Single-cell perturbation atlas of PTB prevention candidate drugs

Preterm birth (PTB) is the leading cause of mortality in children under five, yet effective preventive therapies are lacking. PTB’s multifactorial nature, as well as the high cost and ethical challenges of pregnancy clinical trials, hinder drug development efforts. Meanwhile, targeting immune pathways that regulate labor timing is emerging as a promising preventive strategy. We present Simulated Immune Modeling of Clinical Outcomes (SIMCO), a prediction ensemble that integrates single-cell immune perturbation modeling with outcome prediction to rapidly evaluate PTB prevention candidate drugs. To train SIMCO, we generated a mass cytometry perturbation atlas of 218 million leukocytes, capturing drug effects on specific cell types and signaling pathways that differed between pregnant and non-pregnant individuals. SIMCO accurately recapitulated the single-cell modulation induced by nine repurposed candidate drugs. When applied to an independent longitudinal pregnancy cohort, SIMCO simulated..., , # Data from: Single-cell perturbation atlas of PTB prevention candidate drugs Dataset DOI: [10.5061/dryad.sqv9s4ngm](10.5061/dryad.sqv9s4ngm) ## Description of the data and file structure From 19 individuals (n = 11 pregnant individuals, PV01-PV11, and n = 8 non-pregnant individuals, HV04-HV11), whole blood was exposed to nine candidate drugs for preterm birth. Candidate drugs are abbreviated as follows: chlorthalidone (CHT), maprotiline (MAP), metformin (MF), lansoprazole (LPZ), pravastatin (PRA), rifabutin (RIF), salicylic acid (SA), salicylic acid + lansoprazole (SALPZ), and 5-methyltetrahydrofolate (THF). Dimethyl sulfoxide (DMSO) was used in triplicate (DMSO1, DMSO2, DMSO3) as no-drug control. After 1 h of drug exposure, the in vitro cultured whole blood was stimulated with LPS (50 ng/ml), IFNα (50 ng/ml), IL-33 (50 ng/ml), GM-CSF (50 ng/ml), TNFα (50 ng/ml), a cocktail of IL-2, IL-4, and IL-6 (each 50 ng/ml), PI (0.5×), or left unstimulated for 2 h at 37 °C and 5 % CO~2~ in a h...,