Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enriched in oligodendrocytes (3 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: rontalizumab, nadofaragene firadenovec, sifalimumab | 0.81 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 6 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress IFNA2 in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 IFNA2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- IFNA2 in oligodendrocytes, braak+0.16 (p 0.685) → +0.34 (p 0.367)receipt 5267
- IFNA2 in dopamine neurons, braakn/a → n/areceipt 5268
Swarm cases
receipt 5268: IFNA2 in dopamine neurons, braak
- cell type
- IFNA2 is not measured in dopamine neurons; looking elsewhere.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IFNA2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5267: IFNA2 in oligodendrocytes, braak
- power
- full sample +0.25 (p 0.319, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.31 (p 0.211, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.34 (p 0.167, n 18). could be the mix.
- skeptic
- leave-one-out range +0.15 to +0.39, sign flips 0; without severely affected donors +0.25 (p 0.319, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IFNA2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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