Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.67 (overall 0.56) | 0.67 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| 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 | 7 Parkinson's papers of 269 | 0.73 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress PTPA in a dopamine neuron, astrocyte and microglia tri-culture; measure a transcriptome-wide state shift (bulk RNA-seq) and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 PTPA in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.58; 2026-10-25 0.58; 2026-10-24 0.58; 2026-10-23 0.58.
Sealed predictions
- PTPA in dopamine neurons, braak-0.11 (p 0.787) → -0.48 (p 0.188)receipt 0581
- PTPA in dopamine neurons, resilience-0.25 (p 1.000) → -0.20 (p 0.379)receipt 0122
- PTPA in dopamine neurons, braak-0.16 (p 0.307) → -0.18 (p 0.260)receipt 0121
Swarm cases
receipt 0581: PTPA in dopamine neurons, braak
- power
- full sample -0.34 (p 0.164, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.31 (p 0.207, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.30 (p 0.232, n 18). could be the mix.
- skeptic
- leave-one-out range -0.46 to -0.26, sign flips 0; without severely affected donors -0.34 (p 0.164, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTPA in dopamine neurons.
case closed: nothing better to follow up.
receipt 0122: PTPA in dopamine neurons, resilience
- power
- full sample -0.14 (p 0.474, n 55), 95% CI -0.39 to +0.13. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: -0.14 (p 0.474, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.15 (p 0.436, n 55). could be the mix.
- skeptic
- leave-one-out range -0.23 to -0.07, sign flips 0; without severely affected donors -0.16 (p 0.417, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for PTPA in dopamine neurons.
case closed: nothing better to follow up.
receipt 0121: PTPA in dopamine neurons, braak
- power
- full sample -0.17 (p 0.130, n 84), 95% CI -0.37 to +0.05. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.15 (p 0.175, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.10 (p 0.358, n 84). could be the mix.
- skeptic
- leave-one-out range -0.20 to -0.14, sign flips 0; without severely affected donors -0.13 (p 0.269, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTPA in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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