Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in microglia (185 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| 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 | 14 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress ADCY7 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 ADCY7 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
- ADCY7 in microglia, braak+0.25 (p 0.520) → +0.09 (p 0.815)receipt 12855
- ADCY7 in dopamine neurons, braak-0.65 (p 0.058) → -0.38 (p 0.309)receipt 12856
Swarm cases
receipt 12856: ADCY7 in dopamine neurons, braak
- power
- full sample -0.49 (p 0.038, n 18), 95% CI -0.78 to -0.03. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.49 (p 0.038, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.54 (p 0.020, n 18). not the mix.
- skeptic
- leave-one-out range -0.59 to -0.43, sign flips 0; without severely affected donors -0.49 (p 0.038, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ADCY7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12855: ADCY7 in microglia, braak
- power
- full sample +0.23 (p 0.353, n 18), 95% CI -0.26 to +0.63. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.29 (p 0.248, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.27 (p 0.281, n 18). could be the mix.
- skeptic
- leave-one-out range +0.12 to +0.33, sign flips 0; without severely affected donors +0.23 (p 0.353, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ADCY7 in microglia.
case closed: nothing better to follow up.
Receipts
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