Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.28 (overall 0.18) | 0.28 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in rod photoreceptor cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 52 | 0.82 |
| pathways Reactome | 2 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress SGIP1 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 SGIP1 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
- SGIP1 in dopamine neurons, braak-0.09 (p 0.813) → +0.68 (p 0.046)receipt 2116
- SGIP1 in oligodendrocytes, braak+0.43 (p 0.243) → +0.40 (p 0.285)receipt 2115
Swarm cases
receipt 2116: SGIP1 in dopamine neurons, braak
- power
- full sample +0.26 (p 0.298, n 18), 95% CI -0.24 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.26 (p 0.306, 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 0.450, n 18). could be the mix.
- skeptic
- leave-one-out range +0.17 to +0.40, sign flips 0; without severely affected donors +0.26 (p 0.298, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SGIP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2115: SGIP1 in oligodendrocytes, braak
- power
- full sample +0.33 (p 0.176, n 18), 95% CI -0.16 to +0.69. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.30 (p 0.228, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.41 (p 0.089, n 18). could be the mix.
- skeptic
- leave-one-out range +0.24 to +0.49, sign flips 0; without severely affected donors +0.33 (p 0.176, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SGIP1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts