Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in microglia (605 nCPM) | 1.00 |
| 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 | 1 pathway; mostly immune signalling | 0.90 |
Knock down and overexpress LY86 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 LY86 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
- LY86 in microglia, braak+0.64 (p 0.063) → -0.08 (p 0.842)receipt 10063
- LY86 in dopamine neurons, braak-0.06 (p 0.877) → -0.08 (p 0.838)receipt 10064
Swarm cases
receipt 10064: LY86 in dopamine neurons, braak
- power
- full sample -0.07 (p 0.787, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.11 (p 0.677, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.14 (p 0.573, n 18). could be the mix.
- skeptic
- leave-one-out range -0.23 to +0.01, sign flips 1; without severely affected donors -0.07 (p 0.787, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LY86 in dopamine neurons.
case closed: nothing better to follow up.
receipt 10063: LY86 in microglia, braak
- power
- full sample +0.17 (p 0.504, n 18), 95% CI -0.32 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.677, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.20 (p 0.424, 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 0.504, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LY86 in microglia.
case closed: nothing better to follow up.
Receipts
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