Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.51 (overall 0.31) | 0.51 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in neutrophils | 0.75 |
| chemistry Open Targets | hard to drug | 0.00 |
| 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 | in no curated pathway | 0.00 |
Knock down and overexpress ZNF608 in oligodendrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 ZNF608 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- ZNF608 in oligodendrocytes, braak-0.22 (p 0.576) → +0.23 (p 0.549)receipt 1210
- ZNF608 in dopamine neurons, braak+0.25 (p 0.520) → +0.17 (p 0.663)receipt 1211
Swarm cases
receipt 1211: ZNF608 in dopamine neurons, braak
- power
- full sample +0.28 (p 0.254, n 18), 95% CI -0.21 to +0.66. 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
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.35 (p 0.153, n 18). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.41, sign flips 0; without severely affected donors +0.28 (p 0.254, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ZNF608 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1210: ZNF608 in oligodendrocytes, braak
- power
- full sample -0.04 (p 0.881, n 18), 95% CI -0.50 to +0.44. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.800, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.04 (p 0.874, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.10, sign flips 4; without severely affected donors -0.04 (p 0.881, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ZNF608 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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