Machine learning tiers PFAS liver hazard, and liver spheroid gene data back it up
- An XGBoost QSAR model trained on high-throughput bioactivity data sorts PFASs into four tiers of liver-related hazard.
- Public transcriptomes from human liver spheroids exposed to 19 PFASs showed response patterns that varied across those tiers.
- Lipid metabolism disruption and cellular stress dominated the signatures, with FABP1, PLIN2 and GDF15 responding across exposures.
💡 Points
Tiers from a QSAR model inherit the weaknesses of their training labels, and high-throughput bioactivity assays rarely capture slow liver injury. PFAS persistence also means spheroid concentrations may sit far from real accumulation, so checking tiers against measured tissue exposure and serum half-life matters. FABP1, PLIN2 and GDF15 look promising as readouts, but stress markers are notoriously non-specific.