Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.25 (overall 0.16) | 0.25 |
| cell type Human Protein Atlas | cell type enhanced, including brain inhibitory neurons; strongest in retinal ganglion cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 6 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress ROBO2 in dopamine neurons; measure phospho-ERK and phospho-AKT response to GDNF and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 ROBO2 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- ROBO2 in dopamine neurons, braak+0.77 (p 0.014) → +0.15 (p 0.697)receipt 2177
Swarm cases
receipt 2177: ROBO2 in dopamine neurons, braak
- power
- full sample +0.47 (p 0.048, n 18), 95% CI +0.01 to +0.77. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.48 (p 0.045, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.53 (p 0.024, n 18). not the mix.
- skeptic
- leave-one-out range +0.40 to +0.62, sign flips 0; without severely affected donors +0.47 (p 0.048, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ROBO2 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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