Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched, including microglia; strongest in b-cells | 0.75 |
| chemistry Open Targets | compounds already reach it: ianalumab | 0.81 |
| 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 | 3 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress TNFRSF13C 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 TNFRSF13C 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
- TNFRSF13C in microglia, braak+0.14 (p 0.714) → +0.17 (p 0.665)receipt 7203
- TNFRSF13C in dopamine neurons, braak-0.18 (p 0.646) → +0.41 (p 0.269)receipt 7204
Swarm cases
receipt 7204: TNFRSF13C in dopamine neurons, braak
- power
- full sample -0.06 (p 0.820, 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 0.709, 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 -0.22 to +0.07, sign flips 4; without severely affected donors -0.06 (p 0.820, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNFRSF13C in dopamine neurons.
case closed: nothing better to follow up.
receipt 7203: TNFRSF13C in microglia, braak
- power
- full sample +0.16 (p 0.526, n 18), 95% CI -0.33 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.956, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.05 (p 0.847, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.34, sign flips 0; without severely affected donors +0.16 (p 0.526, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNFRSF13C in microglia.
case closed: nothing better to follow up.
Receipts
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