Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in neutrophils | 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 | 1 Parkinson's papers of 307 | 0.91 |
| pathways Reactome | 6 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress ITGAX 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 ITGAX 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
- ITGAX in dopamine neurons, braak-0.61 (p 0.078) → -0.11 (p 0.787)receipt 6014
- ITGAX in microglia, braak+0.41 (p 0.273) → +0.03 (p 0.946)receipt 6013
Swarm cases
receipt 6014: ITGAX in dopamine neurons, braak
- power
- full sample -0.38 (p 0.120, n 18), 95% CI -0.72 to +0.11. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.40 (p 0.101, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.40 (p 0.101, n 18). could be the mix.
- skeptic
- leave-one-out range -0.47 to -0.30, sign flips 0; without severely affected donors -0.38 (p 0.120, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ITGAX in dopamine neurons.
case closed: nothing better to follow up.
receipt 6013: ITGAX in microglia, braak
- power
- full sample +0.26 (p 0.306, n 18), 95% CI -0.24 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.418, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.27 (p 0.273, n 18). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.44, sign flips 0; without severely affected donors +0.26 (p 0.306, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ITGAX in microglia.
case closed: nothing better to follow up.
Receipts
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