Extended Data Fig. 10: Evaluation of the effects of MOA compounds on LPS responses in PBMCs (continued).
From: Scalable, compressed phenotypic screening using pooled perturbations
a. Annotation of NK cell cNMF GEP modules from LPS+control condition. b. Bar plot of compounds with the strongest effects on LPS response in each cell type. c. Divergent effects on LPS GEP7 in monocytes by two pyruvate dehydrogenase kinase inhibitors where BX-912 is a positive potentiator and AZD7545 is a positive interferer. Two-sided Mann-Whitney U test without correction was performed to test score differences (Methods). All the box plots indicate 25th percentile at the bottom, median in the middle and 75th percentile at the top. Whiskers are drawn to the farthest datapoints within 1.5* interquartile range from the nearest hinge. d. ML298 Hydrochloride as a representative compound with pleiotropic effects across cell types in both IFNβ (right) and LPS (left) stimulation conditions. Module scores were normalized against median in DMSO+stimulation condition in each comparison. Two-sided Mann-Whitney U test without multiple hypothesis correction was performed to test score differences (Methods). All the box plots indicate 25th percentile at the bottom, median in the middle and 75th percentile at the top. Whiskers are drawn to the farthest datapoints within 1.5* interquartile range from the nearest hinge. e. Ruxolitinib as a positive interferer of LPS-GEP3 in CD8 T cells. Two-sided Mann-Whitney U test without correction was performed to test score differences (Methods). All the box plots indicate 25th percentile at the bottom, median in the middle and 75th percentile at the top. Whiskers are drawn to the farthest datapoints within 1.5* interquartile range from the nearest hinge. f. Evaluation of CS LPS response module (B cell GEP3) in Ruxolitinib-only perturbation. Two-sided Mann-Whitney U test without correction was performed to test score differences (Methods). All the box plots indicate 25th percentile at the bottom, median in the middle and 75th percentile at the top. Whiskers are drawn to the farthest datapoints within 1.5* interquartile range from the nearest hinge. Despite a statistically insignificant difference in monocytes between DMSO-only and DMSO + LPS treated groups, the large shift between the module scores warrants the inclusion of Ruxolitinib’s effect as an example of a positive potentiator in this cell type.
