Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.77 (overall 0.47) | 0.77 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in retinal amacrine cells | 0.75 |
| 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 16 | 0.91 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress IGSF9B 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 IGSF9B 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
- IGSF9B in dopamine neurons, braak+0.16 (p 0.680) → -0.83 (p 0.005)receipt 0293
- IGSF9B in oligodendrocytes, braak-0.28 (p 0.459) → -0.40 (p 0.285)receipt 0292
Swarm cases
receipt 0293: IGSF9B in dopamine neurons, braak
- power
- full sample -0.42 (p 0.080, n 18), 95% CI -0.74 to +0.05. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.43 (p 0.072, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.58 (p 0.011, n 18). not the mix.
- skeptic
- leave-one-out range -0.57 to -0.35, sign flips 0; without severely affected donors -0.42 (p 0.080, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IGSF9B in dopamine neurons.
case closed: nothing better to follow up.
receipt 0292: IGSF9B in oligodendrocytes, braak
- power
- full sample -0.27 (p 0.273, n 18), 95% CI -0.66 to +0.22. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.28 (p 0.269, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.43 (p 0.075, n 18). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.18, 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 IGSF9B in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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