Fig. 2: Identification of compound hits that phenopush cells from the acute hypoxic state towards the chronic hypoxic state.

a Overview of AH-to-CH phenopushing screening and hit-calling framework. N: Normoxia. AH: Acute hypoxia (1 d). CH: Chronic hypoxia (6 d). D: Distance from the phenotypic profile of a perturbation (a given compound at a given dose) to the centroid of the phenotypic profiles of CH DMSO controls. θ: Angle of deviation from the phenotypic profile of a perturbation relative to the centroid of the phenotypic profiles of CH DMSO controls. The cell icons: Created in BioRender. Wu, A. (2025) https://BioRender.com/q85j552. b Summary of geometric hit calls in the primary screen. Scatter plot and density map for distance (x-axis) and direction (y-axis) of bioactive compounds. Red solid line and dotted line show cutoffs for distance and angle, respectively. Vehicle (DMSO) controls in N, AH, and CH are shown for reference. Bioactive non-hit compounds (black dots), hits (red dots), and four hit examples (large red dots) are shown. c Screening funnel for AH-to-CH phenopushing hits. d Representative images for DMSO under N, AH, or CH compared to hit examples (highlighted in b) in AH (Temsirolimus, Deforolimus, KU-0063794, WYE-354). The experiment was independently repeated three times with similar results. Source data are provided as a Source Data file.