Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.37 (overall 0.23) | 0.37 |
| cell type Human Protein Atlas | cell type enhanced in microglia (628 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.00 |
| 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 | in no curated pathway | 0.00 |
Knock down and overexpress SH3RF3 in microglia; measure a transcriptome-wide state shift (bulk RNA-seq) and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- 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 SH3RF3 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- SH3RF3 in dopamine neurons, braak-0.54 (p 0.137) → -0.32 (p 0.407)receipt 1882
- SH3RF3 in microglia, braak-0.12 (p 0.768) → -0.42 (p 0.262)receipt 1881
Swarm cases
receipt 1882: SH3RF3 in dopamine neurons, braak
- power
- full sample -0.44 (p 0.069, n 18), 95% CI -0.75 to +0.04. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.44 (p 0.069, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.63 (p 0.0055, n 18). not the mix.
- skeptic
- leave-one-out range -0.54 to -0.37, sign flips 0; without severely affected donors -0.44 (p 0.069, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3RF3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1881: SH3RF3 in microglia, braak
- power
- full sample -0.33 (p 0.185, n 18), 95% CI -0.69 to +0.16. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.39 (p 0.114, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.37 (p 0.130, n 18). could be the mix.
- skeptic
- leave-one-out range -0.44 to -0.23, sign flips 0; without severely affected donors -0.33 (p 0.185, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3RF3 in microglia.
case closed: nothing better to follow up.
Receipts
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