Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.25 (overall 0.15) | 0.25 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (1168 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress CNTNAP5 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 CNTNAP5 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
- CNTNAP5 in dopamine neurons, braak+0.92 (p 4.0e-4) → +0.11 (p 0.787)receipt 2179
- CNTNAP5 in oligodendrocytes, braak-0.01 (p 0.982) → +0.11 (p 0.784)receipt 2178
Swarm cases
receipt 2179: CNTNAP5 in dopamine neurons, braak
- power
- full sample +0.47 (p 0.051, n 18), 95% CI -0.00 to +0.77. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.41 (p 0.089, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.43 (p 0.077, n 18). could be the mix.
- skeptic
- leave-one-out range +0.38 to +0.56, sign flips 0; without severely affected donors +0.47 (p 0.051, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTNAP5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2178: CNTNAP5 in oligodendrocytes, braak
- power
- full sample -0.04 (p 0.861, n 18), 95% CI -0.50 to +0.43. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.08 (p 0.754, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.10 (p 0.683, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.09, sign flips 4; without severely affected donors -0.04 (p 0.861, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTNAP5 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts