Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in papillary tip epithelial cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 27 | 0.85 |
| pathways Reactome | 2 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress B3GALT4 in microglia; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) activity 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 B3GALT4 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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
- B3GALT4 in dopamine neurons, braak-0.31 (p 0.416) → -0.53 (p 0.146)receipt 5511
- B3GALT4 in microglia, braak-0.33 (p 0.390) → +0.30 (p 0.435)receipt 5510
Swarm cases
receipt 5511: B3GALT4 in dopamine neurons, braak
- power
- full sample -0.46 (p 0.054, n 18), 95% CI -0.76 to +0.01. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.45 (p 0.062, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.46 (p 0.052, n 18). could be the mix.
- skeptic
- leave-one-out range -0.57 to -0.38, sign flips 0; without severely affected donors -0.46 (p 0.054, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for B3GALT4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5510: B3GALT4 in microglia, 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: -0.03 (p 0.901, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.06 (p 0.814, n 18). could be the mix.
- skeptic
- leave-one-out range -0.20 to +0.05, sign flips 3; 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 B3GALT4 in microglia.
case closed: nothing better to follow up.
Receipts
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