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 in oligodendrocytes (260 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| 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 | 2 pathways; mostly other | 0.30 |
Knock down and overexpress HBS1L in oligodendrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 HBS1L in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- HBS1L in dopamine neurons, braak-0.23 (p 0.551) → +0.20 (p 0.613)receipt 10533
- HBS1L in oligodendrocytes, braak-0.08 (p 0.838) → +0.58 (p 0.101)receipt 10532
Swarm cases
receipt 10533: HBS1L in dopamine neurons, braak
- power
- full sample +0.05 (p 0.840, n 18), 95% CI -0.43 to +0.51. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.02 (p 0.942, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.07 (p 0.781, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.16, sign flips 3; without severely affected donors +0.05 (p 0.840, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HBS1L in dopamine neurons.
case closed: nothing better to follow up.
receipt 10532: HBS1L in oligodendrocytes, braak
- power
- full sample +0.27 (p 0.285, n 18), 95% CI -0.23 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.17 (p 0.493, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.15 (p 0.561, n 18). could be the mix.
- skeptic
- leave-one-out range +0.19 to +0.47, sign flips 0; without severely affected donors +0.27 (p 0.285, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HBS1L in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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