Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.03 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 436 | 0.85 |
| pathways Reactome | 16 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress TAB2 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 TAB2 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
- TAB2 in dopamine neurons, braak+0.10 (p 0.790) → +0.20 (p 0.613)receipt 6561
- TAB2 in microglia, braak+0.06 (p 0.869) → +0.00 (p 1.000)receipt 6560
Swarm cases
receipt 6561: TAB2 in dopamine neurons, braak
- power
- full sample +0.07 (p 0.794, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.00 (p 0.997, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.04 (p 0.861, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.16, sign flips 2; without severely affected donors +0.07 (p 0.794, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TAB2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6560: TAB2 in microglia, braak
- power
- full sample -0.05 (p 0.834, n 18), 95% CI -0.51 to +0.42. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.735, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.13 (p 0.615, n 18). could be the mix.
- skeptic
- leave-one-out range -0.21 to +0.08, sign flips 4; without severely affected donors -0.05 (p 0.834, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TAB2 in microglia.
case closed: nothing better to follow up.
Receipts
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