Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.52 (overall 0.34) | 0.52 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (5472 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | 17 Parkinson's trials, 1 stopped | 0.95 |
| literature PubMed | 2 Parkinson's papers of 480 | 0.85 |
| pathways Reactome | 1 pathway; mostly growth signalling | 0.60 |
Knock down and overexpress QKI in oligodendrocytes; measure phospho-ERK and phospho-AKT response to GDNF 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
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves phospho-ERK 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 QKI in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; 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
- QKI in oligodendrocytes, braak+0.68 (p 0.042) → +0.25 (p 0.517)receipt 0948
- QKI in dopamine neurons, braak-0.71 (p 0.032) → +0.86 (p 0.003)receipt 0949
Swarm cases
receipt 0949: QKI in dopamine neurons, braak
- power
- full sample +0.08 (p 0.761, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.07 (p 0.781, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.14 (p 0.567, n 18). could be the mix.
- skeptic
- leave-one-out range -0.05 to +0.19, sign flips 2; without severely affected donors +0.08 (p 0.761, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for QKI in dopamine neurons.
case closed: nothing better to follow up.
receipt 0948: QKI in oligodendrocytes, braak
- power
- full sample +0.45 (p 0.063, n 18), 95% CI -0.03 to +0.76. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.42 (p 0.082, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.46 (p 0.054, n 18). could be the mix.
- skeptic
- leave-one-out range +0.38 to +0.60, sign flips 0; without severely affected donors +0.45 (p 0.063, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for QKI in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts