Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (28 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: atacicept, sibeprenlimab | 0.81 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 172 | 0.91 |
| pathways Reactome | 2 pathways; mostly other | 0.30 |
Knock down and overexpress TNFSF13 in astrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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; existing compounds already reach the inhibition arm.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 TNFSF13 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- TNFSF13 in dopamine neurons, braak-0.78 (p 0.014) → +0.01 (p 0.982)receipt 8501
- TNFSF13 in astrocytes, braak-0.12 (p 0.750) → +0.45 (p 0.219)receipt 8500
Swarm cases
receipt 8501: TNFSF13 in dopamine neurons, braak
- power
- full sample -0.26 (p 0.306, n 18), 95% CI -0.65 to +0.24. 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: -0.20 (p 0.418, n 18). could be the mix.
- skeptic
- leave-one-out range -0.36 to -0.16, sign flips 0; without severely affected donors -0.26 (p 0.306, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNFSF13 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8500: TNFSF13 in astrocytes, braak
- power
- full sample +0.15 (p 0.544, n 18), 95% CI -0.34 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.13 (p 0.609, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.02 (p 0.942, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.29, sign flips 0; without severely affected donors +0.15 (p 0.544, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNFSF13 in astrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts