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, including microglia; strongest in neutrophils | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.40 |
| 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 iron and oxidative stress | 0.80 |
Knock down and overexpress DPEP2 in microglia; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron 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
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves reactive oxygen species (CellROX) 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 DPEP2 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; 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
- DPEP2 in dopamine neurons, braak-0.45 (p 0.224) → -0.45 (p 0.222)receipt 16830
- DPEP2 in microglia, braak+0.06 (p 0.888) → -0.33 (p 0.386)receipt 16829
Swarm cases
receipt 16830: DPEP2 in dopamine neurons, braak
- power
- full sample -0.46 (p 0.056, n 18), 95% CI -0.76 to +0.01. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.47 (p 0.047, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.56 (p 0.017, n 18). not the mix.
- skeptic
- leave-one-out range -0.56 to -0.39, sign flips 0; without severely affected donors -0.46 (p 0.056, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DPEP2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 16829: DPEP2 in microglia, braak
- power
- full sample -0.18 (p 0.476, n 18), 95% CI -0.60 to +0.31. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.19 (p 0.460, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.11 (p 0.664, n 18). could be the mix.
- skeptic
- leave-one-out range -0.30 to -0.05, sign flips 0; without severely affected donors -0.18 (p 0.476, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DPEP2 in microglia.
case closed: nothing better to follow up.
Receipts
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