Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (52 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 2 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress CTSO in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR 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
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves IL-1β 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 CTSO in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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
- CTSO in dopamine neurons, braak+0.12 (p 0.749) → +0.39 (p 0.299)receipt 11331
- CTSO in oligodendrocytes, braak+0.48 (p 0.186) → -0.45 (p 0.227)receipt 11330
Swarm cases
receipt 11331: CTSO in dopamine neurons, braak
- power
- full sample +0.31 (p 0.211, n 18), 95% CI -0.18 to +0.68. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.35 (p 0.159, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.32 (p 0.194, n 18). could be the mix.
- skeptic
- leave-one-out range +0.23 to +0.45, sign flips 0; without severely affected donors +0.31 (p 0.211, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CTSO in dopamine neurons.
case closed: nothing better to follow up.
receipt 11330: CTSO in oligodendrocytes, braak
- power
- full sample +0.11 (p 0.664, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.664, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.22 (p 0.389, n 18). could be the mix.
- skeptic
- leave-one-out range +0.00 to +0.24, sign flips 1; without severely affected donors +0.11 (p 0.664, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CTSO in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts