Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in b-cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| 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 immune signalling | 0.90 |
Knock down and overexpress HLA-DOB in astrocytes; measure IL-1β and TNF release and surface HLA-DR 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.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves IL-1β 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 HLA-DOB in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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
- HLA-DOB in dopamine neurons, braak-0.47 (p 0.197) → +0.07 (p 0.857)receipt 13288
- HLA-DOB in astrocytes, braak-0.21 (p 0.586) → +0.17 (p 0.668)receipt 13287
Swarm cases
receipt 13288: HLA-DOB in dopamine neurons, braak
- power
- full sample -0.30 (p 0.232, n 18), 95% CI -0.67 to +0.20. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.28 (p 0.254, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.58 (p 0.012, n 18). not the mix.
- skeptic
- leave-one-out range -0.40 to -0.21, sign flips 0; without severely affected donors -0.30 (p 0.232, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HLA-DOB in dopamine neurons.
case closed: nothing better to follow up.
receipt 13287: HLA-DOB in astrocytes, braak
- power
- full sample -0.15 (p 0.544, n 18), 95% CI -0.58 to +0.34. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.33 (p 0.188, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.35 (p 0.150, n 18). could be the mix.
- skeptic
- leave-one-out range -0.27 to -0.04, sign flips 0; without severely affected donors -0.15 (p 0.544, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HLA-DOB in astrocytes.
case closed: nothing better to follow up.
Receipts
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