Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (24 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: azd-7687, pradigastat | 0.90 |
| 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 | 3 pathways; mostly other | 0.30 |
Knock down and overexpress DGAT1 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; existing compounds already reach the inhibition arm.
- 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 DGAT1 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
- DGAT1 in oligodendrocytes, braak+0.21 (p 0.586) → -0.26 (p 0.493)receipt 15672
- DGAT1 in dopamine neurons, braak+0.24 (p 0.533) → -0.88 (p 0.002)receipt 15673
Swarm cases
receipt 15673: DGAT1 in dopamine neurons, braak
- power
- full sample -0.34 (p 0.161, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.36 (p 0.148, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.46 (p 0.057, n 18). could be the mix.
- skeptic
- leave-one-out range -0.44 to -0.26, sign flips 0; without severely affected donors -0.34 (p 0.161, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DGAT1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 15672: DGAT1 in oligodendrocytes, braak
- power
- full sample +0.03 (p 0.908, n 18), 95% CI -0.44 to +0.49. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.03 (p 0.908, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.01 (p 0.956, n 18). could be the mix.
- skeptic
- leave-one-out range -0.09 to +0.15, sign flips 5; without severely affected donors +0.03 (p 0.908, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DGAT1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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