Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (65 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 5 Parkinson's papers of 57 | 0.76 |
| pathways Reactome | 1 pathway; mostly protein handling | 0.90 |
Knock down and overexpress DCAF17 in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 DCAF17 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- DCAF17 in oligodendrocytes, braak+0.71 (p 0.032) → -0.12 (p 0.749)receipt 11818
- DCAF17 in dopamine neurons, braak+0.41 (p 0.272) → -0.12 (p 0.750)receipt 11819
Swarm cases
receipt 11819: DCAF17 in dopamine neurons, braak
- power
- full sample +0.18 (p 0.487, n 18), 95% CI -0.32 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.23 (p 0.355, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.25 (p 0.315, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.28, sign flips 0; without severely affected donors +0.18 (p 0.487, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DCAF17 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11818: DCAF17 in oligodendrocytes, braak
- power
- full sample +0.53 (p 0.025, n 18), 95% CI +0.08 to +0.80. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.58 (p 0.011, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.59 (p 0.0096, n 18). not the mix.
- skeptic
- leave-one-out range +0.45 to +0.66, sign flips 0; without severely affected donors +0.53 (p 0.025, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DCAF17 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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