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 microglia; strongest in neutrophils | 0.75 |
| chemistry Open Targets | a small-molecule pocket: interferon gamma-1b | 0.60 |
| trials ClinicalTrials.gov | 3 Parkinson's trials, 1 stopped | 0.73 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 4 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress IFNGR2 in microglia; measure IL-1β and TNF release and surface HLA-DR and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- 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 IFNGR2 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- IFNGR2 in dopamine neurons, braak+0.44 (p 0.233) → +0.27 (p 0.485)receipt 15666
- IFNGR2 in microglia, braak+0.48 (p 0.190) → -0.06 (p 0.877)receipt 15665
Swarm cases
receipt 15666: IFNGR2 in dopamine neurons, braak
- power
- full sample +0.26 (p 0.298, n 18), 95% CI -0.24 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.444, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.22 (p 0.374, n 18). could be the mix.
- skeptic
- leave-one-out range +0.14 to +0.35, sign flips 0; without severely affected donors +0.26 (p 0.298, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IFNGR2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 15665: IFNGR2 in microglia, braak
- power
- full sample +0.17 (p 0.493, n 18), 95% CI -0.32 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.17 (p 0.493, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.17 (p 0.509, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.31, sign flips 0; without severely affected donors +0.17 (p 0.493, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IFNGR2 in microglia.
case closed: nothing better to follow up.
Receipts
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