Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in pericytes | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| 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 protein handling | 0.90 |
Knock down and overexpress ADAMTS4 in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves proteasome activity 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 ADAMTS4 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- ADAMTS4 in dopamine neurons, braak-0.32 (p 0.400) → -0.17 (p 0.656)receipt 6004
- ADAMTS4 in oligodendrocytes, braak-0.33 (p 0.393) → -0.11 (p 0.787)receipt 6003
Swarm cases
receipt 6004: ADAMTS4 in dopamine neurons, braak
- power
- full sample -0.29 (p 0.246, n 18), 95% CI -0.67 to +0.21. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.22 (p 0.379, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.19 (p 0.455, n 18). could be the mix.
- skeptic
- leave-one-out range -0.38 to -0.19, sign flips 0; without severely affected donors -0.29 (p 0.246, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ADAMTS4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6003: ADAMTS4 in oligodendrocytes, braak
- power
- full sample -0.14 (p 0.573, n 18), 95% CI -0.57 to +0.35. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.17 (p 0.509, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.11 (p 0.671, n 18). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.02, sign flips 0; without severely affected donors -0.14 (p 0.573, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ADAMTS4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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