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, including oligodendrocytes; strongest in neutrophils | 0.75 |
| chemistry Open Targets | compounds already reach it: gimeracil, eniluracil | 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 | 1 pathway; mostly other | 0.30 |
Knock down and overexpress DPYD 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 DPYD 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
- DPYD in oligodendrocytes, braak+0.06 (p 0.888) → +0.42 (p 0.262)receipt 14487
- DPYD in dopamine neurons, braak+0.43 (p 0.249) → +0.08 (p 0.839)receipt 14488
Swarm cases
receipt 14488: DPYD in dopamine neurons, braak
- power
- full sample +0.21 (p 0.393, n 18), 95% CI -0.28 to +0.62. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.455, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.22 (p 0.379, n 18). could be the mix.
- skeptic
- leave-one-out range +0.14 to +0.39, sign flips 0; without severely affected donors +0.21 (p 0.393, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DPYD in dopamine neurons.
case closed: nothing better to follow up.
receipt 14487: DPYD in oligodendrocytes, braak
- power
- full sample +0.21 (p 0.408, n 18), 95% CI -0.29 to +0.61. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.408, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.47 (p 0.047, n 18). not the mix.
- skeptic
- leave-one-out range +0.10 to +0.39, sign flips 0; without severely affected donors +0.21 (p 0.408, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DPYD in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts