Journal: Science Advances
Article Title: Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth
doi: 10.1126/sciadv.adk1057
Figure Lengend Snippet: ( A ) The algorithm ranked all the 4293 FDR-approved drugs, clinical trial drugs, and preclinical tool compounds based on the predicted effectiveness on treating sPTB. ( B ) The predicted scores and rank percentiles for drugs that had been used or are under clinical trials to treat sPTB. ( C ) The top 50 highly ranked drugs displayed significant functional associations with the preterm birth genes identified in this study, where the bottom ranked 50 drugs exhibited the least functional associations with the preterm birth genes from this study. ( D ) The top 10 candidate drugs predicted by our model for experimental validation. ( E ) The effects on increasing or decrease myometrial cell contractility determined by the collagen gel contraction assay when treating primary human uterine smooth muscle cells (HUtSMCs) with the identified small molecules. The treatment effectiveness was determined in the contractile (stimulated by OXY) or in the quiescence state (PBS). P values were derived from Wilcoxon rank sum tests. ( F ) The dose-response curve for the top candidate drug RKI-1447 in quiescent HUtSMCs. The inset shows the dose-response curve of HUtSMCs treated with different concentrations of RKI-1447. ( G ) Studying the effects of RKI-1447 on the multiscale network identified its functional associations with many muscle proteins with the strongest association with MYLK. ( H ) Docking analysis between RKI-1447 and MYLK confirmed their binding affinity.
Article Snippet: Primary HUtSMCs were purchased from PromoCells (catalog no. C-12575, Thermo Fisher Scientific, MA).
Techniques: Functional Assay, Collagen Gel Contraction Assay, Derivative Assay, Binding Assay