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, including oligodendrocytes; strongest in b-cells | 0.75 |
| chemistry Open Targets | compounds already reach it: inotuzumab ozogamicin, moxetumomab pasudotox, yttrium y 90 epratuzumab tetraxetan +8 | 0.90 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 8 Parkinson's papers of 2,978 | 0.71 |
| pathways Reactome | 3 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress CD22 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; existing compounds already reach the inhibition arm.
- 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 CD22 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
- CD22 in dopamine neurons, braak-0.04 (p 0.911) → -0.53 (p 0.145)receipt 9348
- CD22 in oligodendrocytes, braak-0.02 (p 0.964) → +0.16 (p 0.685)receipt 9347
Swarm cases
receipt 9348: CD22 in dopamine neurons, braak
- power
- full sample -0.33 (p 0.179, n 18), 95% CI -0.69 to +0.16. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.26 (p 0.294, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.42 (p 0.080, n 18). could be the mix.
- skeptic
- leave-one-out range -0.45 to -0.23, sign flips 0; without severely affected donors -0.33 (p 0.179, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CD22 in dopamine neurons.
case closed: nothing better to follow up.
receipt 9347: CD22 in oligodendrocytes, braak
- power
- full sample +0.00 (p 0.997, n 18), 95% CI -0.47 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.935, 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 -0.16 to +0.12, sign flips 7; without severely affected donors +0.00 (p 0.997, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CD22 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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