Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in rod photoreceptor cells | 0.75 |
| chemistry Open Targets | compounds already reach it: oleclumab | 0.81 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 3 Parkinson's papers of 521 | 0.82 |
| pathways Reactome | 4 pathways; mostly energy | 0.60 |
Knock down and overexpress NT5E in oligodendrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves oxygen consumption rate 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 NT5E in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- NT5E in dopamine neurons, braak+0.33 (p 0.386) → +0.14 (p 0.722)receipt 4815
- NT5E in oligodendrocytes, braak+0.11 (p 0.787) → -0.14 (p 0.718)receipt 4814
Swarm cases
receipt 4815: NT5E in dopamine neurons, braak
- power
- full sample +0.30 (p 0.232, n 18), 95% CI -0.20 to +0.67. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.31 (p 0.211, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.532, n 18). could be the mix.
- skeptic
- leave-one-out range +0.22 to +0.46, sign flips 0; without severely affected donors +0.30 (p 0.232, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NT5E in dopamine neurons.
case closed: nothing better to follow up.
receipt 4814: NT5E in oligodendrocytes, braak
- power
- full sample +0.01 (p 0.976, n 18), 95% CI -0.46 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.01 (p 0.956, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.17 (p 0.504, n 18). could be the mix.
- skeptic
- leave-one-out range -0.12 to +0.12, sign flips 7; without severely affected donors +0.01 (p 0.976, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NT5E in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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