Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.31 (overall 0.49) | 0.31 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in hematopoietic stem cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 197 | 0.91 |
| pathways Reactome | 7 pathways; mostly protein handling | 0.90 |
Knock down and overexpress NRIP1 in microglia; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves proteasome 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 NRIP1 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- NRIP1 in dopamine neurons, braak-0.20 (p 0.613) → +0.31 (p 0.416)receipt 0264
- NRIP1 in microglia, braak+0.27 (p 0.487) → +0.16 (p 0.689)receipt 0263
Swarm cases
receipt 0264: NRIP1 in dopamine neurons, braak
- power
- full sample +0.07 (p 0.774, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.06 (p 0.820, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.06 (p 0.820, n 18). could be the mix.
- skeptic
- leave-one-out range -0.04 to +0.19, sign flips 2; without severely affected donors +0.07 (p 0.774, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NRIP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0263: NRIP1 in microglia, braak
- power
- full sample +0.29 (p 0.246, n 18), 95% CI -0.21 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.29 (p 0.246, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.31 (p 0.214, n 18). could be the mix.
- skeptic
- leave-one-out range +0.19 to +0.42, sign flips 0; without severely affected donors +0.29 (p 0.246, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NRIP1 in microglia.
case closed: nothing better to follow up.
Receipts
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