Tandem CRISPR screens identify stress-specific regulators of autophagy. (A) Screening strategy used to identify positive regulators and negative regulators of autophagy pathways. (B) Venn diagrams depict shared and distinct activators or inhibitors among four examined conditions. (C and D) Volcano plots from the four screens. For each gene, the x axis indicates its enrichment or depletion, determined by the mean of all four sgRNAs targeting the gene, in the sorted population compared with the corresponding unsorted population. The y axis represents the statistical significance, as indicated by the FDR-corrected P value. The horizontal dashed line represents an FDR-value threshold of 0.1. Red dots on the graph denote shared regulators across all four conditions, hits specific to different conditions are colored accordingly, and all other genes are represented as gray dots. (E) Gene ontology analysis was performed on screen candidates across the four examined conditions. The top 5 enriched Reactome pathways and corresponding –log10(P values) are shown.