Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.61 (overall 0.40) | 0.61 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (1514 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 | 6 Parkinson's papers of 265 | 0.74 |
| pathways Reactome | 4 pathways; mostly other | 0.30 |
Knock down and overexpress CNTN1 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 CNTN1 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
- CNTN1 in dopamine neurons, braak+0.13 (p 0.735) → +0.47 (p 0.197)receipt 0641
- CNTN1 in oligodendrocytes, braak-0.12 (p 0.761) → -0.03 (p 0.944)receipt 0640
Swarm cases
receipt 0641: CNTN1 in dopamine neurons, braak
- power
- full sample +0.35 (p 0.153, n 18), 95% CI -0.14 to +0.70. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.36 (p 0.145, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.33 (p 0.179, n 18). could be the mix.
- skeptic
- leave-one-out range +0.26 to +0.52, sign flips 0; without severely affected donors +0.35 (p 0.153, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTN1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0640: CNTN1 in oligodendrocytes, braak
- power
- full sample +0.04 (p 0.867, n 18), 95% CI -0.43 to +0.50. 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: -0.04 (p 0.867, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.17, sign flips 5; without severely affected donors +0.04 (p 0.867, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CNTN1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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