Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched, including oligodendrocytes; strongest in prostatic glandular cells | 0.75 |
| chemistry Open Targets | compounds already reach it: huj591 111in, mln-2704, huj591 177lu +3 | 1.00 |
| 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 | 1 pathway; mostly energy | 0.60 |
Knock down and overexpress FOLH1 in oligodendrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves oxygen consumption rate 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 FOLH1 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- FOLH1 in dopamine neurons, braak+0.37 (p 0.334) → +0.20 (p 0.615)receipt 3934
- FOLH1 in oligodendrocytes, braak+0.14 (p 0.714) → +0.37 (p 0.331)receipt 3933
Swarm cases
receipt 3934: FOLH1 in dopamine neurons, braak
- power
- full sample +0.27 (p 0.273, n 18), 95% CI -0.22 to +0.66. 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: +0.36 (p 0.142, n 18). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.41, sign flips 0; without severely affected donors +0.27 (p 0.273, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FOLH1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3933: FOLH1 in oligodendrocytes, braak
- power
- full sample +0.27 (p 0.273, n 18), 95% CI -0.22 to +0.66. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.28 (p 0.265, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.24 (p 0.341, n 18). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.41, sign flips 0; without severely affected donors +0.27 (p 0.273, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FOLH1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts