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 late spermatids | 0.75 |
| chemistry Open Targets | hard to drug | 0.27 |
| 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 | 6 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress SH3GL3 in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 SH3GL3 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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
- SH3GL3 in oligodendrocytes, braak-0.11 (p 0.784) → +0.43 (p 0.253)receipt 16298
- SH3GL3 in dopamine neurons, braak-0.29 (p 0.449) → +0.41 (p 0.273)receipt 16299
Swarm cases
receipt 16299: SH3GL3 in dopamine neurons, braak
- power
- full sample +0.08 (p 0.748, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.00 (p 0.990, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.02 (p 0.942, n 18). could be the mix.
- skeptic
- leave-one-out range -0.05 to +0.17, sign flips 4; without severely affected donors +0.08 (p 0.748, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3GL3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 16298: SH3GL3 in oligodendrocytes, braak
- power
- full sample +0.10 (p 0.690, n 18), 95% CI -0.38 to +0.54. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.08 (p 0.767, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.12 (p 0.627, n 18). could be the mix.
- skeptic
- leave-one-out range +0.00 to +0.26, sign flips 1; without severely affected donors +0.10 (p 0.690, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3GL3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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