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, 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 | 2 Parkinson's papers of 248 | 0.85 |
| pathways Reactome | 2 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress SIGLEC9 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 SIGLEC9 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
- SIGLEC9 in microglia, braak-0.16 (p 0.685) → -0.11 (p 0.775)receipt 8838
- SIGLEC9 in dopamine neurons, braak-0.63 (p 0.068) → -0.11 (p 0.787)receipt 8839
Swarm cases
receipt 8839: SIGLEC9 in dopamine neurons, braak
- power
- full sample -0.24 (p 0.328, n 18), 95% CI -0.64 to +0.25. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.23 (p 0.351, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.33 (p 0.176, n 18). could be the mix.
- skeptic
- leave-one-out range -0.43 to -0.17, sign flips 0; without severely affected donors -0.24 (p 0.328, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SIGLEC9 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8838: SIGLEC9 in microglia, braak
- power
- full sample -0.09 (p 0.715, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.07 (p 0.774, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.13 (p 0.603, n 18). could be the mix.
- skeptic
- leave-one-out range -0.23 to +0.01, sign flips 3; without severely affected donors -0.09 (p 0.715, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SIGLEC9 in microglia.
case closed: nothing better to follow up.
Receipts
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