Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (378 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 | 1 Parkinson's papers of 138 | 0.91 |
| pathways Reactome | 1 pathway; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress CERS1 in astrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 CERS1 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CERS1 in dopamine neurons, braak+0.46 (p 0.209) → +0.10 (p 0.790)receipt 3157
- CERS1 in astrocytes, braak+0.08 (p 0.838) → -0.37 (p 0.329)receipt 3156
Swarm cases
receipt 3157: CERS1 in dopamine neurons, braak
- power
- full sample +0.30 (p 0.221, n 18), 95% CI -0.19 to +0.67. 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: +0.37 (p 0.132, n 18). could be the mix.
- skeptic
- leave-one-out range +0.22 to +0.45, sign flips 0; without severely affected donors +0.30 (p 0.221, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CERS1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3156: CERS1 in astrocytes, braak
- power
- full sample -0.43 (p 0.075, n 18), 95% CI -0.75 to +0.05. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.43 (p 0.075, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.42 (p 0.084, n 18). could be the mix.
- skeptic
- leave-one-out range -0.55 to -0.36, sign flips 0; without severely affected donors -0.43 (p 0.075, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CERS1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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