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.20 (overall 0.13) | 0.20 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in pericytes | 0.75 |
| chemistry Open Targets | compounds already reach it: nintedanib esylate, tivozanib, tandutinib +42 | 1.00 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 28 Parkinson's papers of 1,473 | 0.56 |
| pathways Reactome | 6 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress PDGFRB in astrocytes; measure phospho-ERK and phospho-AKT response to GDNF 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
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves phospho-ERK 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 PDGFRB in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; 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
- PDGFRB in astrocytes, braak+0.62 (p 0.078) → +0.13 (p 0.732)receipt 2249
- PDGFRB in dopamine neurons, braak-0.47 (p 0.197) → -0.33 (p 0.380)receipt 2250
Swarm cases
receipt 2250: PDGFRB in dopamine neurons, braak
- power
- full sample -0.39 (p 0.109, n 18), 95% CI -0.73 to +0.09. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.38 (p 0.125, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.54 (p 0.021, n 18). not the mix.
- skeptic
- leave-one-out range -0.48 to -0.31, sign flips 0; without severely affected donors -0.39 (p 0.109, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PDGFRB in dopamine neurons.
case closed: nothing better to follow up.
receipt 2249: PDGFRB in astrocytes, braak
- power
- full sample +0.35 (p 0.150, n 18), 95% CI -0.14 to +0.70. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.35 (p 0.150, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.32 (p 0.201, n 18). could be the mix.
- skeptic
- leave-one-out range +0.25 to +0.48, sign flips 0; without severely affected donors +0.35 (p 0.150, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PDGFRB in astrocytes.
case closed: nothing better to follow up.
Receipts
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