Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 2 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress ORMDL3 in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 ORMDL3 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- ORMDL3 in dopamine neurons, braak-0.20 (p 0.597) → -0.91 (p 5.9e-4)receipt 10947
Swarm cases
receipt 10947: ORMDL3 in dopamine neurons, braak
- power
- full sample -0.49 (p 0.040, n 18), 95% CI -0.78 to -0.03. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.53 (p 0.024, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.65 (p 0.0033, n 18). not the mix.
- skeptic
- leave-one-out range -0.63 to -0.42, sign flips 0; without severely affected donors -0.49 (p 0.040, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ORMDL3 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
loading the receipts