Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.20 (overall 0.15) | 0.20 |
| cell type Human Protein Atlas | cell type enhanced in microglia (702 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: vatalanib, axatilimab, imc-cs4 +18 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 90 Parkinson's papers of 3,002 | 0.41 |
| pathways Reactome | 3 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress CSF1R 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; existing compounds already reach the inhibition arm.
- 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 CSF1R 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
- CSF1R in dopamine neurons, braak-0.23 (p 0.560) → +0.09 (p 0.820)receipt 2196
- CSF1R in microglia, braak-0.29 (p 0.449) → -0.15 (p 0.702)receipt 2195
Swarm cases
receipt 2196: CSF1R in dopamine neurons, braak
- power
- full sample -0.08 (p 0.741, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.07 (p 0.787, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.06 (p 0.820, n 18). could be the mix.
- skeptic
- leave-one-out range -0.17 to +0.04, sign flips 3; without severely affected donors -0.08 (p 0.741, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CSF1R in dopamine neurons.
case closed: nothing better to follow up.
receipt 2195: CSF1R in microglia, braak
- power
- full sample -0.22 (p 0.389, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.21 (p 0.408, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.11 (p 0.677, n 18). could be the mix.
- skeptic
- leave-one-out range -0.34 to -0.11, sign flips 0; without severely affected donors -0.22 (p 0.389, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CSF1R in microglia.
case closed: nothing better to follow up.
Receipts
loading the receipts