Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched in oligodendrocytes (474 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 107 | 0.85 |
| pathways Reactome | 1 pathway; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress FNIP1 in oligodendrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 FNIP1 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- FNIP1 in dopamine neurons, braak+0.00 (p 1.000) → +0.30 (p 0.428)receipt 9518
- FNIP1 in oligodendrocytes, braak+0.36 (p 0.347) → +0.07 (p 0.859)receipt 9517
Swarm cases
receipt 9518: FNIP1 in dopamine neurons, braak
- power
- full sample -0.03 (p 0.908, n 18), 95% CI -0.49 to +0.44. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.814, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.08 (p 0.767, n 18). could be the mix.
- skeptic
- leave-one-out range -0.16 to +0.12, sign flips 5; without severely affected donors -0.03 (p 0.908, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FNIP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 9517: FNIP1 in oligodendrocytes, braak
- power
- full sample +0.17 (p 0.509, n 18), 95% CI -0.33 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.439, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.27 (p 0.273, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.30, sign flips 0; without severely affected donors +0.17 (p 0.509, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FNIP1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts