Extended Data Fig. 5: Bulk RNA-seq analysis between untreated Brca2^null and Brca1^null tumors yields gene expression programs related to adaptive and innate immunity enriched in Brca2^null tumors.

a, Heatmap displaying all 6,881 genes significantly differentially expressed (FDR < 0.05) between untreated Brca2^null and Brca1^null murine tumors from the 4T1 model. Data show drastic gene expression changes upon Brca2 inactivation. P-values calculated from two-sided differential expression analysis using DESeq2 (Wald test) and corrected for multiple testing using the Benjamini-Hochberg method. b, Pathway analysis on genes from a using GO pathways. Top enriched pathways in either Brca2^null or Brca1^null tumors are shown. Color gradient of red to purple indicates decreasing adjusted p-value; circle size indicates number of genes in pathway. GeneRatio on x-axis indicates number of significantly differentially expressed genes from RNA-seq overlapping with genes in each pathway. P-values for overlap between input genes and pathway genesets calculated via two-sided hypergeometric test and corrected for multiple comparisons using the Benjamini Hochberg method. c, Heatmap for genes significantly differentially expressed in a associated with interferon gamma signaling between Brca2^null and Brca1^null murine tumors from the 4T1 model. d, Heatmap displaying for genes significantly differentially expressed in a associated with T cell activation between Brca2^null and Brca1^null murine tumors from the 4T1 model. e, Heatmap for genes significantly differentially expressed in a associated with antigen presentation between Brca2^null and Brca1^null murine tumors from the 4T1 model. f, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the Kurozumi Response to Cytolytic Virus pathway, evaluated using GSEA (FDR P <= 0.05). g, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the Reactome chemokines pathway, evaluated using GSEA (FDR P <= 0.05).h, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the NK-mediated cytotoxicity pathway, evaluated using GSEA (FDR P <= 0.05). For c-h, P-values calculated from two-sided differential expression analysis using DESeq2 (Wald test) and correct for multiple testing using the Benjamini-Hochberg method. i, Heatmap of mean log-normalized expression of differentially expressed genes for genes promoting immune activity/evasion in between Brca1^null and Brca2^null deficient cell lines in vitro. For all GSEA analyses, p-values calculated using two-sided pre-ranked analysis using log fold changes as input.

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