Extended Data Fig. 3: Identification of hit compounds and target genes.
From: Phenotypic landscape of intestinal organoid regeneration
a, Top, compound abundance in the library and hit list. Bottom, distribution of enrichment scores for targets of the screen hits. Every data point represents a unique target-gene–modality pair. b, Heat map showing phenotypic signatures for genes with a compound coverage of at least three compounds per gene. Heat map rows marked by arrowheads show compounds used as representative conditions per target. Senr, target enrichment score (see a). c, Left, contingency table for two-sided Fischer’s exact test; right, bar plot and box plot of P-value distributions in the indicated compound condition groups. High conf. hits, high-confidence hits. In the box plot, boxes show quartile ranges; whiskers show value intervals with excluded outliers; centre lines show median values. n = 699, 167 and 29 unique target genes for non-hits, other hits and high-confidence hits respectively. d, Enrichment and false discovery rate for functional annotation enrichments reported by the STRING database tool (https://string-db.org/) for the list of 29 target genes (e). e, Top left, Venn diagram showing the distribution of target genes by compound coverage. Main panel, network of functional interactions for the set of genes with high-compound coverage and hitlist specific enrichment. Edges show interactions known in the STRING database; thickness and line type represent the STRING combined score (see network key); nodes show unique target genes; node outlines show phenotypic clusters with the highest enrichment; circles indicate groups of similar functional annotations. f, Enrichment of KEGG terms (percentage of genes annotated with KEGG terms) in conditions from the hit list where the highest enriched phenotype is either ‘regenerative’ or ‘enterocyst’. Values are sorted by corresponding P-values (two-sided test based on hypergeometric distribution with Bonferroni correction). n = 59 and 61 genes for the enterocyst and regenerative phenotypes, respectively.
